Patent Grant
6962989
Certain products and by-products of naturally-occurring metabolic processes in cells have utility in a wide array of industries, including the food, feed, cosmetics, and pharmaceutical industries. These molecules, collectively termed ‘fine chemicals’, include organic acids, both proteinogenic and non-proteinogenic amino acids, nucleotides and nucleosides, lipids and fatty acids, diols, carbohydrates, aromatic compounds, vitamins and cofactors, and enzymes. Their production is most conveniently performed through the large-scale culture of bacteria developed to produce and secrete large quantities of one or more desired molecules. One particularly useful organism for this purpose is Corynebacterium glutamicum, a gram positive, nonpathogenic bacterium. Through strain selection, a number of mutant strains have been developed which produce an array of desirable compounds. However, selection of strains improved for the production of a particular molecule is a time-consuming and difficult process.
The invention provides novel bacterial nucleic acid molecules which have a variety of uses. These uses include the identification of microorganisms which can be used to produce fine chemicals, the modulation of fine chemical production in C. glutamicum or related bacteria, the typing or identification of C. glutamicum or related bacteria, as reference points for mapping the C. glutamicum genome, and as markers for transformation. These novel nucleic acid molecules encode proteins, referred to herein as marker and fine chemical production (MCP) proteins.
C. glutamicum is a gram positive, aerobic bacterium which is commonly used in industry for the large-scale production of a variety of fine chemicals, and also for the degradation of hydrocarbons (such as in petroleum spills) and for the oxidation of terpenoids. The MCP nucleic acid molecules of the invention, therefore, can be used to identify microorganisms which can be used to produce fine chemicals, e.g., by fermentation processes. Modulation of the expression of the MCP nucleic acids of the invention, or modification of the sequence of the MCP nucleic acid molecules of the invention, can be used to modulate the production of one or more fine chemicals from a microorganism (e.g., to improve the yield or production of one or more fine chemicals from a Corynebacterium or Brevibacterium species).
The MCP nucleic acids of the invention may also be used to identify an organism as being Corynebacterium glutamicum or a close relative thereof, or to identify the presence of C. glutamicum or a relative thereof in a mixed population of microorganisms. The invention provides the nucleic acid sequences of a number of C. glutamicum genes; by probing the extracted genomic DNA of a culture of a unique or mixed population of microorganisms under stringent conditions with a probe spanning a region of a C. glutamicum gene which is unique to this organism, one can ascertain whether this organism is present. Although Corynebacterium glutamicum itself is nonpathogenic, it is related to species pathogenic in humans, such as Corynebacterium diphtheriae (the causative agent of diphtheria); the detection of such organisms is of significant clinical relevance.
The MCP nucleic acid molecules of the invention may also serve as reference points for mapping of the C. glutamicum genome, or of genomes of related organisms. Similarly, these molecules, or variants or portions thereof, may serve as markers for genetically engineered Corynebacterium or Brevibacterium species.
The MCP proteins encoded by the novel nucleic acid molecules of the invention may be involved, for example, in the direct or indirect production of one or more fine chemicals from C. glutamicum. The MCP proteins of the invention may also participate in the degradation of hydrocarbons or the oxidation of terpenoids. These proteins may also be utilized for the identification of Corynebacterium glutamicum or organisms related to C. glutamicum; the presence of an MCP protein specific to C. glutamicum and related species in a mixture of proteins may indicate the presence of one of these bacteria in the sample. Further, these MCP proteins may have homologues in plants or animals which are involved in a disease state or condition; these proteins thus may serve as useful pharmaceutical targets for drug screening and the development of therapeutic compounds.
Given the availability of cloning vectors for use in Corynebacterium glutamicum, such as those disclosed in Sinskey et al., U.S. Pat. No. 4,649,119, and techniques for genetic manipulation of C. glutamicum and the related Brevibacterium species (e.g., lactofermentum) (Yoshihama et al, J. Bacteriol. 162: 591-597 (1985); Katsumata et al., J. Bacteriol. 159: 306-311 (1984); and Santamaria et al., J. Gen. Microbiol. 130: 2237-2246 (1984)), the nucleic acid molecules of the invention may be utilized in the genetic engineering of this organism to modulate the production of one or more fine chemicals. This modulation may be due to a direct effect of manipulation of a gene of the invention, or it may be due to an indirect effect of such manipulation. For example, by modifying the activity of a protein involved in the biosynthesis or degradation of a fine chemical (i.e., through mutagenesis of the corresponding gene), one may directly modulate the ability of the cell to synthesize or to degrade this compound, thereby modulating the yield and/or efficiency of production of the fine chemical. Similarly, by modulating the activity of a protein which regulates a fine chemical metabolic pathway, one may directly influence whether the production of the desired compound is up- or down-regulated, either of which will modulate the yield or efficiency of production of the fine chemical from the cell.
Indirect modulation of fine chemical production may also result by modifying the activity of a protein of the invention (i.e., by mutagenesis of the corresponding gene) such that the overall ability of the cell to grow and divide or to remain viable and productive is increased. The production of fine chemicals from C. glutamicum is generally accomplished by the large-scale fermentative culture of these microorganisms, conditions which are frequently suboptimal for growth and cell division. By engineering a protein of the invention (e.g., a stress response protein, a cell wall protein, or proteins involved in the metabolism of compounds necessary for cell growth and division to occur, such as nucleotides and amino acids) such that it is better able to survive, grow, and multiply in such conditions, it may be possible to increase the number and productivity of such engineered C. glutamicum cells in large-scale culture, which in turn should result in increased yields and/or efficiency of production of one or more desired fine chemicals. Further, the metabolic pathways of any cell are necessarily interrelated and coregulated. By altering the activity or regulation of any one metabolic pathway in C. glutamicum (i.e., by altering the activity of one of the proteins of the invention which participates in such a pathway), it is possible to concomitantly alter the activity or regulation of other metabolic pathways in this microorganism, which may be directly involved in the synthesis or degradation of a fine chemical. The invention provides novel nucleic acid molecules which encode proteins, referred to herein as MCP proteins, which are capable of, for example, modulating the production or efficiency of production of one or more fine chemicals from C. glutamicum, or of serving as identifying markers for C. glutamicum or related organisms. Nucleic acid molecules encoding an MCP protein are referred to herein as MCP nucleic acid molecules. In a preferred embodiment, the MCP protein is capable of modulating the production or efficiency of production of one or more fine chemicals from C. glutamicum, or of serving as identifying markers for C. glutamicum or related organisms. Examples of such proteins include those encoded by the genes set forth in Table 1.
Accordingly, one aspect of the invention pertains to isolated nucleic acid molecules (e.g., cDNAs, DNAs, or RNAs) comprising a nucleotide sequence encoding an MCP protein or biologically active portions thereof, as well as nucleic acid fragments suitable as primers or hybridization probes for the detection or amplification of MCP-encoding nucleic acid (e.g., DNA or mRNA). In particularly preferred embodiments, the isolated nucleic acid molecule comprises one of the nucleotide sequences set forth in Appendix A or the coding region or a complement thereof of one of these nucleotide sequences. In other particularly preferred embodiments, the isolated nucleic acid molecule of the invention comprises a nucleotide sequence which hybridizes to or is at least about 50%, preferably at least about 60%, more preferably at least about 70%, 80% or 90%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to a nucleotide sequence set forth in Appendix A, or a portion thereof. In other preferred embodiments, the isolated nucleic acid molecule encodes one of the amino acid sequences set forth in Appendix B. The preferred MCP proteins of the present invention also preferably possess at least one of the MCP activities described herein.
In another embodiment, the isolated nucleic acid molecule encodes a protein or portion thereof wherein the protein or portion thereof includes an amino acid sequence which is sufficiently homologous to an amino acid sequence of Appendix B, e.g., sufficiently homologous to an amino acid sequence of Appendix B such that the protein or portion thereof maintains an MCP activity. Preferably, the protein or portion thereof encoded by the nucleic acid molecule maintains the ability to modulate the production or efficiency of production of one or more fine chemicals from C. glutamicum, or of serving as an identifying marker for C. glutamicum or related organisms. In one embodiment, the protein encoded by the nucleic acid molecule is at least about 50%, preferably at least about 60%, and more preferably at least about 70%, 80%, or 90% and most preferably at least about 95%, 96%, 97%, 98%, or 99% or more homologous to an amino acid sequence of Appendix B (e.g., an entire amino acid sequence selected from those sequences set forth in Appendix B). In another preferred embodiment, the protein is a fill length C. glutamicum protein which is substantially homologous to an entire amino acid sequence of Appendix B (encoded by an open reading frame shown in Appendix A).
In another preferred embodiment, the isolated nucleic acid molecule is derived from C. glutamicum and encodes a protein (e.g., an MCP fusion protein) which includes biologically active domain which is at least about 50% or more homologous to one of the amino acid sequences of Appendix B and is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms, and which also includes heterologous nucleic acid sequences encoding a heterologous polypeptide or regulatory regions.
In another embodiment, the isolated nucleic acid molecule is at least 15 nucleotides in length and hybridizes under stringent conditions to a nucleic acid molecule comprising a nucleotide sequence of Appendix A. Preferably, the isolated nucleic acid molecule corresponds to a naturally-occurring nucleic acid molecule. More preferably, the isolated nucleic acid encodes a naturally-occurring C. glutamicum MCP protein, or a biologically active portion thereof.
Another aspect of the invention pertains to vectors, e.g., recombinant expression vectors, containing the nucleic acid molecules of the invention, and host cells into which such vectors have been introduced. In one embodiment, such a host cell is used to produce an MCP protein by culturing the host cell in a suitable medium. The MCP protein can then be isolated from the medium or the host cell.
Yet another aspect of the invention pertains to a genetically altered microorganism in which an MCP gene has been introduced or altered. In one embodiment, the genome of the microorganism has been, altered by introduction of a nucleic acid molecule of the invention encoding wild-type or mutated MCP sequence as a transgene. In another embodiment, an endogenous MCP gene within the genome of the microorganism has been altered, e.g., functionally disrupted, by homologous recombination with an altered MCP gene. In another embodiment, an endogenous or introduced MCP gene in a microorganism has been altered by one or more point mutations, deletions, or inversions, but still encodes a functional MCP protein. In still another embodiment, one or more of the regulatory regions (e.g., a promoter, repressor, or inducer) of an MCP gene in a microorganism has been altered (e.g., by deletion, truncation, inversion, or point mutation) such that the expression of the MCP gene is modulated. In a preferred embodiment, the microorganism belongs to the genus Corynebacterium or Brevibacterium, with Corynebacterium glutamicum being particularly preferred. In a preferred embodiment, the microorganism is also utilized for the production of a desired compound, such as an amino acid, with lysine being particularly preferred.
In another aspect, the invention provides a method of identifying the presence or activity of Cornyebacterium diphtheriae in a subject. This method includes detection of one or more of the nucleic acid or amino acid sequences of the invention (e.g., the sequences set forth in Appendix A or Appendix B) in a subject, thereby detecting the presence or activity of Corynebacterium diphtheriae in the subject.
Still another aspect of the invention pertains to an isolated MCP protein or a portion, e.g., a biologically active portion, thereof. In a preferred embodiment, the isolated MCP protein or portion thereof is capable of modulating the production or efficiency of production of one or more fine chemicals from C glutamicum, or of serving as an identifying marker for C. glutamicum or related organisms. In another preferred embodiment, the isolated MCP protein or portion thereof is sufficiently homologous to an amino acid sequence of Appendix B such that the protein or portion thereof maintains the ability to, for example, modulate the production or efficiency of production of one or more fine chemicals from C. glutamicum, or to serve as identifying markers for C. glutamicum or related organisms.
The invention also provides an isolated preparation of an MCP protein. In preferred embodiments, the MCP protein comprises an amino acid sequence of Appendix B. In another preferred embodiment, the invention pertains to an isolated full length protein which is substantially homologous to an entire amino acid sequence of Appendix B (encoded by an open reading frame set forth in Appendix A). In yet another embodiment, the protein is at least about 50%, preferably at least about 60%, and more preferably at least about 70%, 80%, or 90%, and most preferably at least about 95%, 96%, 97%, 98%, or 99% or more homologous to an entire amino acid sequence of Appendix B. In other embodiments, the isolated MCP protein comprises an amino acid sequence which is at least about 50% or more homologous to one of the amino acid sequences of Appendix B and is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms.
Alternatively, the isolated MCP protein can comprise an amino acid sequence which is encoded by a nucleotide sequence which hybridizes, e.g., hybridizes under stringent conditions, or is at least about 50%, preferably at least about 60%, more preferably at least about 70%, 80%, or 90%, and even more preferably at least about 95%, 96%, 97%, 98,%, or 99% or more homologous, to a nucleotide sequence of Appendix B. It is also preferred that the preferred forms of MCP proteins also have one or more of the MCP bioactivities described herein.
The MCP polypeptide, or a biologically active portion thereof, can be operatively linked to a non-MCP polypeptide to form a fusion protein. In preferred embodiments, this fusion protein has an activity which differs from that of the MCP protein alone. In other preferred embodiments, this fusion protein is capable of modulating the yield, production and/or efficiency of production of one or more fine chemicals from C. glutamicum, or of serving as an identifying marker for C. glutamicum or related organisms. In particularly preferred embodiments, integration of this fusion protein into a host cell modulates production of a desired compound from the cell.
In another aspect, the invention provides methods for screening molecules which modulate the activity of an MCP protein, either by interacting with the protein itself or a substrate or binding partner of the MCP protein, or by modulating the transcription or translation of an MCP nucleic acid molecule of the invention.
Another aspect of the invention pertains to a method for producing a fine chemical. This method involves the culturing of a cell containing a vector directing the expression of an MCP nucleic acid molecule of the invention, such that a fine chemical is produced. In a preferred embodiment, this method further includes the step of obtaining a cell containing such a vector, in which a cell is transfected with a vector directing the expression of an MCP nucleic acid. In another preferred embodiment, this method further includes the step of recovering the fine chemical from the culture. In a particularly preferred embodiment, the cell is from the genus Corynebacterium or Brevibacterium, or is selected from those strains set forth in Table 3.
Another aspect of the invention pertains to methods for modulating production of a molecule from a microorganism. Such methods include contacting the cell with an agent which modulates MCP protein activity or MCP nucleic acid expression such that a cell associated activity is altered relative to this same activity in the absence of the agent. In a preferred embodiment, the cell is modulated for one or more C. glutamicum MCP protein activities, such that the yield, production, and/or efficiency of production of a desired fine chemical by this microorganism is improved. The agent which modulates MCP protein activity can be an agent which stimulates MCP protein activity or MCP nucleic acid expression. Examples of agents which stimulate MCP protein activity or MCP nucleic acid expression include small molecules, active MCP proteins, and nucleic acids encoding MCP proteins that have been introduced into the cell. Examples of agents which inhibit MCP activity or expression include small molecules and antisense MCP nucleic acid molecules.
Another aspect of the invention pertains to methods for modulating yields, production, and/or efficiency of production of a desired compound from a cell, involving the introduction of a wild-type or mutant MCP gene into a cell, either maintained on a separate plasmid or integrated into the genome of the host cell. If integrated into the genome, such integration can be random, or it can take place by homologous recombination such that the native gene is replaced by the introduced copy, causing the production of the desired compound from the cell to be modulated. In a preferred embodiment, said yields are increased. In another preferred embodiment, said chemical is a fine chemical. In a particularly preferred embodiment, said fine chemical is an amino acid. In especially preferred embodiments, said amino acid is L-lysine.
The present invention provides MCP nucleic acid and protein molecules. These MCP nucleic acid molecules may be utilized in the identification of Corynebacterium glutamicum or related organisms, in the mapping of the C. glutamicum genome (or a genome of a closely related organism), or in the identification of microorganisms which may be used to produce fine chemicals, e.g., by fermentation processes. The proteins encoded by these nucleic acids may be utilized in the direct or indirect modulation of the production or efficiency of production of one or more fine chemicals from C. glutamicum, as identifying markers for C. glutamicum or related organisms, in the oxidation of terpenoids or the degradation of hydrocarbons, or as targets for the development of therapeutic pharmaceutical compounds. Aspects of the invention are further explicated below.
I. Fine Chemicals
The term ‘fine chemical’ is art-recognized and includes molecules produced by an organism which have applications in various industries, such as, but not limited to, the pharmaceutical, agriculture, and cosmetics industries. Such compounds include organic acids, such as tartaric acid, itaconic acid, and diaminopimelic acid, both proteinogenic and non-proteinogenic amino acids, purine and pyrimidine bases, nucleosides, and nucleotides (as described e.g. in Kuninaka, A. (1996) Nucleotides and related compounds, p. 561-612, in Biotechnology vol. 6, Rehm et al., eds. VCH: Weinheim, and references contained therein), lipids, both saturated and unsaturated fatty acids (e.g., arachidonic acid), diols (e.g., propane diol, and butane diol), carbohydrates (e.g., hyaluronic acid and trehalose), aromatic compounds (e.g., aromatic amines, vanillin, and indigo), vitamins and cofactors (as described in Ullmann's Encyclopedia of Industrial Chemistry, vol. A27, “Vitamins”, p. 443-613 (1996) VCH: Weinheim and references therein; and Ong, A. S., Niki, E. & Packer, L. (1995) “Nutrition, Lipids, Health, and Disease” Proceedings of the UNESCO/Confederation of Scientific and Technological Associations in Malaysia, and the Society for Free Radical Research Asia, held Sep. 1-3, 1994 at Penang, Malaysia, AOCS Press, (1995)), enzymes, polyketides (Cane et al. (1998) Science 282: 63-68), and all other chemicals described in Gutcho (1983) Chemicals by Fermentation, Noyes Data Corporation, ISBN: 0818805086 and references therein. The metabolism and uses of certain of these fine chemicals are further explicated below.
A. Amino Acid Metabolism and Uses
Amino acids comprise the basic structural units of all proteins, and as such are essential for normal cellular functioning in all organisms. The term “amino acid” is art-recognized. The proteinogenic amino acids, of which there are 20 species, serve as structural units for proteins, in which they are linked by peptide bonds, while the nonproteinogenic amino acids (hundreds of which are known) are not normally found in proteins (see Ulmann's Encyclopedia of Industrial Chemistry, vol. A2, p. 57-97 VCH: Weinheim (1985)). Amino acids may be in the D- or L- optical configuration, though L-amino acids are generally the only type found in naturally-occurring proteins.
Biosynthetic and degradative pathways of each of the 20 proteinogenic amino acids have been well characterized in both prokaryotic and eukaryotic cells (see, for example, Stryer, L. Biochemistry, 3rd edition, pages 578-590 (1988)). The ‘essential’ amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine), so named because they are generally a nutritional requirement due to the complexity of their biosyntheses, are readily converted by simple biosynthetic pathways to the remaining 11 ‘nonessential’ amino acids (alanine, arginine, asparagine, aspartate, cysteine, glutarnate, glutamine, glycine, proline, serine, and tyrosine). Higher animals do retain the ability to synthesize some of these amino acids, but the essential amino acids must be supplied from the diet in order for normal protein synthesis to occur.
Aside from their function in protein biosynthesis, these amino acids are interesting chemicals in their own right, and many have been found to have various applications in the food, feed, chemical, cosmetics, agriculture, and pharmaceutical industries. Lysine is an important amino acid in the nutrition not only of humans, but also of monogastric animals such as poultry and swine. Glutamate is most commonly used as a flavor additive (mono-sodium glutamate, MSG) and is widely used throughout the food industry, as are aspartate, phenylalanine, glycine, and cysteine. Glycine, L-methionine and tryptophan are all utilized in the pharmaceutical industry. Glutamine, valine, leucine, isoleucine, histidine, arginine, proline, serine and alanine are of use in both the pharmaceutical and cosmetics industries. Threonine, tryptophan, and D/L-methionine are common feed additives. (Leuchtenberger, W. (1996) Amino aids—technical production and use, p. 466-502 in Rehm et al. (eds.) Biotechnology vol. 6, chapter 14a, VCH: Weinheim). Additionally, these amino acids have been found to be useful as precursors for the synthesis of synthetic amino acids and proteins, such as N-acetylcysteine, S-carboxymethyl-L-Cysteine, (S)-5-hydroxytryptophan, and others described in Ulmann's Encyclopedia of Industrial Chemistry, vol. A2, p. 57-97, VCH: Weinheim, 1985.
The biosynthesis of these natural amino acids in organisms capable of producing them, such as bacteria, has been well characterized (for review of bacterial amino acid biosynthesis and regulation thereof, see Umbarger, H. E.(1978) Ann. Rev. Biochem. 47: 533-606). Glutamate is synthesized by the reductive amination of α-ketoglutarate, an intermediate in the citric acid cycle. Glutamine, proline, and arginine are each subsequently produced from glutamate. The biosynthesis of serine is a three-step process beginning with 3-phosphoglycerate (an intermediate in glycolysis), and resulting in this amino acid after oxidation, transamination, and hydrolysis steps. Both cysteine and glycine are produced from serine; the former by the condensation of homocysteine with serine, and the latter by the transferal of the side-chain β-carbon atom to tetrahydrofolate, in a reaction catalyzed by serine transhydroxymethylase. Phenylalanine, and tyrosine are synthesized from the glycolytic and pentose phosphate pathway precursors erythrose 4-phosphate and phosphoenolpyruvate in a 9-step biosynthetic pathway that differ only at the final two steps after synthesis of prephenate. Tryptophan is also produced from these two initial molecules, but its synthesis is an 11-step pathway. Tyrosine may also be synthesized from phenylalanine, in a reaction catalyzed by phenylalanine hydroxylase. Alanine, valine, and leucine are all biosynthetic products of pyruvate, the final product of glycolysis. Aspartate is formed from oxaloacetate, an intermediate of the citric acid cycle. Asparagine, methionine, threonine, and lysine are each produced by the conversion of aspartate. Isoleucine is formed from threonine. A complex 9-step pathway results in the production of histidine from 5-phosphoribosyl-1-pyrophosphate, an activated sugar.
Amino acids in excess of the protein synthesis needs of the cell cannot be stored, and are instead degraded to provide intermediates for the major metabolic pathways of the cell (for review see Stryer, L. Biochemistry 3rd ed. Ch. 21 “Amino Acid Degradation and the Urea Cycle” p. 495-516 (1988)). Although the cell is able to convert unwanted amino acids into useful metabolic intermediates, amino acid production is costly in terms of energy, precursor molecules, and the enzymes necessary to synthesize them. Thus it is not surprising that amino acid biosynthesis is regulated by feedback inhibition, in which the presence of a particular amino acid serves to slow or entirely stop its own production (for overview of feedback mechanisms in amino acid biosynthetic pathways, see Stryer, L. Biochemistry, 3rd ed. Ch. 24: “Biosynthesis of Amino Acids and Heme” p. 575-600 (1988)). Thus, the output of any particular amino acid is limited by the amount of that amino acid present in the cell.
B. Vitamin, Cofactor and Nutraceutical Metabolism and Uses
Vitamin, cofactors, and nutraceuticals comprise another group of molecules which the higher animals have lost the ability to synthesize and so must ingest, although they are readily synthesized by other organisms such as bacteria. These molecules are either bioactive substances themselves, or are precursors of biologically active substances which may serve as electron carriers or intermediates in a variety of metabolic pathways. Aside from their nutritive value, these compounds also have significant industrial value as coloring agents, antioxidants, and catalysts or other processing aids. (For an overview of the structure, activity, and industrial applications of these compounds, see, for example, Ullman's Encyclopedia of Industrial Chemistry, “Vitamins” vol. A27, p. 443-613, VCH: Weinheim, 1996.) The term “vitamin” is art-recognized, and includes nutrients which are required by an organism for normal functioning, but which that organism cannot synthesize by itself. The group of vitamins may encompass cofactors and nutraceutical compounds. The language “cofactor” includes nonproteinaceous compounds required for a normal enzymatic activity to occur. Such compounds may be organic or inorganic; the cofactor molecules of the invention are preferably organic. The term “nutraceutical” includes dietary supplements having health benefits in plants and animals, particularly humans. Examples of such molecules are vitamins, antioxidants, and also certain lipids (e.g., polyunsaturated fatty acids).
The biosynthesis of these molecules in organisms capable of producing them, such as bacteria, has been largely characterized (Ullman's Encyclopedia of Industrial Chemistry, “Vitamins” vol. A27, p. 443-613, VCH: Weinheim, 1996; Michal, G. (1999) Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, John Wiley & Sons; Ong, A. S., Niki, E. & Packer, L. (1995) “Nutrition, Lipids, Health, and Disease” Proceedings of the UNESCO/Confederation of Scientific and Technological Associations in Malaysia, and the Society for Free Radical Research—Asia, held Sep. 1-3, 1994 at Penang, Malaysia, AOCS Press: Champaign, Ill. X, 374 S).
Thiamin (vitamin B1) is produced by the chemical coupling of pyrimidine and thiazole moieties. Riboflavin (vitamin B2) is synthesized from guanosine-5′-triphosphate (GTP) and ribose-5′-phosphate. Riboflavin, in turn, is utilized for the synthesis of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). The family of compounds collectively termed ‘vitamin B6’ (e.g., pyridoxine, pyridoxamine, pyridoxa-5′-phosphate, and the commercially used pyridoxin hydrochloride) are all derivatives of the common structural unit, 5-hydroxy-6-methylpyridine. Pantothenate (pantothenic acid, (R)-(+)—N-(2,4-dihydroxy-3,3-dimethyl-β-oxobutyl)-α-alanine) can be produced either by chemical synthesis or by fermentation. The final steps in pantothenate biosynthesis consist of the ATP-driven condensation of β-alanine and pantoic acid. The enzymes responsible for the biosynthesis steps for the conversion to pantoic acid, to β-alanine and for the condensation to panthotenic acid are known. The metabolically active form of pantothenate is Coenzyme A, for which the biosynthesis proceeds in 5 enzymatic steps. Pantothenate, pyridoxal-5′-phosphate, cysteine and ATP are the precursors of Coenzyme A. These enzymes not only catalyze the formation of panthothante, but also the production of (R)-pantoic acid, (R)-pantolacton, (R)-panthenol (provitamin B5), pantetheine (and its derivatives) and coenzyme A.
Biotin biosynthesis from the precursor molecule pimeloyl-CoA in microorganisms has been studied in detail and several of the genes involved have been identified. Many of the corresponding proteins have been found to also be involved in Fe-cluster synthesis and are members of the nifS class of proteins. Lipoic acid is derived from octanoic acid, and serves as a coenzyme in energy metabolism, where it becomes part of the pyruvate dehydrogenase complex and the α-ketoglutarate dehydrogenase complex. The folates are a group of substances which are all derivatives of folic acid, which is turn is derived from L-glutamic acid, p-amino-benzoic acid and 6-methylpterin. The biosynthesis of folic acid and its derivatives, starting from the metabolism intermediates guanosine-5′-triphosphate (GTP), L-glutamic acid and p-amino-benzoic acid has been studied in detail in certain microorganisms.
Corrinoids (such as the cobalamines and particularly vitamin B12) and porphyrines belong to a group of chemicals characterized by a tetrapyrole ring system The biosynthesis of vitamin B12 is sufficiently complex that it has not yet been completely characterized, but many of the enzymes and substrates involved are now known. Nicotinic acid (nicotinate), and nicotinamide are pyridine derivatives which are also termed ‘niacin’. Niacin is the precursor of the important coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate) and their reduced forms.
The large-scale production of these compounds has largely relied on cell-free chemical syntheses, though some of these chemicals have also been produced by large-scale culture of microorganisms, such as riboflavin, Vitamin B6, pantothenate, and biotin. Only Vitamin B2 is produced solely by fermentation, due to the complexity of its synthesis. In vitro methodologies require significant inputs of materials and time, often at great cost.
C. Purine, Pyrimidine, Nucleoside and Nucleotide Metabolism and Uses
Purine and pyrimidine metabolism genes and their corresponding proteins are important targets for the therapy of tumor diseases and viral infections. The language “purine” or “pyrimidine” includes the nitrogenous bases which are constituents of nucleic acids, co-enzymes, and nucleotides. The term “nucleotide” includes the basic structural units of nucleic acid molecules, which are comprised of a nitrogenous base, a pentose sugar (in the case of RNA, the sugar is ribose; in the case of DNA, the sugar is D-deoxyribose), and phosphoric acid. The language “nucleoside” includes molecules which serve as precursors to nucleotides, but which are lacking the phosphoric acid moiety that nucleotides possess. By inhibiting the biosynthesis of these molecules, or their mobilization to form nucleic acid molecules, it is possible to inhibit RNA and DNA synthesis; by inhibiting this activity in a fashion targeted to cancerous cells, the ability of tumor cells to divide and replicate may be inhibited. Additionally, there are nucleotides which may serve as energy stores (e.g., ADP, ATP) or as coenzymes (i.e., FAD and NAD).
Several publications have described the use of these chemicals for these medical indications, by influencing purine and/or pyrimidine metabolism (e.g. Christopherson, R. I. and Lyons, S. D. (1990) “Potent inhibitors of de novo pyrimidine and purine biosynthesis as chemotherapeutic agents.” Med. Res. Reviews 10: 505-548). Studies of enzymes involved in purine and pyrimidine metabolism have been focused on the development of new drugs which can be used, for example, as immunosuppressants or anti-proliferants (Smith, J. L., (1995) “Enzymes in nucleotide synthesis.” Curr. Opin. Struct. Biol. 5: 752-757; (1995) Biochem Soc. Transact. 23: 877-902). However, purine and pyrimidine bases, nucleosides and nucleotides have other utilities: as intermediates in the biosynthesis of several fine chemicals (e.g., thiamine, S-adenosyl-methionine, folates, or riboflavin), as energy carriers for the cell (e.g., ATP or GTP), and for chemicals themselves, commonly used as flavor enhancers (e.g., IMP or GMP) or for several medicinal applications (see, for example, Kuninaka, A. (1996) Nucleotides and Related Compounds in Biotechnology vol. 6, Rehm et al., eds. VCH: Weinheim, p. 561-612). Also, enzymes involved in purine, pyrimidine, nucleoside, or nucleotide metabolism are increasingly serving as targets against which chemicals for crop protection, including fungicides, herbicides and insecticides, are developed.
The metabolism of these compounds in bacteria has been characterized (for reviews see, for example, Zalkin, H. and Dixon, J. E. (1992) “de novo purine nucleotide biosynthesis”, in: Progress in Nucleic Acid Research and Molecular Biology, vol. 42, Academic Press:, p. 259-287; and Michal, G. (1999) “Nucleotides and Nucleosides”, Chapter 8 in: Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, Wiley: New York). Purine metabolism has been the subject of intensive research, and is essential to the normal functioning of the cell. Impaired purine metabolism in higher animals can cause severe disease, such as gout. Purine nucleotides are synthesized from ribose-5-phosphate, in a series of steps through the intermediate compound inosine-5′-phosphate (IMP), resulting in the production of guanosine-5′-monophosphate (GMP) or adenosine-5′-monophosphate (AMP), from which the triphosphate forms utilized as nucleotides are readily formed. These compounds are also utilized as energy stores, so their degradation provides energy for many different biochemical processes in the cell. Pyrimidine biosynthesis proceeds by the format ion of uridine-5′-monophosphate (UMP) from ribose-5-phosphate. UMP, in turn, is converted to cytidine-5′-triphosphate (CTP). The deoxy- forms of all of these nucleotides are produced in a one step reduction reaction from the diphosphate ribose form of the nucleotide to the diphosphate deoxyribose form of the nucleotide. Upon phosphorylation, these molecules are able to participate in DNA synthesis.
D. Trehalose Metabolism and Uses
Trehalose consists of two glucose molecules, bound in α, α-1,1 linkage. It is commonly used in the food industry as a sweetener, an additive for dried or frozen foods, and in beverages. However, it also has applications in the pharmaceutical, cosmetics and biotechnology industries (see, for example, Nishimoto et al., (1998) U.S. Pat. No. 5,759,610; Singer, M. A. and Lindquist, S. (998) Trends Biotech. 16: 460-467; Paiva, C. L. A. and Panek, A. D. (1996) Biotech. Ann. Rev. 2: 293-314; and Shiosaka, M. (1997) J. Japan 172: 97-102). Trehalose is produced by enzymes from many microorganisms and is naturally released into the surrounding medium, from which it can be collected us ing met hods known in the art.
II. Elements and Methods of the Invention
The present invention is based, at least in part, on the discovery of novel molecules, referred to herein as MCP nucleic acid molecules. These MCP nucleic acid molecules are useful not only for the identification of C. glutamicum or related bacterial species, but also as markers for the mapping of the C. glutamicum genome and in the identification of bacteria useful for the production of fine chemicals by, e.g., fermentative processes. The present invention is also based, at least in part, on the MCP protein molecules encoded by these MCP nucleic acid molecules. These MCP proteins are capable of modulating the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, of serving as identifying markers for C. glutamicum or related organisms, of degrading hydrocarbons, and of serving as targets for the development of therapeutic pharmaceutical compounds. In one embodiment, the MCP molecules of the invention directly or indirectly participate in one or more fine chemical metabolic pathways in C. glutamicum. In a preferred embodiment, the activity the MCP molecules of the invention to indirectly or directly participate in such metabolic pathways has an impact on the production of a desired fine chemical by this microorganism. In a particularly preferred embodiment, the MCP molecules of the invention are modulated in activity, such that the C. glutamicum metabolic pathways in which the MCP proteins of the invention participate are modulated in efficiency or output, which either directly or indirectly modulates the production or efficiency of production of a desired fine chemical by C. glutamicum.
The language, “MCP protein” or “MCP polypeptide” includes proteins which are able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target protein for drug screening or design, or to serve as identifying markers for C. glutamicum or related organisms. Examples of MCP proteins include those encoded by the MCP genes set forth in Table 1 and Appendix A. The terms “MCP gene” or “MCP nucleic acid sequence” include nucleic acid sequences encoding an MCP protein, which consist of a coding region and also corresponding untranslated 5′ and 3′ sequence regions. Examples of MCP genes include those set forth in Table 1. The terms “production” or “productivity” are art-recognized and include the concentration of the fermentation product (for example, the desired fine chemical) formed within a given time and a given fermentation volume (e.g., kg product per hour per liter). The term “efficiency of production” includes the time required for a particular level of production to be achieved (for example, how long it takes for the cell to attain a particular rate of output of a fine chemical). The term “yield” or “product/carbon yield” is art-recognized and includes the efficiency of the conversion of the carbon source into the product (ie., fine chemical). This is generally written as, for example, kg product per kg carbon source. By increasing the yield or production of the compound, the quantity of recovered molecules, or of useful recovered molecules of that compound in a given amount of culture over a given amount of time is increased. The terms “biosynthesis” or a “biosynthetic pathway” are art-recognized and include the synthesis of a compound, preferably an organic compound, by a cell from intermediate compounds in what may be a multistep and highly regulated process. The terms “degradation” or a “degradation pathway” are art-recognized and include the breakdown of a compound, preferably an organic compound, by a cell to degradation products (generally speaking, smaller or less complex molecules) in what may be a multistep and highly regulated process. The language “metabolism” is art-recognized and includes the totality of the biochemical reactions that take place in an organism. The metabolism of a particular compound, then, (e.g., the metabolism of an amino acid such as glycine) comprises the overall biosynthetic, modification, and degradation pathways in the cell related to this compound.
In another embodiment, the MCP molecules of the invention are capable of modulating the production of a desired molecule, such as a fine chemical, in a microorganism such as C. glutamicum, either directly or indirectly. Using recombinant genetic techniques, one or more of the MCP proteins of the invention may be manipulated such that its function is modulated. Such modulation of function may result in the modulation of the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum.
For example, by modifying the activity of a protein involved in the biosynthesis or degradation of a fine chemical (i.e., through mutagenesis of the corresponding gene), one may directly modulate the ability of the cell to synthesize or to degrade this compound, thereby modulating the yield and/or efficiency of production of the fine chemical. Similarly, by modulating the activity of a protein which regulates a fine chemical metabolic pathway, one may directly influence whether the production of the desired compound is up- or down-regulated, either of which will modulate the yield or efficiency of production of the fine chemical from the cell.
Indirect modulation of fine chemical production may also result by modifying the activity of a protein of the invention (i.e., by mutagenesis of the corresponding gene) such that the overall ability of the cell to grow and divide or to remain viable and productive is increased. The production of fine chemicals from C. glutamicum is generally accomplished by the large-scale fermentative culture of these microorganisms, conditions which are frequently suboptimal for growth and cell division. By engineering a protein of the invention (e.g., a stress response protein, a cell wall protein, or proteins involved in the metabolism of compounds necessary for cell growth and division to occur, such as nucleotides and amino acids) such that it is better able to survive, grow, and multiply in such conditions, it may be possible to increase the number and productivity of such engineered C. glutamicum cells in large-scale culture, which in turn should result in increased yields and/or efficiency of production of one or more desired fine chemicals. Further, the metabolic pathways of any cell are necessarily interrelated and coregulated. By altering the activity or regulation of any one metabolic pathway in C. glutamicum (i.e., by altering the activity of one of the proteins of the invention which participates in such a pathway), it is possible to concomitantly alter the activity or regulation of other metabolic pathways in this microorganism, which may be directly involved in the synthesis or degradation of a fine chemical.
The isolated nucleic acid sequences of the invention are contained within the genome of a Corynebacterium glutamicum strain available through the American Type Culture Collection, given designation ATCC 13032. The nucleotide sequences of the isolated C. glutamicum MCP nucleic acid molecules and the predicted amino acid sequences of the C. glutamicum MCP proteins are shown in Appendices A and B, respectively. Computational analyses were performed which classified and/or identified many of these nucleotide sequences as sequences having homology to E. coli or Bacillus subtilis genes.
The present invention also pertains to proteins which have an amino acid sequence which is substantially homologous to an amino acid sequence of Appendix B.
As used herein, a protein which has an amino acid sequence which is substantially homologous to a selected amino acid sequence is least about 50% homologous to the selected amino acid sequence, e.g., the entire selected amino acid sequence. A protein which has an amino acid sequence which is substantially homologous to a selected amino acid sequence can also be least about 50-60%, preferably at least about 60-70%, and more preferably at least about 70-80%, 80-90%, or 90-95%, and most preferably at least about 96%, 97%, 98%, 99% or more homologous to the selected amino acid sequence.
The MCP protein or a biologically active portion or fragment thereof of the invention is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms.
Various aspects of the invention are described in further detail in the following subsections:
A. Isolated Nucleic Acid Molecules
One aspect of the invention pertains to isolated nucleic acid molecules that encode MCP polypeptides or biologically active portions thereof, as well as nucleic acid fragments sufficient for use as hybridization probes or primers for the identification or amplification of MCP-encoding nucleic acid (e.g., MCP DNA). These nucleic acid molecules may be used to identify C. glutamicum or related organisms, to map the genome of C. glutamicum or closely related bacteria, or to identify microorganisms useful for the production of fine chemicals, e.g., by fermentative processes. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA) and RNA molecules (e.g., mRNA) and analogs of the DNA or RNA generated using nucleotide analogs. This term also encompasses untranslated sequence located at both the 3′ and 5′ ends of the coding region of the gene: at least about 100 nucleotides of sequence upstream from the 5′ end of the coding region and at least about 20 nucleotides of sequence downstream from the 3′ end of the coding region of the gene. The nucleic acid molecule can be single-stranded or double-stranded, but preferably is double-stranded DNA. An “isolated” nucleic acid molecule is one which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (ie., sequences located at the 5′ and 3′ ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated MCP nucleic acid molecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell from which the nucleic acid is derived (e.g, a C. glutamicum cell). Moreover, an “isolated” nucleic acid molecule, such as a DNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized.
A nucleic acid molecule of the present invention, e.g., a nucleic acid molecule having a nucleotide sequence of Appendix A, or a portion thereof, can be isolated using standard molecular biology techniques and the sequence information provided herein. For example, a C. glutamicum MCP DNA can be isolated from a C. glutamicum library using all or portion of one of the sequences of Appendix A as a hybridization probe and standard hybridization techniques (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd ed, Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989). Moreover, a nucleic acid molecule encompassing all or a portion of one of the sequences of Appendix A can be isolated by the polymerase chain reaction using oligonucleotide primers designed based upon this sequence (e.g., a nucleic acid molecule encompassing all or a portion of one of the sequences of Appendix A can be isolated by the polymerase chain reaction using oligonucleotide primers designed based upon this same sequence of Appendix A). For example, mRNA can be isolated from normal endothelial cells (e.g., by the guanidinium-thiocyanate extraction procedure of Chirgwin et al. (1979) Biochemistry 18: 5294-5299) and DNA can be prepared using reverse transcriptase (e.g., Moloney MLV reverse transcriptase, available from Gibco/BRL, Bethesda, Md., or AMV reverse transcriptase, available from Seikagaku America, Inc., St. Petersburg, Fla.) and random polynucleotide primers or oligonucleotide primers based upon one of the nucleotide sequences shown in Appendix A. Synthetic oligonucleotide primers for polymerase chain reaction amplification can be designed based upon one of the nucleotide sequences shown in Appendix A. A nucleic acid of the invention can be amplified using cDNA or, alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to an MCP nucleotide sequence can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.
In a preferred embodiment, an isolated nucleic acid molecule of the invention comprises one of the nucleotide sequences shown in Appendix A. The sequences of Appendix A correspond to the Corynebacterium glutamicum MCP DNAs of the invention. This cDNA comprises sequences encoding MCP proteins (i.e., the “coding region”, indicated in each sequence in Appendix A), as well as 5′ untranslated sequences and 3′ untranslated sequences, also indicated in Appendix A. Alternatively, the nucleic acid molecule can comprise only the coding region of any of the sequences in Appendix A.
For the purposes of this application, it will be understood that each of the sequences set forth in Appendix A has an identifying RXA or RXN number having the designation “RXA” or “RXN” followed by 5 digits (ie., RXA00003 or RXN00022). Each of these sequences comprises up to three parts: a 5′ upstream region, a coding region, and a downstream region. Each of these three regions is identified by the same RXA or RXN designation to eliminate confusion. The recitation “one of the sequences in Appendix A”, then, refers to any of the sequences in Appendix A, which may be distinguished by their differing RXA or RXN designations. The coding region of each of these sequences is translated into a corresponding amino acid sequence, which is set forth in Appendix B. The sequences of Appendix B are identified by the same RXA or RXN designations as Appendix A, such that they can be readily correlated. For example, the amino acid sequence in Appendix B designated RXA00003 is a translation of the coding region of the nucleotide sequence of nucleic acid molecule RXA00003 in Appendix A, and the amino acid sequence in Appendix B designated RXN00022 is a translation of the coding region of the nucleotide sequence of nucleic acid molecule RXN00022 in Appendix A. Each of the RXA and RXN nucleotide and amino acid sequences of the invention has also been assigned a SEQ ID NO, as indicated in Table 1.
Several of the genes of the invention are “F-designated genes”. An F-designated gene includes those genes set forth in Table 1 which have an ‘F’ in front of the RXA designation. For example, SEQ ID NO:3, designated, as indicated on Table 1, as “F RXA01638”, is an F-designated gene, as are SEQ ID NOs: 5, 9, and 11 (designated on Table 1 as “F RXA01639”, “F RXA01590”, and “F RXA01542”, respectively).
In one embodiment, the nucleic acid molecules of the present invention are not intended to include those compiled in Table 2.
In another preferred embodiment an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule which is a complement of one of the nucleotide sequences shown in Appendix A, or a portion thereof. A nucleic acid molecule which is complementary to one of the nucleotide sequences shown in Appendix A is one which is sufficiently complementary to one of the nucleotide sequences shown in Appendix A such that it can hybridize to one of the nucleotide sequences shown in Appendix A, thereby forming a stable duplex.
In still another preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleotide sequence which is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to a nucleotide sequence shown in Appendix A, or a portion thereof. Ranges and identity values intermediate to the above-recited ranges, (e.g., 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included. In an additional preferred embodiment, an isolated nucleic acid molecule of the invention comprises a nucleotide sequence which hybridizes, e.g., hybridizes under stringent conditions, to one of the nucleotide sequences shown in Appendix A, or a portion thereof.
Moreover, the nucleic acid molecule of the invention can comprise only a portion of the coding region of one of the sequences in Appendix A, for example a fragment which can be used as a probe or primer or a fragment encoding a biologically active portion of an MCP protein. The nucleotide sequences determined from the cloning of the MCP genes from C. glutamicum allows for the generation of probes and primers designed for use in identifying and/or cloning MCP homologues in other cell types and organisms, as well as MCP homologues from other Corynebacteria or related species. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, preferably about 25, more preferably about 40, 50 or 75 consecutive nucleotides of a sense strand of one of the sequences set forth in Appendix A, an anti-sense sequence of one of the sequences set forth in Appendix A, or naturally occurring mutants thereof. Primers based on a nucleotide sequence of Appendix A can be used in PCR reactions to clone MCP homologues. Probes based on the MCP nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In preferred embodiments, the probe further comprises a label group attached thereto, e.g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme cofactor. Such probes can be used as a part of a diagnostic test kit for identifying cells which misexpress an MCP protein, such as by measuring a level of an MCP-encoding nucleic acid in a sample of cells, e.g., detecting MCP mRNA levels or determining whether a genomic MCP gene has been mutated or deleted.
In one embodiment, the nucleic acid molecule of the invention encodes a protein or portion thereof which includes an amino acid sequence which is sufficiently homologous to an amino acid sequence of Appendix B such that the protein or portion thereof maintains the ability to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms. As used herein, the language “sufficiently homologous” refers to proteins or portions thereof which have amino acid sequences which include a minimum number of identical or equivalent (e.g., an amino acid residue which has a similar side chain as an amino acid residue in one of the sequences of Appendix B) amino acid residues to an amino acid sequence of Appendix B such that the protein or portion thereof is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms. Examples of such activities are also described herein. Thus, “the function of an MCP protein” contributes to the overall regulation of one or more fine chemical metabolic pathways, or to the degradation of a hydrocarbon, or to the oxidation of a terpenoid.
In another embodiment, the protein is at least about 50-60%, preferably at least about 60-70%, and more preferably at least about 70-80%, 80-90%, 90-95%, and most preferably at least about 96%, 97%, 98%, 99% or more homologous to an entire amino acid sequence of Appendix B.
Portions of proteins encoded by the MCP nucleic acid molecules of the invention are preferably biologically active portions of one of the MCP proteins. As used herein, the term “biologically active portion of an MCP protein” is intended to include a portion, e.g., a domain/motif, of an MCP protein that modulates the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, that degrades hydrocarbons, that oxidizes terpenoids, that may serve as a target for drug development, or that may serve as an identifying marker for C. glutamicum or related organisms. To determine whether an MCP protein or a biologically active portion thereof can modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, can degrade hydrocarbons, or can oxidize terpenoids, an assay of activity may be performed. Such assay methods are well known to those of ordinary skill in the art, as detailed in Example 8 of the Exemplification.
Additional nucleic acid fragments encoding biologically active portions of an MCP protein can be prepared by isolating a portion of one of the sequences in Appendix B, expressing the encoded portion of the MCP protein or peptide (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of the MCP protein or peptide.
The invention further encompasses nucleic acid molecules that differ from one of the nucleotide sequences shown in Appendix A (and portions thereof) due to degeneracy of the genetic code and thus encode the same MCP protein as that encoded by the nucleotide sequences shown in Appendix A. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in Appendix B. In a still further embodiment, the nucleic acid molecule of the invention encodes a full length C. glutamicum protein which is substantially homologous to an amino acid sequence of Appendix B (encoded by an open reading frame shown in Appendix A).
It will be understood by one of ordinary skill in the art that in one embodiment the sequences of the invention are not meant to include the sequences of the prior art, such as those Genbank sequences set forth in Tables 2 or 4 which were available prior to the present invention. In one embodiment, the invention includes nucleotide and amino acid sequences having a percent identity to a nucleotide or amino acid sequence of the invention which is greater than that of a sequence of the prior art (e.g., a Genbank sequence (or the protein encoded by such a sequence) set forth in Tables 2 or 4). For example, the invention includes a nucleotide sequence which is greater than and/or at least 39% identical to the nucleotide sequence designated RXA00008 (SEQ ID NO: 1549), a nucleotide sequence which is greater than and/or at least 42% identical to the nucleotide sequence designated RXA00059 (SEQ ID NO: 1571), and a nucleotide sequence which is greater than and/or at least 39% identical to the nucleotide sequence designated RXA00096 (SEQ ID NO:93). One of ordinary skill in the art would be able to calculate the lower threshold of percent identity for any given sequence of the invention by examining the GAP-calculated percent identity scores set forth in Table 4 for each of the three top hits for the given sequence, and by subtracting the highest GAP-calculated percent identity from 100 percent. One of ordinary skill in the art will also appreciate that nucleic acid and amino acid sequences having percent identities greater than the lower threshold so calculated (e.g., at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more identical) are also encompassed by the invention.
In addition to the C. glutamicum MCP nucleotide sequences shown in Appendix A, it will be appreciated by those of ordinary skill in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of MCP proteins may exist within a population (e.g., the C. glutamicum population). Such genetic polymorphism in the MCP gene may exist among individuals within a population due to natural variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame encoding an MCP protein, preferably a C. glutamicum MCP protein. Such natural variations can typically result in 1-5% variance in the nucleotide sequence of the MCP gene. Any and all such nucleotide variations and resulting amino acid polymorphisms in MCP that are the result of natural variation and that do not alter the functional activity of MCP proteins are intended to be within the scope of the invention.
Nucleic acid molecules corresponding to natural variants and non-C. glutamicum homologues of the C. glutamicum MCP DNA of the invention can be isolated based on their homology to the C. glutamicum MCP nucleic acid disclosed herein using the C. glutamicum DNA, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions. Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 15 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising a nucleotide sequence of Appendix A. In other embodiments, the nucleic acid is at least 30, 50, 100, 250 or more nucleotides in length. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other. Preferably, the conditions are such that sequences at least about 65%, more preferably at least about 70%, and even more preferably at least about 75% or more homologous to each other typically remain hybridized to each other. Such stringent conditions are known to those of ordinary skill in the art and can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. A preferred, non-limiting example of stringent hybridization conditions are hybridization in 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 50-65° C.
Preferably, an isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to a sequence of Appendix A corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein). In one embodiment, the nucleic acid encodes a natural C. glutamicum MCP protein.
In addition to naturally-occurring variants of the MCP sequence that may exist in the population, one of ordinary skill in the art will further appreciate that changes can be introduced by mutation into a nucleotide sequence of Appendix A, thereby leading to changes in the amino acid sequence of the encoded MCP protein, without altering the functional ability of the MCP protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in a sequence of Appendix A. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequence of one of the MCP proteins (Appendix B) without altering the activity of said MCP protein, whereas an “essential” amino acid residue is required for MCP protein activity. Other amino acid residues, however, (e.g., those that are not conserved or only semi-conserved in the domain having MCP activity) may not be essential for activity and thus are likely to be amenable to alteration without altering MCP activity.
Accordingly, another aspect of the invention pertains to nucleic acid molecules encoding MCP proteins that contain changes in amino acid residues that are not essential for MCP activity. Such MCP proteins differ in amino acid sequence from a sequence contained in Appendix B yet retain at least one of the MCP activities described herein. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 50% homologous to an amino acid sequence of Appendix B and is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms. Preferably, the protein encoded by the nucleic acid molecule is at least about 50-60% homologous to one of the sequences in Appendix B, more preferably at least about 60-70% homologous to one of the sequences in Appendix B, even more preferably at least about 70-80%, 80-90%, 90-95% homologous to one of the sequences in Appendix B, and most preferably at least about 96%, 97%, 98%, or 99% homologous to one of the sequences in Appendix B.
To determine the percent homology of two amino acid sequences (e.g., one of the sequences of Appendix B and a mutant form thereof) or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of one protein or nucleic acid for optimal alignment with the other protein or nucleic acid). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in one sequence (e.g., one of the sequences of Appendix B) is occupied by the same amino acid residue or nucleotide as the corresponding position in the other sequence (e.g. a mutant form of the sequence selected from Appendix B), then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid “homology” is equivalent to amino acid or nucleic acid “identity”). The percent homology between the two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology=# of identical positions/total # of positions×100).
An isolated nucleic acid molecule encoding an MCP protein homologous to a protein sequence of Appendix B can be created by introducing one or more nucleotide substitutions, additions or deletions into a nucleotide sequence of Appendix A such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein. Mutations can be introduced into one of the sequences of Appendix A by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in an MCP protein is preferably replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of an MCP coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for an MCP activity described herein to identify mutants that retain MCP activity. Following mutagenesis of one of the sequences of Appendix A, the encoded protein can be expressed recombinantly and the activity of the protein can be determined using, for example, assays described herein (see Example 8 of the Exemplification).
In addition to the nucleic acid molecules encoding MCP proteins described above, another aspect of the invention pertains to isolated nucleic acid molecules which are antisense thereto. An “antisense” nucleic acid comprises a nucleotide sequence which is complementary to a “sense” nucleic acid encoding a protein, e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence. Accordingly, an antisense nucleic acid can hydrogen bond to a sense nucleic acid. The antisense nucleic acid can be complementary to an entire MCP coding sand, or to only a portion thereof. In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding an MCP protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues (e.g., the entire coding region of SEQ ID NO. 1 (RXN01638) comprises nucleotides 1 to 900°). In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding MCP. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).
Given the coding strand sequences encoding MCP disclosed herein (e.g., the sequences set forth in Appendix A), antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of MCP mRNA, but more preferably is an oligonucleotide which is antisense to only a portion of the coding or noncoding region of MCP mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of MCP mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed by chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used. Examples of modified nucleotides which can be used to generate the antisense nucleic acid include 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, S-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6 isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).
The antisense nucleic acid molecules of the invention are typically administered to a cell or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding an MCP protein to thereby inhibit expression of the protein, e.g., by inhibiting transcription and/or translation. The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule which binds to DNA duplexes, through specific interactions in the major groove of the double helix. The antisense molecule can be modified such that it specifically binds to a receptor or an antigen expressed on a selected cell surface, e.g., by linking the antisense nucleic acid molecule to a peptide or an antibody which binds to a cell surface receptor or antigen. The antisense nucleic acid molecule can also be delivered to cells using the vectors described herein. To achieve sufficient intracellular concentrations of the antisense molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong prokaryotic, viral, or eukaryotic promoter are preferred.
In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gaultier et al. (1987) Nucleic Acids. Res. 15:6625-6641). The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (Inoue et al. (1987) Nucleic Acids Res. 15:6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. (1987) FEBS Lett. 215:327-330).
In still another embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity which are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes (described in Haselhoff and Gerlach (1988) Nature 334:585-591)) can be used to catalytically cleave MCP mRNA transcripts to thereby inhibit translation of MCP mRNA. A ribozyme having specificity for an MCP-encoding nucleic acid can be designed based upon the nucleotide sequence of an MCP DNA disclosed herein (i.e., SEQ ID NO. 1 (RXN01368) in Appendix A). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in an MCP-encoding mRNA. See, e.g., Cech et al. U.S. Pat. No. 4,987,071 and Cech et al U.S. Pat. No. 5,116,742. Alternatively, MCP mRNA can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel, D. and Szostak, J. W. (1993) Science 261:1411-1418.
Alternatively, MCP gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of an MCP nucleotide sequence (e.g., an MCP promoter and/or enhancers) to form triple helical structures that prevent transcription of an MCP gene in target cells. See generally, Helene, C. (1991) Anticancer Drug Des. 6(6):569-84; Helene, C. et al. (1992) Ann. N.Y. Acad. Sci. 660:2736; and Maher, L. J. (1992) Bioassays 14(12):807-15.
B. Recombinant Expression Vectors and Host Cells
Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding an MCP protein (or a portion thereof). As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.
The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, which is operatively linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner which allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). The term “regulatory sequence” is intended to include promoters, repressor binding sites, activator binding sites, enhancer regions and other expression control elements (e.g., terminators, other elements of mRNA secondary structure, or polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel; Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many types of host cell and those which direct expression of the nucleotide sequence only in certain host cells. Preferred regulatory sequences are, for example, promoters such as cos-, tac-, trp-, tet-, trp-tet-, lpp-, lac-, lpp-lac-, lacIq-, T7-, T5-, T3-, gal-, trc-, ara-, SP6-, arny, SPO2, λ- PR- or λPL, which are used preferably in bacteria. Additional regulatory sequences are, for example, promoters from yeasts and fungi, such as ADC1, MFα, AC, P-60, CYC1, GAPDH, TEF, rp28, ADH, promoters from plants such as CaMV/35S, SSU, OCS, lib4, usp, STLS1, B33, nos or ubiquitin- or phaseolin-promoters. It is also possible to use artificial promoters. It will be appreciated by those of ordinary skill in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., MCP proteins, mutant forms of MCP proteins, fusion proteins, etc.).
The recombinant expression vectors of the invention can be designed for expression of MCP proteins in prokaryotic or eukaryotic cells. For example, MCP genes can be expressed in bacterial cells such as C glutamicum, insect cells (using baculovirus expression vectors), yeast and other fungal cells (see Romanos, M. A. et al. (1992) “Foreign gene expression in yeast: a review”, Yeast 8: 423-488; van den Hondel, C. A. M. J. J. et al. (1991) “Heterologous gene expression in filamentous fungi” in: More Gene Manipulations in Fungi, J. W. Bennet & L. L. Lasure, eds., p. 396-428: Academic Press: San Diego; and van den Hondel, C. A. M. J. J. & Punt, P. J. (1991) “Gene transfer systems and vector development for filamentous fungi, in: Applied Molecular Genetics of Fungi, Peberdy, J. F. et al., eds., p. 1-28, Cambridge University Press: Cambridge), algae and multicellular plant cells (see Schmidt, R. and Willmitzer, L. (1988) High efficiency Agrobacterium tumefactiens—mediated transformation of Arabidopsis thaliana leaf and cotyledon explants” Plant Cell Rep.: 583-586), or mammalian cells. Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.
Expression of proteins in prokaryotes is most often carried out with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: 1) to increase expression of recombinant protein; 2) to increase the solubility of the recombinant protein; and 3) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase.
Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D. B. and Johnson, K. S. (1988) Gene 67:31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. In one embodiment, the coding sequence of the MCP protein is cloned into a pGEX expression vector to create a vector encoding a fusion protein comprising, from the N-terminus to the C-terminus, GST-thrombin cleavage site-X protein. The fusion protein can be purified by affinity chromatography using glutathione-agarose resin. Recombinant MCP protein unfused to GST can be recovered by cleavage of the fusion protein with thrombin.
Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amann et al., (1988) Gene 69:301-315), pLG338, pACYC184, pBR322, pUC18, pUC19, pKC30, pRep4, pHS1, pHS2, pPLc236, pMBL24, pLG200, pUR290, pIN-III113-B1, λgt11, pBdCl, and pET 11d (Studier et al., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 60-89; and Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: N.Y. IBSN 0 444 904018). Target gene expression from the pTrc vector relies on host RNA polymerase transcription from a hybrid trp-lac fusion promoter. Target gene expression from the pET 11d vector relies on transcription from a T7 gn10-lac fusion promoter mediated by a coexpressed viral RNA polymerase (T7 gn1). This viral polymerase is supplied by host strains BL21(DE3) or HMS174(DE3) from a resident λ prophage harboring a T7 gn1 gene under the transcriptional control of the lacUV 5 promoter. For transformation of other varieties of bacteria, appropriate vectors may be selected. For example, the plasmids pIJ101, pIJ364, pIJ702 and pIJ361 are known to be useful in transforming Streptomyces, while plasmids pUB110, pC194, or pBD214 are suited for transformation of Bacillus species. Several plasmids of use in the transfer of genetic information into Corynebacterium include pHM 1519, pBL1, pSA77, or pAJ667 (Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: N.Y. IBSN 0 444 904018).
One strategy to maximize recombinant protein expression is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein (Gottesman, S., Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128). Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in the bacterium chosen for expression, such as C. glutamicum (Wada et al. (1992) Nucleic Acids Res. 20:2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.
In another embodiment, the MCP protein expression vector is a yeast expression vector. Examples of vectors for expression in yeast S. cerevisiae include pYepSec1 (Baldari, et al., (1987) Embo J 6:229-234), 2μ, pAG-1, Yep6, Yep13, pEMBLYe23, pMFa (Kurjan and Herskowitz, (1982) Cell 30:933-943), pJRY88 (Schultz et al., (1987) Gene 54:113-123), and pYES2 (Invitrogen Corporation, San Diego, Calif.). Vectors and methods for the construction of vectors appropriate for use in other fungi, such as the filamentous fungi, include those detailed in: van den Hondel, C. A. M. J. J. & Punt, P. J. (1991) “Gene transfer systems and vector development for filamentous fungi, in: Applied Molecular Genetics of Fungi, J. F. Peberdy, et al., eds., p. 1-28, Cambridge University Press: Cambridge, and Pouwels et al, eds. (1985) Cloning Vectors. Elsevier: N.Y. (IBSN 0 444 904018).
Alternatively, the MCP proteins of the invention can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., Sf 9 cells) include the pAc series (Smith et al (1983) Mol. Cell Biol 3:2156-2165) and the pVL series (Lucklow and Summers (1989) Virology 170:31-39).
In another embodiment, the MCP proteins of the invention may be expressed in unicellular plant cells (such as algae) or in plant cells from higher plants (e.g., the spermatophytes, such as crop plants). Examples of plant expression vectors include those detailed in: Becker, D., Kemper, E., Schell, J. and Masterson, R. (1992) “New plant binary vectors with selectable markers located proximal to the left border”, Plant Mol. Biol. 20: 1195-1197; and Bevan, M. W. (1984) “Binary Agrobacterium vectors for plant transformation”, Nucl. Acid Res. 12: 8711-8721, and include pLGV23, pGHlac+, pBIN19, pAK2004, and pDH51 (Pouwels et al., eds. (1985) Cloning Vectors. Elsevier: N.Y. IBSN 0 444 904018).
In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) and pMT2PC (Kaufman et al (1987) EMBO J. 6:187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements.
For example, commonly used promoters are derived from polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see chapters 16 and 17 of Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.
In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert et al. (1987) Genes Dev. 1:268-277), lymphoid-specific promoters (Calame and Eaton (1988) Adv. Immunol. 43:235-275), in particular promoters of T cell receptors (Winoto and Baltimore (1989) EMBO J. 8:729-733) and immunoglobulins (Banerji et al. (1983) Cell 33:729-740; Queen and Baltimore (1983) Cell 33:741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle (1989) PNAS 86:5473-5477), pancreas-specific promoters (Edlund et al (1985) Science 230:912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, for example the murine hox promoters (Kessel and Gruss (1990) Science 249:374-379) and the α-fetoprotein promoter (Campes and Tilghman (1989) Genes Dev. 3:537-546).
The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively linked to a regulatory sequence in a manner which allows for expression (by transcription of the DNA molecule) of an RNA molecule which is antisense to MCP mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen which direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen which direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see Weintraub, H. et al. (1986) “Antisense RNA as a molecular tool for genetic analysis”, Reviews—Trends in Genetics, Vol. 1(1).
Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.
A host cell can be any prokaryotic or eukaryotic cell. For example, an MCP protein can be expressed in bacterial cells such as C. glutamicum, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those of ordinary skill in the art. Microorganisms related to Corynebacterium glutamicum which may be conveniently used as host cells for the nucleic acid and protein molecules of the invention are set forth in Table 3.
Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation”, “transfection”, “conjugation” and “transduction” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., linear DNA or RNA (e.g., a linearized vector or a gene construct alone without a vector) or nucleic acid in the form of a vector (e.g., a plasmid, phage, plasmid, phagemid, transposon or other DNA) into a host cell, including using natural competence, chemical mediated transfer, calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual 2nd, ed, Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.
For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Preferred selectable markers include those which confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding an MCP protein or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by, for example, drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).
To create a homologous recombinant microorganism, a vector is prepared which contains at least a portion of an MCP gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the MCP gene. Preferably, this MCP gene is a Corynebacterium glutamicum MCP gene, but it can be a homologue from a related bacterium or even from a mammalian, yeast, or insect source. In a preferred embodiment, the vector is designed such that, upon homologous recombination, the endogenous MCP gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector). Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous MCP gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous MCP protein). In the homologous recombination vector, the altered portion of the MCP gene is flanked at its 5′ and 3′ ends by additional nucleic acid of the MCP gene to allow for homologous recombination to occur between the exogenous MCP gene carried by the vector and an endogenous MCP gene in a microorganism. The additional flanking MCP nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, less than one kilobase of flanking DNA (both at the 5′ and 3′ ends) is included in the vector (see e.g., Thomas, K. R., and Capecchi, M. R. (1987) Cell 51: 503 for a description of homologous recombination vectors). The vector is introduced into a microorganism (e.g., by electroporation) and cells in which the introduced MCP gene has homologously recombined with the endogenous MCP gene are selected, using art-known techniques.
In another embodiment, recombinant microorganisms can be produced which contain selected systems which allow for regulated expression of the introduced gene. For example, inclusion of an MCP gene on a vector placing it under control of the lac operon permits expression of the MCP gene in the presence of IPTG. Such regulatory systems are well known in the art.
In another embodiment, an endogenous MCP gene in a host cell is disrupted (e.g., by homologous recombination or other genetic means known in the art) such that expression of its protein product does not occur. In another embodiment, an endogenous or introduced MCP gene in a host cell has been altered by one or more point mutations, deletions, or inversions, but still encodes a functional MCP protein. In still another embodiment, one or more of the regulatory regions (e.g., a promoter, repressor, or inducer) of an MCP gene in a microorganism has been altered (e.g., by deletion, truncation, inversion, or point mutation) such that the expression of the MCP gene is modulated. One of ordinary skill in the art will appreciate that host cells containing more than one of the described MCP gene and protein modifications may be readily produced using the methods of the invention, and are meant to be included in the present invention.
A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) an MCP protein. Accordingly, the invention further provides methods for producing MCP proteins using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding an MCP protein has been introduced, or into which genome has been introduced a gene encoding a wild-type or altered MCP protein) in a suitable medium until MCP protein is produced. In another embodiment, the method further comprises isolating MCP proteins from the medium or the host cell.
C. Isolated MCP Proteins
Another aspect of the invention pertains to isolated MCP proteins, and biologically active portions thereof. An “isolated” or “purified” protein or biologically active portion thereof is substantially free of cellular material when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of MCP protein in which the protein is separated from cellular components of the cells in which it is naturally or recombinantly produced. In one embodiment, the language “substantially free of cellular material” includes preparations of MCP protein having less than about 30% (by dry weight) of non-MCP protein (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-MCP protein, still more preferably less than about 10% of non-MCP protein, and most preferably less than about 5% non-MCP protein. When the MCP protein or biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, ie., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the protein preparation. The language “substantially free of chemical precursors or other chemicals” includes preparations of MCP protein in which the protein is separated from chemical precursors or other chemicals which are involved in the synthesis of the protein. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of MCP protein having less than about 30% (by dry weight) of chemical precursors or non-MCP chemicals, more preferably less than about 20% chemical precursors or non-MCP chemicals, still more preferably less than about 10% chemical precursors or non-MCP chemicals, and most preferably less than about 5% chemical precursors or non-MCP chemicals. In preferred embodiments, isolated proteins or biologically active portions thereof lack contaminating proteins from the same organism from which the MCP protein is derived. Typically, such proteins are produced by recombinant expression of, for example, a C. glutamicum MCP protein in a microorganism such as C. glutamicum.
An isolated MCP protein or a portion thereof of the invention is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms. In preferred embodiments, the protein or portion thereof comprises an amino acid sequence which is sufficiently homologous to an amino acid sequence of Appendix B such that the protein or portion thereof maintains the ability to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms. The portion of the protein is preferably a biologically active portion as described herein. In another preferred embodiment, an MCP protein of the invention has an amino acid sequence shown in Appendix B. In yet another preferred embodiment, the MCP protein has an amino acid sequence which is encoded by a nucleotide sequence which hybridizes, e.g., hybridizes under stringent conditions, to a nucleotide sequence of Appendix A. In still another preferred embodiment, the MCP protein has an amino acid sequence which is encoded by a nucleotide sequence that is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to one of the nucleic acid sequences of Appendix A, or a portion thereof. Ranges and identity values intermediate to the above-recited values, (e.g., 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included. The preferred MCP proteins of the present invention also preferably possess at least one of the MCP activities described herein. For example, a preferred MCP protein of the present invention includes an amino acid sequence encoded by a nucleotide sequence which hybridizes, e.g., hybridizes under stringent conditions, to a nucleotide sequence of Appendix A, and which is able to modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum, to degrade hydrocarbons, to oxidize terpenoids, to serve as a target for drug development, or to serve as an identifying marker for C. glutamicum or related organisms.
In other embodiments, the MCP protein is substantially homologous to an amino acid sequence of Appendix B and retains the functional activity of the protein of one of the sequences of Appendix B yet differs in amino acid sequence due to natural variation or mutagenesis, as described in detail in subsection I above. Accordingly, in another embodiment, the MCP protein is a protein which comprises an amino acid sequence which is at least about 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, or 60%, preferably at least about 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, more preferably at least about 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, or 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, or 90%, or 91%, 92%, 93%, 94%, and even more preferably at least about 95%, 96%, 97%, 98%, 99% or more homologous to an entire amino acid sequence of Appendix B and which has at least one of the MCP activities described herein. Ranges and identity values intermediate to the above-recited values, (e.g., 70-90% identical or 80-95% identical) are also intended to be encompassed by the present invention. For example, ranges of identity values using a combination of any of the above values recited as upper and/or lower limits are intended to be included. In another embodiment, the invention pertains to a full length C. glutamicum protein which is substantially homologous to an entire amino acid sequence of Appendix B.
Biologically active portions of an MCP protein include peptides comprising amino acid sequences derived from the amino acid sequence of an MCP protein, e.g., an amino acid sequence shown in Appendix B or the amino acid sequence of a protein homologous to an MCP protein, which include fewer amino acids than a full length MCP protein or the full length protein which is homologous to an MCP protein, and exhibit at least one activity of an MCP protein. Typically, biologically active portions (peptides, e.g., peptides which are, for example, 5, 10, 15, 20, 30, 35, 36, 37, 38, 39, 40, 50, 100 or more amino acids in length) comprise a domain or motif with at least one activity of an MCP protein. Moreover, other biologically active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the activities described herein. Preferably, the biologically active portions of an MCP protein include one or more selected domains/motifs or portions thereof having biological activity.
MCP proteins are preferably produced by recombinant DNA techniques. For example, a nucleic acid molecule encoding the protein is cloned into an expression vector (as described above), the expression vector is introduced into a host cell (as described above) and the MCP protein is expressed in the host cell. The MCP protein can then be isolated from the cells by an appropriate purification scheme using standard protein purification techniques. Alternative to recombinant expression, an MCP protein, polypeptide, or peptide can he synthesized chemically using standard peptide synthesis techniques. Moreover, native MCP protein can be isolated from cells (e.g., endothelial cells, bacterial cells, fungal cells or other cells), for example using an anti-MCP antibody, which can be produced by standard techniques utilizing an MCP protein or fragment thereof of this invention.
The invention also provides MCP chimeric or fusion proteins. As used herein, an MCP “chimeric protein” or “fusion protein” comprises an MCP polypeptide operatively linked to a non-MCP polypeptide. An “MCP polypeptide” refers to a polypeptide having an amino acid sequence corresponding to an MCP protein, whereas a “non-MCP polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein which is not substantially homologous to the MCP protein, e.g., a protein which is different from the MCP protein and which is derived from the same or a different organism. Within the fusion protein, the term “operatively linked” is intended to indicate that the MCP polypeptide and the non-MCP polypeptide are fused in-frame to each other. The non-MCP polypeptide can be fused to the N-terminus or C-terminus of the MCP polypeptide. For example, in one embodiment the fusion protein is a GST-MCP fusion protein in which the MCP sequences are fused to the C-terminus of the GST sequences. Such fusion proteins can facilitate the purification of recombinant MCP proteins. In another embodiment, the fusion protein is an MCP protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells, bacterial host cells, fungal host cells), expression and/or secretion of an MCP protein can be increased through use of a heterologous signal sequence.
Preferably, an MCP chimeric or fusion protein of the invention is produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, for example by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al. John Wiley & Sons: 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). An MCP-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the MCP protein.
Homologues of the MCP protein can be generated by mutagenesis, e.g., discrete point mutation or truncation of the MCP protein. As used herein, the term “homologue” refers to a variant form of the MCP protein which acts as an agonist or antagonist of the activity of the MCP protein. An agonist of the MCP protein can retain substantially the same, or a subset, of the biological activities of the MCP protein. An antagonist of the MCP protein can inhibit one or more of the activities of the naturally occurring form of the MCP protein, by, for example, competitively binding to a downstream or upstream member of a biochemical pathway which includes the MCP protein.
In an alternative embodiment, homologues of the MCP protein can be identified by screening combinatorial libraries of mutants, e.g., truncation mutants, of the MCP protein for MCP protein agonist or antagonist activity. In one embodiment, a variegated library of MCP variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of MCP variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential MCP sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of MCP sequences therein. There are a variety of methods which can be used to produce libraries of potential MCP homologues from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential MCP sequences. Methods for synthesizing degenerate oligonucleotides are known in the art (see, e.g., Narang, S. A. (1983) Tetrahedron 39:3; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakura et al. (1984) Science 198:1056; Ike et al. (1983) Nucleic Acid Res. 11:477.
In addition, libraries of fragments of the MCP protein coding can be used to generate a variegated population of MCP fragments for screening and subsequent selection of homologues of an MCP protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an MCP coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double stranded DNA which can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal, C-terminal and internal fragments of various sizes of the MCP protein.
Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of MCP homologues. The most widely used techniques, which are amenable to high through-put analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recrusive ensemble mutagenesis (REM), a new technique which enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify MCP homologues (Arkin and Yourvan (1992) PNAS 89:7811-7815; Delgrave et al. (1993) Protein Engineering 6(3):327-331).
In another embodiment, cell based assays can be exploited to analyze a variegated MCP library, using methods well known in the art.
D. Uses and Methods of the Invention
The nucleic acid molecules, proteins, protein homologues, fusion proteins, primers, vectors, and host cells described herein can be used in one or more of the following methods: identification of C. glutamicum and related organisms; mapping of genomes of organisms related to C. glutamicum; identification and localization of C glutamicum sequences of interest; evolutionary studies; determination of MCP protein regions required for function; modulation of an MCP protein activity; modulation of the activity of one or more metabolic pathways; and modulation of cellular production of a desired compound, such as a fine chemical.
The MCP nucleic acid molecules of the invention have a variety of uses. First, they may be used to identify an organism as being Corynebacterium glutamicum or a close relative thereof. Also, they may be used to identify the presence of C. glutamicum or a relative thereof in a mixed population of microorganisms. The invention provides the nucleic acid sequences of a number of C. glutamicum genes, and probes based thereon; by probing the extracted genomic DNA of a culture of a unique or mixed population of microorganisms under stringent conditions with a probe spanning a region of a C. glutamicum gene which is unique to this organism, one can ascertain whether this organism is present. Although Corynebacterium glutamicum itself is nonpathogenic, it is related to pathogenic species, such as Corynebacterium diphtheriae. Corynebacterium diphtheriae is the causative agent of diphtheria, a rapidly developing, acute, febrile infection which involves both local and systemic pathology. In this disease, a local lesion develops in the upper respiratory tract and involves necrotic injury to epithelial cells; the bacilli secrete toxin which is disseminated through this lesion to distal susceptible tissues of the body. Degenerative changes brought about by the inhibition of protein synthesis in these tissues, which include heart, muscle, peripheral nerves, adrenals, kidneys, liver and spleen, result in the systemic pathology of the disease. Diphtheria continues to have high incidence in many parts of the world, including Africa, Asia, Eastern Europe and the independent states of the former Soviet Union. An ongoing epidemic of diphtheria in the latter two regions has resulted in at least 5,000 deaths since 1990.
In one embodiment, the invention provides a method of identifying the presence or activity of Corynebacterium diphtheriae in a subject. This method includes detection of one or more of the nucleic acid or amino acid sequences of the invention (e.g., the sequences set forth in Appendix A or Appendix B) in a subject, thereby detecting the presence or activity of Corynebacterium diphtheriae in the subject. C. glutamicum and C. diphtheriae are related bacteria, and many of the nucleic acid and protein molecules in C. glutamicum are homologous to C. diphtheriae nucleic acid and protein molecules, and can therefore be used to detect C. diphtheriae in a subject.
To detect the presence of C. glutamicum in a sample, techniques well known in the art may be employed. Specifically, the cells in the sample may optionally first be cultured in a suitable liquid or on a suitable solid culture medium to increase the number of cells in the sample. These cells are lysed, and the total DNA content extracted and optionally purified to remove debris and protein material which may interfere with subsequent analysis. The polymerase chain reaction or a similar technique known in the art is performed (for general reference on methodologies commonly used for the amplification of nucleic acid sequences, see Mullis et al., U.S. Pat. No. 4,683,195, Mullis et al., U.S. Pat. No. 4,965,188, and Innis, M. A., and Gelfand, D. H., (1989) PCR Protocols, A guide to Methods and Applications, Academic Press, p. 3-12, and (1988) Biotechnology 6:1197, and International Patent Application No. WO89/01050) in which primers specific to an MCP nucleic acid molecule of the invention are incubated with the nucleic acid sample such that, if present in the sample, that particular MCP nucleic acid sequence will be amplified. The particular MCP nucleic acid to be amplified is selected based on its uniqueness to the C. glutamicum genome, or to the genomes of C. glutamicum and only a few closely related bacteria. The presence of the desired amplified product is thus indicative of the presence of C. glutamicum, or an organism closely related to C. glutamicum.
Further, the nucleic acid and protein molecules of the invention may serve as markers for specific regions of the genome. It is possible, using techniques well known in the art, to ascertain the physical location on the C. glutamicum genome of the MCP nucleic acid molecules of the invention, which in turn provides markers on the genome which can be used to aid in the placement of other nucleic acid molecules and genes on the genome map. Also, the nucleic acid molecules of the invention may be sufficiently homologous to the sequences of related bacterial species that these nucleic acid molecules may similarly permit the construction of a genomic map in such bacteria (e.g., Brevibacterium lactofermentum).
The nucleic acid molecules of the invention have utility not only in the mapping of the genome, but also for functional studies of C. glutamicum proteins. For example, to identify the region of the genome to which a particular C. glutamicum DNA-binding protein binds, the C. glutamicum genome could be digested, and the fragments incubated with the DNA-binding protein. Those which bind the protein may be additionally probed with the nucleic acid molecules of the invention, preferably with readily detectable labels; binding of such a nucleic acid molecule to the genome fragment enables the localization of the fragment to the genome map of C. glutamicum, and, when performed multiple times with different enzymes, facilitates a rapid determination of the nucleic acid sequence to which the protein binds.
The MCP nucleic acid molecules of the invention are also useful for evolutionary and protein structural studies. The metabolic processes in which the molecules of the invention participate are utilized by a wide variety of prokaryotic and eukaryotic cells; by comparing the sequences of the nucleic acid molecules of the present invention to those encoding similar enzymes from other organisms, the evolutionary relatedness of the organisms can be assessed. Similarly, such a comparison permits an assessment of which regions of the sequence are conserved and which are not, which may aid in determining those regions of the protein which are essential for the functioning of the enzyme. This type of determination is of value for protein engineering studies and may give an indication of what the protein can tolerate in terms of mutagenesis without losing function.
The MCP protein molecules of the invention may also be utilized as markers for the classification of an unknown bacterium as C. glutamicum, or for the identification of C. glutamicum or closely related bacteria in a sample. For example, using techniques well known in the art, cells in a sample may optionally be amplified (e.g., by culturing in an appropriate medium) to increase the sample size, and then may be lysed to release proteins contained therein. This sample may optionally be purified to remove debris and nucleic acid molecules which may interfere with subsequent analysis. Antibodies specific for a selected MCP protein of the invention may be incubated with the protein sample in a typical Western assay format (see, e.g., Ausubel et al., (1988) Current Protocols in Molecular Biology, Wiley: New York) in which the antibody will bind to its target protein if this protein is present in the sample. An MCP protein is selected for this type of assay if it is unique or nearly unique to C. glutamicum or C. glutamicum and bacteria very closely related to C. glutamicum. Proteins in the sample are then separated by gel electrophoresis, and transferred to a suitable matrix, such as nitrocellulose. An appropriate secondary antibody having a detectable label (e.g., chemiluminescent or colorimetric) is incubated with this matrix, followed by stringent washing. The presence or absence of the label is indicative of the presence or absence of the target protein in the sample. If the protein is present, then this is indicative of the presence of C. glutamicum. A similar process enables the classification of an unknown bacterium as C. glutamicum; if a panel of proteins specific to C. glutamicum are not detected in protein samples prepared from the unknown bacterium, then that bacterium is not likely to be C. glutamicum.
The invention provides methods for screening molecules which modulate the activity of an MCP protein, either by interacting with the protein itself or a substrate or binding partner of the MCP protein, or by modulating the transcription or translation of an MCP nucleic acid molecule of the invention. In such methods, a microorganism expressing one or more MCP proteins of the invention is contacted with one or more test compounds, and the effect of each test compound on the activity or level of expression of the MCP protein is assessed.
Genetic manipulation of the MCP nucleic acid molecules of the invention may result in the production of MCP proteins having functional differences from the wild-type MCP proteins. These proteins may be improved in efficiency or activity, may be present in greater numbers in the cell than is usual, or may be decreased in efficiency or activity.
Such changes in activity may directly modulate the yield, production, and/or efficiency of production of one or more fine chemicals from C. glutamicum. For example, by modifying the activity of a protein involved in the biosynthesis or degradation of a fine chemical (i.e., through mutagenesis of the corresponding gene), one may directly modulate the ability of the cell to synthesize or to degrade this compound, thereby modulating the yield and/or efficiency of production of the fine chemical. Similarly, by modulating the activity of a protein which regulates a fine chemical metabolic pathway, one may directly influence whether the production of the desired compound is up- or down-regulated, either of which will modulate the yield or efficiency of production of the fine chemical from the cell.
Indirect modulation of fine chemical production may also result by modifying the activity of a protein of the invention (i.e., by mutagenesis of the corresponding gene) such that the overall ability of the cell to grow and divide or to remain viable and productive is increased. The production of fine chemicals from C. glutamicum is generally accomplished by the large-scale fermentative culture of these microorganisms, conditions which are frequently suboptimal for growth and cell division. By engineering a protein of the invention (e.g., a stress response protein, a cell wall protein, or proteins involved in the metabolism of compounds necessary for cell growth and division to occur, such as nucleotides and amino acids) such that it is better able to survive, grow, and multiply in such conditions, it may be possible to increase the number and productivity of such engineered C. glutamicum cells in large-scale culture, which in turn should result in increased yields and/or efficiency of production of one or more desired fine chemicals. Further, the metabolic pathways of any cell are necessarily interrelated and coregulated. By altering the activity or regulation of any one metabolic pathway in C. glutamicum (i.e., by altering the activity of one of the proteins of the invention which participates in such a pathway), it is possible to concomitantly alter the activity or regulation of other metabolic pathways in this microorganism, which may be directly involved in the synthesis or degradation of a fine chemical.
The aforementioned mutagenesis strategies for MCP proteins to result in increased yields of a fine chemical from C. glutamicum are not meant to be limiting; variations on these strategies will be readily apparent to one of ordinary skill in the art. Using such strategies, and incorporating the mechanisms disclosed herein, the nucleic acid and protein molecules of the invention may be utilized to generate C. glutamicum or related strains of bacteria expressing mutated MCP nucleic acid and protein molecules such that the yield, production, and/or efficiency of production of a desired compound is improved. This desired compound may be any natural product of C. glutamicum, which includes the final products of biosynthesis pathways and intermediates of naturally-occurring metabolic pathways, as well as molecules which do not naturally occur in the metabolism of C. glutamicum, but which are produced by a C. glutamicum strain of the invention.
This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references, patent applications, patents, published patent applications, Tables, Appendices, and the sequence listing cited throughout this application are hereby incorporated by reference.
Exemplification
A culture of Corynebacterium glutamicum (ATCC 13032) was grown overnight at 30° C. with vigorous shaking in BHI medium (Difco). The cells were harvested by centrifugation, the supernatant was discarded and the cells were resuspended in 5 ml buffer-I (5% of the original volume of the culture—all indicated volumes have been calculated for 100 ml of culture volume). Composition of buffer-I: 140.34 g/l sucrose, 2.46 g/l MgSO4×7H2O, 10 ml/l KH2PO4 solution (100 g/l, adjusted to pH 6.7 with KOH), 50 ml/l M12 concentrate (10 g/l (NH)2SO4, 1 g/l NaCl, 2 g/l MgSO4×7H2O, 0.2 μl CaCl2, 0.5 g/l yeast extract (Difco), 10 ml/l trace-elements-mix (200 mg/l FeSO4×H2O, 10 mg/l ZnSO4×7H2O, 3 mg/l MnCl2×4 H2O, 30 mg/l H2BO3 20 mg/l CoCl2×6H2O, 1 mg/l NiCl2×6H2O, 3 mg/l Na2MoO4×2H2O, 500 mg/l complexing agent (EDTA or critic acid), 100 ml/l vitamins-mix (0.2 mg/l biotin, 0.2 mg/l folic acid, 20 mg/l p-amino benzoic acid, 20 mg/l riboflavin, 40 mg/l α-panthothenate, 140 mg/l nicotinic acid, 40 mg/l pyridoxole hydrochloride, 200 mg/l myo-inositol). Lysozyme was added to the suspension to a final concentration of 2.5 mg/ml. After an approximately 4 h incubation at 37° C., the cell wall was degraded and the resulting protoplasts are harvested by centrifugation. The pellet was washed once with 5 ml buffer-I and once with 5 ml TE-buffer (10 mM Tris-HCl, 1 mM EDTA, pH 8). The pellet was resuspended in 4 ml TE-buffer and 0.5 ml SDS solution (10%) and 0.5 ml NaCl solution (5 M) are added. After adding of proteinase K to a final concentration of 200 μg/ml, the suspension is incubated for ca. 18 h at 37° C. The DNA was purified by extraction with phenol, phenol-chloroform-isoamylalcohol and chloroform-isoamylalcohol using standard procedures. Then, the DNA was precipitated by adding 1/50 volume of 3 M sodium acetate and 2 volumes of ethanol, followed by a 30 min incubation at −20° C. and a 30 min centrifugation at 12,000 rpm in a high speed centrifuge using a SS34 rotor (Sorvall). The DNA was dissolved in 1 ml TE-buffer containing 20 μg/ml RNaseA and dialysed at 4° C. against 1000 ml TE-buffer for at least 3 hours. During this time, the buffer was exchanged 3 times. To aliquots of 0.4 ml of the dialysed DNA solution, 0.4 ml of 2 M LiCl and 0.8 ml of ethanol are added. After a 30 min incubation at −20° C., the DNA was collected by centrifigation (13,000 rpm, Biofuge Fresco, Heraeus, Hanau, Germany). The DNA pellet was dissolved in TE-buffer. DNA prepared by this procedure could be used for all purposes, including southern blotting or construction of genomic libraries.
Using DNA prepared as described in Example 1, cosmid and plasmid libraries were constructed according to known and well established methods (see e.g., Sambrook, J. et al. (1989) “Molecular Cloning: A Laboratory Manual”, Cold Spring Harbor Laboratory Press, or Ausubel, F. M. et al. (1994) “Current Protocols in Molecular Biology”, John Wiley & Sons.)
Any plasmid or cosmid could be used. Of particular use were the plasmids pBR322 (Sutcliffe, J. G. (1979) Proc. Natl. Acad. Sci. USA, 75:3737-3741); PACYC177 (Change & Cohen (1978) J. Bacteriol 134:1141-1156), plasmids of the pBS series (pBSSK+, pBSSK− and others; Stratagene, LaJolla, USA), or cosmids as SuperCos1 (Stratagene, LaJolla, USA) or Lorist6 (Gibson, T. J., Rosenthal A. and Waterson, R. H. (1987) Gene 53:283-286. Gene libraries specifically for use in C. glutamicum may be constructed using plasmid pSLI09 (Lee, H.-S. and A. J. Sinskey (1994) J. Microbiol. Biotechnol. 4: 256-263).
Genomic libraries as described in Example 2 were used for DNA sequencing according to standard methods, in particular by the chain termination method using ABI377 sequencing machines (see e.g., Fleischman, R. D. et al. (1995) “Whole-genome Random Sequencing and Assembly of Haemophilus Influenzae Rd., Science, 269:496-512). Sequencing primers with the following nucleotide sequences were used: 5′-GGAAACAGTATGACCATG-3′ (SEQ ID NO:2933) or 5′-GTAAAACGACGGCCAGT-3′ (SEQ ID NO:2934).
In vivo mutagenesis of Corynebacterium glutamicum can be performed by passage of plasmid (or other vector) DNA through E. coli or other microorganisms (e.g. Bacillus spp. or yeasts such as Saccharomyces cerevisiae) which are impaired in their capabilities to maintain the integrity of their genetic information. Typical mutator strains have mutations in the genes for the DNA repair system (e.g., mutHLS, mutD, mutT, etc.; for reference, see Rupp, W. D. (1996) DNA repair mechanisms, in: Escherichia coli and Salmonella, p. 2277-2294, ASM: Washington.) Such strains are well known to those of ordinary skill in the art. The use of such strains is illustrated, for example, in Greener, A. and Callahan, M. (1994) Strategies 7: 32-34.
Several Corynebacterium and Brevibacterium species contain endogenous plasmids (as e.g., pHM 1519 or pBL1) which replicate autonomously (for review see, e.g., Martin, J. F. et al. (1987) Biotechnology, 5: 137-146). Shuttle vectors for Escherichia coli and Corynebacterium glutamicum can be readily constructed by using standard vectors for E. coli(Sambrook, J. et al. (989), “Molecular Cloning: A Laboratory Manual”, Cold Spring Harbor Laboratory Press or Ausubel, F. M. et al. (1994) “Current Protocols in Molecular Biology”, John Wiley & Sons) to which a origin or replication for and a suitable marker from Corynebacterium glutamicum is added. Such origins of replication are preferably taken from endogenous plasmids isolated from Corynebacterium and Brevibacterium species. Of particular use as transformation markers for these species are genes for kanamycin resistance (such as those derived from the Tn5 or Tn903 transposons) or chloramphenicol (Winnacker, E. L. (1987) “From Genes to Clones—Introduction to Gene Technology, VCH, Weinheim). There are numerous examples in the literature of the construction of a wide variety of shuttle vectors which replicate in both E. coli and C. glutamicum, and which can be used for several purposes, including gene overexpression (for reference, see e.g., Yoshihama, M. et al. (1985) J. Bacteriol. 162:591-597, Martin J. F. et al. (1987) Biotechnology, 5:137-146 and Eikmanns, B. J et al. (1991) Gene, 102:93-98).
Using standard methods, it is possible to clone a gene of interest into one of the shuttle vectors described above and to introduce such a hybrid vectors into strains of Corynebacterium glutamicum. Transformation of C. glutamicum can be achieved by protoplast transformation (Kastsumata, R. et al. (1984) J. Bacteriol. 159306-311), electroporation (Liebl, E. et al. (1989) FEMS Microbiol. Letters, 53:399-303) and in cases where special vectors are used, also by conjugation (as described e.g. in Schäfer, A et al. (1990) J. Bacteriol. 172:1663-1666). It is also possible to transfer the shuttle vectors for C glutamicum to E. coli by preparing plasmid DNA from C. glutamicum (using standard methods well-known in the art) and transforming it into E. coli. This transformation step can be performed using standard methods, but it is advantageous to use an Mcr-deficient E. coli strain, such as NM522 (Gough & Murray (1983) J. Mol. Biol. 166:1-19).
Genes may be overexpressed in C. glutamicum stains using plasmids which comprise pCG1 (U.S. Pat. No. 4,617,267) or fragments thereof, and optionally the gene for kanamycin resistance from TN903 (Grindley, N. D. and Joyce, C. M. (1980) Proc. Nat. Acad. Sci. USA 77(12): 7176-7180). In addition, genes may be overexpressed in C. glutamicum strains using plasmid pSL109 (Lee, H.-S. and A. J. Sinskey (1994) J. Microbiol Biotechnol. 4: 256-263).
Aside from the use of replicative plasmids, gene overexpression can also be achieved by integration into the genome. Genomic integration in C. glutamicum or other Corynebacterium or Brevibacterium species may be accomplished by well-known methods, such as homologous recombination with genomic region(s), restriction endonuclease mediated integration (REMI) (see, e.g., DE Patent 19823834), or through the use of transposons. It is also possible to modulate the activity of a gene of interest by modifying the regulatory regions (e.g., a promoter, a repressor, and/or an enhancer) by sequence modification, insertion, or deletion using site-directed methods (such as homologous recombination) or methods based on random events (such as transposon mutagenesis or REMI). Nucleic acid sequences which function as transcriptional terminators may also be inserted 3′ to the coding region of one or more genes of the invention; such terminators are well-known in the art and are described, for example, in Winnacker, E. L. (1987) From Genes to Clones—Introduction to Gene Technology. VCH: Weinheim.
Observations of the activity of a mutated protein in a transformed host cell rely on the fact that the mutant protein is expressed in a similar fashion and in a similar quantity to that of the wild-type protein. A useful method to ascertain the level of transcription of the mutant gene (an indicator of the amount of mRNA available for translation to the gene product) is to perform a Northern blot (for reference see, for example, Ausubel et al. (1988) Current Protocols in Molecular Biology, Wiley: New York), in which a primer designed to bind to the gene of interest is labeled with a detectable tag (usually radioactive or chemiluminescent), such that when the total RNA of a culture of the organism is extracted, run on gel, transferred to a stable matrix and incubated with this probe, the binding and quantity of binding of the probe indicates the presence and also the quantity of mRNA for this gene. This information is evidence of the degree of transcription of the mutant gene. Total cellular RNA can be prepared from Corynebacterium glutamicum by several methods, all well-known in the art, such as that described in Bormann, E. R. et al. (1992) Mol. Microbiol. 6: 317-326.
To assess the presence or relative quantity of protein translated from this mRNA, standard techniques, such as a Western blot, may be employed (see, for example, Ausubel et al. (1988) Current Protocols in Molecular Biology, Wiley: New York). In this process, total cellular proteins are extracted, separated by gel electrophoresis, transferred to a matrix such as nitrocellulose, and incubated with a probe, such as an antibody, which specifically binds to the desired protein. This probe is generally tagged with a chemiluminescent or calorimetric label which may be readily detected. The presence and quantity of label observed indicates the presence and quantity of the desired mutant protein present in the cell.
Genetically modified Corynebacteria are cultured in synthetic or natural growth media. A number of different growth media for Corynebacteria are both well-known and readily available (Lieb et al. (1989) Appl. Microbiol. Biotechnol., 32:205-210; von der Osten et al. (1998) Biotechnology Letters, 11:11-16; Patent DE 4,120,867; Liebl (1992) “The Genus Corynebacterium, in: The Procaryotes, Volume II, Balows, A. et al., eds. Springer-Verlag). These media consist of one or more carbon sources, nitrogen sources, inorganic salts, vitamins and trace elements. Preferred carbon sources are sugars, such as mono-, di-, or polysaccharides. For example, glucose, fructose, mannose, galactose, ribose, sorbose, ribulose, lactose, maltose, sucrose, raffinose, starch or cellulose serve as very good carbon sources. It is also possible to supply sugar to the media via complex compounds such as molasses or other by-products from sugar refinement. It can also be advantageous to supply mixtures of different carbon sources. Other possible carbon sources are alcohols and organic acids, such as methanol, ethanol, acetic acid or lactic acid. Nitrogen sources are usually organic or inorganic nitrogen compounds, or materials which contain these compounds. Exemplary nitrogen sources include ammonia gas or ammonia salts, such as NH4CI or (NH4)2SO4, NH4OH, nitrates, urea, amino acids or complex nitrogen sources like corn steep liquor, soy bean flour, soy bean protein, yeast extract, meat extract and others.
Inorganic salt compounds which may be included in the media include the chloride-, phosphorous- or sulfate- salts of calcium, magnesium, sodium, cobalt, molybdenum, potassium, manganese, zinc, copper and iron. Chelating compounds can be added to the medium to keep the metal ions in solution. Particularly useful chelating compounds include dihydroxyphenols, like catechol or protocatechuate, or organic acids, such as citric acid. It is typical for the media to also contain other growth factors, such as vitamins or growth promoters, examples of which include biotin, riboflavin, thiamin, folic acid, nicotinic acid, pantothenate and pyridoxin. Growth factors and salts frequently originate from complex media components such as yeast extract, molasses, corn steep liquor and others. The exact composition of the media compounds depends strongly on the immediate experiment and is individually decided for each specific case. Information about media optimization is available in the textbook “Applied Microbiol. Physiology, A Practical Approach (eds. P. M. Rhodes, P. F. Stanbury, IRL Press (1997) pp. 53-73, ISBN 0 19 963577 3). It is also possible to select growth media from commercial suppliers, like standard I (Merck) or BHI (grain heart infusion, DIFCO) or others.
All medium components are sterilized, either by heat (20 minutes at 1.5 bar and 121° C.) or by sterile filtration. The components can either be sterilized together or, if necessary, separately. All media components can be present at the beginning of growth, or they can optionally be added continuously or batchwise.
Culture conditions are defined separately for each experiment. The temperature should be in a range between 15° C. and 45° C. The temperature can be kept constant or can be altered during the experiment. The pH of the medium should be in the range of 5 to 8.5, preferably around 7.0, and can be maintained by the addition of buffers to the media. An exemplary buffer for this purpose is a potassium phosphate buffer. Synthetic buffers such as MOPS, HEPES, ACES and others can alternatively or simultaneously be used. It is also possible to maintain a constant culture pH through the addition of NaOH or NH4OH during growth. If complex medium components such as yeast extract are utilized, the necessity for additional buffers may be reduced, due to the fact that many complex compounds have high buffer capacities. If a fermentor is utilized for culturing the microorganisms, the pH can also be controlled using gaseous ammonia.
The incubation time is usually in a range from several hours to several days. This time is selected in order to permit the maximal amount of product to accumulate in the broth. The disclosed growth experiments can be carried out in a variety of vessels, such as microtiter plates, glass tubes, glass flasks or glass or metal fermentors of different sizes. For screening a large number of clones, the microorganisms should be cultured in microtiter plates, glass tubes or shake flasks, either with or without baffles. Preferably 100 ml shake flasks are used, filled with 10% (by volume) of the required growth medium. The flasks should be shaken on a rotary shaker (amplitude 25 mm) using a speed-range of 100-300 rpm. Evaporation losses can be diminished by the maintenance 110 of a humid atmosphere; alternatively, a mathematical correction for evaporation losses should be performed.
If genetically modified clones are tested, an unmodified control clone or a control clone containing the basic plasmid without any insert should also be tested. The medium is inoculated to an OD600 of 0.5-1.5 using cells grown on agar plates, such as CM plates (10 g/l glucose, 2,5 g/l NaCl, 2 g/l urea, 10 g/l polypeptone, 5 g/l yeast extract, 5 g/l meat extract, 22 g/l NaCl, 2 g/l urea, 10 g/l polypeptone, 5 μl yeast extract, 5 gll meat extract, 22 g/l agar, pH 6.8 with 2M NaOH) that had been incubated at 30° C. Inoculation of the media is accomplished by either introduction of a saline suspension of C. glutamicum cells from CM plates or addition of a liquid preculture of this bacterium.
The determination of activities and kinetic parameters of enzymes is well established in the art. Experiments to determine the activity of any given altered enzyme must be tailored to the specific activity of the wild-type enzyme, which is well within the ability of one of ordinary skill in the art. Overviews about enzymes in general, as well as specific details concerning structure, kinetics, principles, methods, applications and examples for the determination of many enzyme activities may be found, for example, in the following references: Dixon, M., and Webb, E. C., (1979) Enzymes. Longmans: London; Fersht, (1985) Enzyme Structure and Mechanism. Freeman: New York; Walsh, (1979) Enzymatic Reaction Mechanisms. Freeman: San Francisco; Price, N. C., Stevens, L. (1982) Fundamentals of Enzymology. Oxford Univ. Press: Oxford; Boyer, P. D., ed. (1983) The Enzymes, 3td ed. Academic Press: New York; Bisswanger, H., (1994) Enzymkinetik, 2nd ed. VCH: Weinheim (ISBN 3527300325); Bergmeyer, H. U., Bergmeyer, J., Graβl, M., eds. (1983-1986) Methods of Enzymatic Analysis, 3rd ed., vol. I-XII, Verlag Chemie: Weinheim; and Ullmann's Encyclopedia of Industrial Chemistry (1987) vol. A9, “Enzymes”. VCH: Weinheim, p. 352-363.
The activity of proteins which bind to DNA can be measured by several well-established methods, such as DNA band-shift assays (also called gel retardation assays). The effect of such proteins on the expression of other molecules can be measured using reporter gene assays (such as that described in Kolmar, H. et al. (1995) EMBO J. 14: 3895-3904 and references cited therein). Reporter gene test systems are well known and established for applications in both pro- and eukaryotic cells, using enzymes such as beta-galactosidase, green fluorescent protein, and several others.
The determination of activity of membrane-transport proteins can be performed according to techniques such as those described in Gennis, R. B. (1989) “Pores, Channels and Transporters”, in Biomembranes, Molecular Structure and Function, Springer: Heidelberg, p. 85-137; 199-234; and 270-322.
The effect of the genetic modification in C. glutamicum on production of a desired compound (such as an amino acid) can be assessed by growing the modified microorganism under suitable conditions (such as those described above) and analyzing the medium and/or the cellular component for increased production of the desired product (i.e., an amino acid). Such analysis techniques are well known to one of ordinary skill in the art, and include spectroscopy, thin layer chromatography, staining methods of various kinds, enzymatic and microbiological methods, and analytical chromatography such as high performance liquid chromatography (see, for example, Ullman, Encyclopedia of Industrial Chemistry, vol. A2, p. 89-90 and p. 443-613, VCH: Weinheim (1985); Fallon, A. et al., (1987) “Applications of HPLC in Biochemistry” in: Laboratory Techniques in Biochemistry and Molecular Biology, vol. 17; Rehm et al. (1993) Biotechnology, vol. 3, Chapter III: “Product recovery and purification”, page 469-714, VCH: Weinheim; Belter, P. A. et al. (1988) Bioseparations: downstream process ing for biotechnology, John Wiley and Sons; Kennedy, J. F. and Cabral, J. M. S. (1992) Recovery processes for biological materials, John Wiley and Sons; Shaeiwitz, J. A. and Henry, J. D. (1988) Biochemical separations, in: Ulmann's Encyclopedia of Industrial Chemistry, vol. B3, Chapter 11, page 1-27, VCH: Weinheim; and Dechow, F. J. (1989) Separation and purification techniques in biotechnology, Noyes. Publications.)
In addition to the measurement of the final product of fermentation, it is also possible to analyze other components of the metabolic pathways utilized for the production of the desired compound, such as intermediates and side-products, to determine the overall efficiency of production of the compound. Analysis methods include measurements of nutrient levels in the medium (e.g., sugars, hydrocarbons, nitrogen sources, phosphate, and other ions), measurements of biomass composition and growth analysis of the production of common metabolites of biosynthetic pathways, and measurement of gasses produced during fermentation. Standard methods for these measurements are outlined in Applied Microbial Physiology, A Practical Approach, P. M. Rhodes and P. F. Stanbury, eds., IRL Press, p. 103-129; 131-163; and 165-192 (ISBN: 0199635773) and references cited therein.
Recovery of the desired product from the C. glutamicum cells or supernatant of the above-described culture an be performed by various methods well known in the art. If the desired product is not secreted from the cells, the cells can be harvested from the culture by low-speed centrifugation, the cells can be lysed by standard techniques, such as mechanical force or sonication. The cellular debris is removed by centrifugation, and the supernatant fraction containing the soluble proteins is retained for further purification of the desired compound. If the product is secreted from the C. glutamicum cells, then the cells are removed from the culture by low-speed centrifugation, and the supernate fraction is retained for further purification.
The supernatant fraction from either purification method is subjected to chromatography with a suitable resin, in which the de sired molecule is either retained on a chromatography resin while many of the impurities in the sample are not, or where the impurities are retained by the resin while the sample is not. Such chromatography steps may be repeated as necessary, using the same or different chromatography resins. One of ordinary skill in the art would be well-versed in the selection of appropriate chromatography resins and in their most efficacious application for a particular molecule to be purified. The purified product may be concentrated by filtration or ultrafiltration, and stored at a temperature at which the stability of the product is maximized.
There are a wide array of purification methods known to the art and the preceding method of purification is not meant to be limiting. Such purification techniques are described, for example, in Bailey, J. E. & Ollis, D. F. Biochemical Engineering Fundamentals, McGraw-Hill: New York (1986).
The identity and purity of the isolated compounds may be assessed by techniques standard in the art. These include high-performance liquid chromatography (HPLC), spectroscopic methods, staining methods, thin layer chromatography, NIRS, enzymatic assay, or microbiologically. Such analysis methods are reviewed in; Patek et al. (1994) Appl. Environ. Microbiol. 60:133-140; Malakhova et al. (1996) Biotekhnologiya 11: 27-32; and Schmidt et al. (1998) Bioprocess Engineer. 19: 67-70. Ulmann's Encyclopedia of Industrial Chemistry, (1996) vol. A27, VCH: Weinheim, p. 89-90, p. 521-540, p. 540-547, p. 559-566, 575-581 and p. 581-587; Michal, G. (1999) Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology, John Wiley and Sons; Fallon, A. et al. (1987) Applications of HPLC in Biochemistry in: Laboratory Techniques in Biochemistry and Molecular Biology, vol. 17.
The comparison of sequences and determination of percent homology between two sequences are art-known techniques, and can be accomplished using a mathematical algorithm, such as the algorithm of Karlin and Altschul (1990) Proc. Natl. Acad. Sci. USA 87:2264-68, modified as in Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-77. Such an algorithm is incorporated into the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score=100, wordlength=12 to obtain nucleotide sequences homologous to MCP nucleic acid molecules of the invention BLAST protein searches can be performed with the XBLAST program, score=50, wordlength=3 to obtain amino acid sequences homologous to MCP protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, one of ordinary skill in the art will know how to optimize the parameters of the program (e.g., XBLAST and NBLAST) for the specific sequence being analyzed.
Another example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Meyers and Miller ((1988) Comput. Appl Biosci. 4: 11-17). Such an algorithm is incorporated into the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM 120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. Additional algorithms for sequence analysis are known in the art, and include ADVANCE and ADAM. described in Torelli and Robotti (1994) Comput. Appl. Biosci. 10:3-5; and FASTA, described in Pearson and Lipman (1988) P. N. A. S. 85:2444-8.
The percent homology between two amino acid sequences can also be accomplished using the GAP program in the GCG software package (available at the Accelrys™ website), using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 12, 10, 8, 6, or 4 and a length weight of 2, 3, or 4. The percent homology between two nucleic acid sequences can be accomplished using the GAP program in the GCG software package, using standard parameters, such as a gap weight of 50 and a length weight of 3.
A comparative analysis of the gene sequences of the invention with those present in Genbank has been performed using techniques known in the art (see, e.g., Bexevanis and Ouellette, eds. (11998) Boinformatics: A Practical Guide to the Analysis of Genes and Proteins. John Wiley and Sons: New York). The gene sequences of the invention were compared to genes present in Genbank in a three-step process. In a first step, a BLASTN analysis (e.g., a local alignment analysis) was performed for each of the sequences of the invention against the nucleotide sequences present in Genbank, and the top 500 hits were retained for further analysis. A subsequent FASTA search (e.g., a combined local and global alignment analysis, in which limited regions of the sequences are aligned) was performed on these 500 hits. Each gene sequence of the invention was subsequently globally aligned to each of the top three FASTA hits, using the GAP program in the GCG software package (using standard parameters). In order to obtain correct results, the length of the sequences extracted from Genbank were adjusted to the length of the query sequences by methods well-known in the art. The results of this analysis are set forth in Table 4. The resulting data is identical to that which would have been obtained had a GAP (global) analysis alone been performed on each of the genes of the invention in comparison with each of the references in Genbank, but required significantly reduced computational time as compared to such a database-wide GAP (global) analysis. Sequences of the invention for which no alignments above the cutoff values were obtained are indicated on Table 4 by the absence of alignment information. It will further be understood by one of ordinary skill in the art that the GAP alignment homology percentages set forth in Table 4 under the heading “% homology (GAP)” are listed in the European numerical format, wherein a ‘,’ represents a decimal point. For example a value of “40,345” in this column represents “40.345%”.
The sequences of the invention may additionally be used in the construction and application of DNA microarrays (the design, method ology, and uses of DNA arrays are well known in the art, and are described, for example, in Schena, M. et al. (1995) Science 270: 467-470; Wodicka, L. et al. (1997) Nature Biotechnology 15: 1359-1367; DeSaizieu, A. et al. (1998) Nature Biotechnology 16: 45-48; and DeRisi, J. L. et al. (1997) Science 278: 680-686).
DNA microarrays are solid or flexible supports consisting of nitrocellulose, nylon, glass, silicone, or other materials. Nucleic acid molecules may be attached to the surface in an ordered manner. After appropriate labeling, other nucleic acids or nucleic acid mixtures can be hybridized to the immobilized nucleic acid molecules, and the label may be used to monitor and measure the individual signal intensities of the hybridized molecules at defined regions. This methodology allows the simultaneous quantification of the relative or absolute amount of all or selected nucleic acids in the applied nucleic acid sample or mixture. DNA microarrays, therefore, permit an analysis of the expression of multiple (as many as 6800 or more) nucleic acids in parallel (see, e.g., Schena, M. (1996) BioEssays 18(5): 427431).
The sequences of the invention may be used to design oligonucleotide primers which are able to amplify defined regions of one or more C. glutamicum genes by a nucleic acid amplification reaction such as the polymerase chain reaction. The choice and design of the 5′ or 3′ oligonucleotide primers or of appropriate linkers allows the covalent attachment of the resulting PCR products to the surface of a support medium described above (and also described, for example, Schena, M. et al. (1995) Science 270: 467-470).
Nucleic acid microarrays may also be constructed by in situ oligonucleotide synthesis as described by Wodicka, L. et al. (1997) Nature Biotechnology 15: 1359-1367. By photolithographic methods, precisely defined regions of the matrix are exposed to light. Protective groups which are photolabile are thereby activated and undergo nucleotide addition, whereas regions that are masked from light do not undergo any modification. Subsequent cycles of protection and light activation permit the synthesis of different oligonucleotides at defined positions. Small, defined regions of the genes of the invention may be synthesized on microarrays by solid phase oligonucleotide synthesis.
The nucleic acid molecules of the invention present in a sample or mixture of nucleotides may be hybridized to the microarrays. These nucleic acid molecules can be labeled according to standard methods. In brief, nucleic acid molecules (e.g., mRNA molecules or DNA molecules) are labeled by the incorporation of isotopically or fluorescently labeled nucleotides, e.g., during reverse transcription or DNA synthesis. Hybridization of labeled nucleic acids to microarrays is described (e.g., in Schena, M. et al. (1995) supra; Wodicka, L. et al. (1997), supra; and DeSaizieu A. et al. (1998), supra). The detection and quantification of the hybridized molecule are tailored to the specific incorporated label. Radioactive labels can be detected, for example, as described in Schena, M. et al. (1995) supra) and fluorescent labels may be detected, for example, by the method of Shalon et al. (1996) Genome Research 6: 639-645).
The application of the sequences of the invention to DNA microarray technology, as described above, permits comparative analyses of different strains of C. glutamicum or other Corynebacteria. For example, studies of inter-strain variations based on individual transcript profiles and the identification of genes that are important for specific and/or desired strain properties such as pathogen icity, productivity and stress tolerance are facilitated by nucleic acid array methodologies. Also, comparisons of the profile of expression of genes of the invention during the course of a fermentation reaction are possible using nucleic acid array technology.
The genes, compositions, and methods of the invention may be applied to study the interactions and dynamics of populations of proteins, termed ‘proteomics’. Protein populations of interest include, but are not limited to, the total protein population of C. glutamicum (e.g., in comparison with the protein populations of other organisms), those proteins which are active under specific environmental or metabolic conditions (e.g., during fermentation, at high or low temperature, or at high or low pH), or those proteins which are active during specific phases of growth and development.
Protein populations can be analyzed by various well-known techniques, such as gel electrophoresis. Cellular proteins may be obtained, for example, by lysis or extraction, and may be separated from one another using a variety of electrophoretic techniques. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) separates proteins largely on the basis of their molecular weight. Isoelectric focusing polyacrylamide gel electrophoresis (IEF-PAGE) separates proteins by their isoelectric point (which reflects not only the amino acid sequence but also posttranslational modifications of the protein). Another, more preferred method of protein analysis is the consecutive combination of both IEF-PAGE and SDS-PAGE, known as 2-D-gel electrophoresis (described, for example, in Hermann et al. (1998) Electrophoresis 19: 3217-3221; Fountoulakis et al. (1998) Electrophoresis 19: 1193-1202; Langen et al. (1997) Electrophoresis 18: 1184-1192; Antelmann et al. (1997) Electrophoresis 18: 1451-1463). Other separation techniques may also be utilized for protein separation, such as capillary gel electrophoresis; such techniques are well known in the art. Proteins separated by these methodologies can be visualized by standard techniques, such as by staining or labeling. Suitable stains are known in the art, and include Coomassie Brilliant Blue, silver stain, or fluorescent dyes such as Sypro Ruby (Molecular Probes). The inclusion of radioactively labeled amino acids or other protein precursors (e.g., 35S-methionine, 35S-cysteine, 14C-labelled amino acids, 15N-amino acids, 15NO3 or 15NH4+ or 13C-labelled amino acids) in the medium of C. glutamicum permits the labeling of proteins from these cells prior to their separation. Similarly, fluorescent labels may be employed. These labeled proteins can be extracted, isolated and separated according to the previously described techniques.
Proteins visualized by these techniques can be further analyzed by measuring the amount of dye or label used. The amount of a given protein can be determined quantitatively using, for example, optical methods and can be compared to the amount of other proteins in the same gel or in other gels. Comparisons of proteins on gels can be made, for example, by optical comparison, by spectroscopy, by image scanning and analysis of gels, or through the use of photographic films and screens. Such techniques are well-known in the art.
To determine the identity of any given protein, direct sequencing or other standard techniques may be employed. For example, N- and/or C-terminal amino acid sequencing (such as Edman degradation) may be used, as may mass spectrometry (in particular MALDI or ESI techniques (see, e.g., Langen. et al. (1997) Electrophoresis 18: 1 184-1192)). The protein sequences provided herein can be used for the identification of C. glutamicum proteins by these techniques.
The information obtained by these methods can be used to compare patterns of protein presence, activity, or modification between different samples from various biological conditions (e.g., different organisms, time points of fermentation, media conditions, or different biotopes, among others). Data obtained from such experiments alone, or in combination with other techniques, can be used for various applications, such as to compare the behavior of various organisms in a given (e.g., metabolic) situation, to increase the productivity of strains which produce fine chemicals or to increase the efficiency of the production of fine chemicals.
Equivalents
Those of ordinary skill in the art will recognize, or will be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
lactofermentum,” Biosci. Biotechnol. Biochem., 60(10):1565-1570 (1996)
glutamicum,” Eur. J. Biochem., 254(2):395-403 (1998)
glutamicum 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase gene,”
glutamicum mannose enzyme II and analyses of the deduced protein
Corynebacterium glutamicum,” Appl. Environ. Microbiol., 60(7):2501-2507
lactofermentum,” J. Bacteriol., 177(2):465-467 (1995)
Corynebacterium glutamicum pheA gene,” J. Bacteriol., 167:695-702 (1986)
Brevibacterium lactofermentum, a glutamic-acid-producing bacterium,” Gene,
Brevibacterium lactfermentun, a glutamic-acid-producing bacterium,” Gene,
glutamicum ATCC13032,” Gene, 77(2):237-251 (1989)
Corynebacterium glutamicum ATCC 13032 is directed by the brnQ gene
Corynebacterium glutamicum ATCC 21850 tpD gene.” Thesis, Microbiology
coli,” J. Bacteriol., 176(23):7309-7319 (1994); Schafer, A. et al. “The
Corynebacterium glutamicum cglIM gene encoding a 5-cytosine in an McrBC-
Corynebacterium glutamicum,” Gene, 175:15-22 (1996)
Corynebacterium glutamicum unidentified
glutamicum and possible mechanisms for modulation of its expression,” Mol.
Corynebacterium glutamicum: Molecular cloning, nucleotide sequence, and
Corynebacterium glutamicum,” Nucleic Acids Res., 18(21):6421 (1990)
Corynebacterium diptheriae, Corynebacterium ulcerans, Corynebacterium
glutamicum, and the attP site of lambdacorynephage,” FEMS. Microbiol,
Corynebacterium diphtheriae, Corynebacterium ulcerans, Corynebacterium
glutamicum, and the attP site of lambdacorynephage,” FEMS. Micorbiol,
Corynebacterium glutamicum,” Mol. Gen. Genet., 224(3): 317-324 (1990)
Corynebacterium glutamicum gene cluster enoding the three glycolytic
glutamicum lysl gene involved in lysine uptake,” Mol. Microbiol., 5(12):2995-
Corynebacterium glutamicum encoding resistance to 5-methyltryptophan,”
Corynebacterium glutamicum and biochemical analysis of the enzyme,” J.
Corynebacterium glutamicum,” DNA Seq., 4(6):403-404 (1994)
Norcardia and evidence for the evolutionary origin of the genus Norcardia
Corynebacterium glutamicum complementing dapE of Escherichia coli,”
Corynebacterium glutamicumproline reveals the presence of aroP, which
Corynebacterium glutamicum betP gene, encoding the transport system for the
Corynebacterium glutamicum hom-thrB operon,” Mol. Microbiol., 2(1):63-72
glutamicumproline and characterization of a low-affinity uptake system for
glutamicum: characterization, expression and inactivation of the pyc gene,”
glutamicum,” Appl. Microbiol. Biotechnol., 50(1):42-47 (1998)
Brevibacterium lactofermentum encodes dihydrodipicolinate reductase, and a
lactofermentum: Characterization of sigA and sigB,” J. Bacteriol., 178(2):550-
Brevibacterium lactofermentum is coupled transcriptionally to the dmdR
lactofermentum: Characterization of sigA and sigB,” J. Bacteriol., 178(2):550-
iA sequence for this gene was published in the indicated reference. However, the sequence obtained by the inventors of the present application is significantly longer than the published version. It is believed that the published version relied on an incorrect start codon, and thus represents only a fragment of the actual coding region.
Corynebacterium and Brevibacterium Strains Which May be Used in the Practice of the Invention
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
ammoniagenes
Brevibacterium
butanicum
Brevibacterium
divaricatum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
flavum
Brevibacterium
healii
Brevibacterium
ketoglutamicum
Brevibacterium
ketoglutamicum
Brevibacterium
ketosoreductum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
lactofermentum
Brevibacterium
linens
Brevibacterium
linens
Brevibacterium
linens
Brevibacterium
paraffinolyticum
Brevibacterium
Brevibacterium
Brevibacterium
Brevibacterium
Brevibacterium
Brevibacterium
Brevibacterium
Brevibacterium
Corynebacterium
acetoacidophilum
Corynebacterium
acetoacidophilum
Corynebacterium
acetoglutamicum
Corynebacterium
acetoglutamicum
Corynebacterium
acetoglutamicum
Corynebacterium
acetoglutamicum
Corynebacterium
acetoglutamicum
Corynebacterium
acetophilum
Corynebacterium
ammoniagenes
Corynebacterium
ammoniagenes
Corynebacterium
fujiokense
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
lilium
Corynebacterium
nitrilophilus
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Corynebacterium
Mycoplasma pneumoniae section 13 of 63 of the complete genome.
Mycoplasma pneumoniae
Mycoplasma pneumoniae section 13 of 63 of the complete genome.
Mycoplasma pneumoniae
Drosophila melanogaster chromosome 2 clone BACR24H09 (D595) RPCI-98 24.H.9 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR24H09 (D595) RPCI-98 24.H.9 map
Drosophila melanogaster
Caenorhabditis elegans
elegans cDNA clone yk627f12 5′, mRNA sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Treponema pallidum section 86 of 87 of the complete genome.
Treponema pallidum
Leishmania major Friedlin cosmid L2385, complete sequence.
Leishmania major
Homo sapiens clone UWGC:djs58 from 7p14-15, complete sequence.
Homo sapiens
Homo sapiens clone DJ1145A24, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone DJ1145A24, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 21q22.2 cosmid Q13F10, complete sequence.
Homo sapiens
Homo sapiens
Arabidopsis thaliana
Homo sapiens, ***SEQUENCING IN PROGRESS***, 40 unordered pieces.
Homo sapiens
Homo sapiens, ***SEQUENCING IN PROGRESS***, 40 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
S. pombe chromosome II cosmid c725.
Schizosaccharomyces
pombe
Homo sapiens
Homo sapiens
Homo sapiens chromosome 20 clone RP4-749H19 map q13.11-13.33, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 20 clone RP4-749H19 map q13.11-13.33, ***SEQUENCING IN
Homo sapiens
Homo sapiens clone NH0169D01, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid F56H9, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans cosmid F56H9, complete sequence.
Caenorhabditis elegans
Homo sapiens clone RP11-15D18, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Homo sapiens clone RP11-15D18, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Homo sapiens
Corynebacterium
glutamicum
Paralichthys olivaceus
Paralichthys olivaceus
Drosophila melanogaster chromosome 2 clone BACR04E05 (D1055) RPCI-98 04.E.5 map
Drosophilia
melanogaster
Drosophila melanogaster, chromosome 2R, region 57B1-57B6, P1 clone DS03659, complete
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04E05 (D1055) RPCI-98 04.E.5 map
Drosophila
melanogaster
Arabidopsis thaliana chromosome II BAC T27K22 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens clone NH0355I13, WORKING DRAFT SEQUENCE, 1 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens, clone hRPK.78_A_1, complete sequence.
Homo sapiens
Caenorhabditis elegans chromosome IV clone Y43C5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome IV clone Y43C5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Chironomus tentans mRNA for P23 protein (23 kDa).
Chironomus tentans
Chironomus tentans mRNA for hnRNP protein, hrp23.
Chironomus tentans
Arabidopsis thaliana
Lycopersicon esculentum
Lycopersicon esculentum
Lycopersicon esculentum
Homo sapiens chromosome 21q22.3, PAC clones 314N7, 225L15, BAC clone 7B7, complete
Homo sapiens
Homo sapiens chromosome 21q22.3, PAC clones 314N7, 225L15, BAC clone 7B7, complete
Homo sapiens
Homo sapiens
Homo sapiens chromosome 14 clone R-501E21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-501E21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
P. pseudoalcaligenes dioxygenase (bphABC) gene cluster, complete cds.
Pseudomonas
pseudoalcaligenes
Pseudomonas sp. LB400 biphenyl dioxygenase (bphA), biphenyl dioxygenase (bphE), biphenyl
Burkholderia sp. LB400
Pseudomonas aeruginosa
Homo sapiens clone NH0144P23, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens BAC clone NH0538D15 from 7q11.23-q21.1, complete sequence.
Homo sapiens
Homo sapiens clone NH0144P23, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid F01G12.
Caenorhabditis elegans
Homo sapiens chromosome 5, P1 clone 792C12 (LBNL H22), complete sequence.
Homo sapiens
Canis familiaris TTX-resistant sodium channel mRNA, complete cds.
Canis familiaris
Homo sapiens
Rhodobacter sphaeroides nitric oxide reductase operon; norC, norB, norQ, norD, nnrT and nnrU
Rhodobacter sphaeroides
Homo sapiens chromosome 12 clone 917O5, complete sequence.
Homo sapiens
Homo sapiens PAC clone DJ0170O19 from 7p15-p21, complete sequence.
Homo sapiens
Homo sapiens chromosome 17 clone cosmid 5L5 map p11, ***SEQUENCING IN
Homo sapiens
A. thaliana mitochondrial genome, part B.
Mitochondrion
Arabidopsis thaliana
Arabidopsis thaliana chromosome I BAC F28O16 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC T18C6 genomic sequence, complete sequence.
Arabidopsis thaliana
B. taurus (cos1E3) microsatellite DNA (362 bp).
Bos taurus
B. taurus (cos1E3) microsatellite DNA (362 bp).
Bos taurus
Arabidopsis thaliana kinesin-like heavy chain (KATD) mRNA, complete cds.
Arabidopsis thaliana
Arabidopsis thaliana BAC IG002P16.
Arabidopsis thaliana
Arabidopsis thaliana kinesin-like heavy chain (KATD) mRNA, complete cds.
Arabidopsis thaliana
Drosophila melanogaster chromosome 3 clone BACR05A08 (D750) RPCI-98 05.A.6 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR05A08 (D750) RPCI-98 05.A.8 map
Drosophila melanogaster
Homo sapiens PAC clone DJ044L15 from Xq23, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Thermomicrobium roseum 70 kDa heat shock protein Hsp70 (DnaK) gene, complete cds.
Thermomicrobium
roseum
Homo sapiens chromosome 20 clone RP4-791K14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP4-791K14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP11-298O6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP4-791K14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP4-791K14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Zea mays
Z. mays CPNA gene encoding mitochondrial chaperonin-60.
Zea mays
Z. mays mRNA for mitochondrial chaperonin hsp60.
Zea mays
Homo sapiens clone DJ0655N24, complete sequence.
Homo sapiens
Homo sapiens clone DJ0655N24, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.192_H_23, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.192_H_23, complete sequence.
Homo sapiens
Orgyia pseudotsugata nuclear polyhedrosis virus complete genome.
Orgyia pseudotsugata
Homo sapiens clone DJ0837C09, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0837C09, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Orgyia pseudotsugata nuclear polyhedrosis virus complete genome.
Orgyia pseudotsugata
Homo sapiens chromosome 17, Neurofibromatosis 1 locus, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens Chromosome 16 BAC clone CIT987SK-A-A-218C7, complete sequence.
Homo sapiens
Homo sapiens PAC 128M19 derived from chromosome 21q22.3, containing the HMG-14 and
Homo sapiens
Homo sapiens chromosome 17 clone 2286_H_12 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 8 clone PAC 87.2 map 8q24.1, complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_558D4. ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_558D4, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana BAC F21E10.
Arabidopsis thaliana
Homo sapiens DNA for immunoglobulin heavy-chain variable region, complete sequence,
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, Q78C10-149C3 region,
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.566_B_16, complete sequence.
Homo sapiens
Homo sapiens clone NH0418H16, ***SEQUENCING IN PROGRESS***, 6 unordered pieces.
Homo sapiens
Homo sapiens clone NH0418H16, ***SEQUENCING IN PROGRESS***, 6 unordered pieces.
Homo sapiens
Thermotoga maritima section 19 of 136 of the complete genome.
Thermotoga maritima
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 72/162.
Mycobacterium
tuberculosis
Mus musculus
Homo sapiens
Cytophaga sp. 16S rRNA gene, partial sequence.
Cytophaga sp.
Homo sapiens chromosome 8 clone 318_G_5 map 8, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens chromosome 8 clone 318_G_5 map 8, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens
Caenorhabditis elegans chromosome V clone Y94A7, ***SEQUENCING IN
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone Y94A7, ***SEQUENCING IN
Caenorhabditis elegans
Borrelia burgdorferi (section 68 of 70) of the complete genome.
Borrelia burgdorferi
Mus musculus chromosome 10 clone RP21-536F4 map 10, ***SEQUENCING IN
Mus musculus
Mus musculus mRNA for GANP protein.
Mus musculus
Homo sapiens chromosome 5 clone CITB-H1_2176I21, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana
Arabidopsis thaliana
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Homo sapiens mRNA; cDNA DKFZp586O0118 (from clone DKFZp586O0118).
Homo sapiens
Mus musculus
Mus musculus
Emericella nidulans
Homo sapiens chromosome 19, cosmid F24069, complete sequence.
Homo sapiens
Vicia faba ferredoxin NADP+ reductase precursor (fnr) mRNA, complete cds.
Vicia faba
Homo sapiens chromosome 19, cosmid F24069, complete sequence
Homo sapiens
Candida albicans strain 1161 agglutinin-like protein 6 (ALS6) gene, complete cds
Candida albicans
Juglans nigra × Juglans regia mRNA for chalcone synthase (CHS1)
Juglans nigra × Juglans
regia
Juglans nigra × Juglans regia mRNA for chalcone synthase (CHS2)
Juglans nigra × Juglans
regia
C. glutamicum putP gene
Corynebacterium
glutamicum
Anopheles gambiae prophenotoxidase mRNA, complete cds
Anopheles gambiae
Anopheles gambiae prophenotoxidase (AgProPO) gene, complete cds
Anopheles gambiae
C. glutamicum putP gene
Corynebacterium
glutamicum
Homo sapiens chromosome 1 clone RP1-120G22, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 1 clone RP1-120G22, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Florometra serratissima mitochondrion, complete genome
Mitochondrion
Florometra serratissima
C. elegans complete mitochondrial genome
Caenorhabditis elegans
Florometra serratissima mitochondrion, complete genome
Florometra serratissima
Homo sapiens
Drosophila melanogaster genome survey sequence SP6 end of BAC BACN04K17 of DrosBAC
Drosophila melanogaster
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Magnaporthe grisea
Magnaporthe grisea
B. taurus bmmp9 mRNA for matrix metalloproteinase
Bos taurus
Corynebacterium glutamicum gltB and gltD genes for glutamine 2-oxoglutarate aminotransferase
Corynebacterium
glutamicum
Drosophila melanogaster chromosome 2 clone BACR04I07 (D644) RPCI-98 04 I 7 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04I07 (D644) RPCI-98 04 I 7 map
Drosophila melanogaster
Mycobacterium smegmatis catalase-peroxidase (katG), putative arabinosyl transferase (embC,
Mycobacterium
smegmatis
Mycobacterium avium EmbR (embR), EmbA (embA) and EmbB (embB) genes, complete cds.
Mycobacterium avium
Mycobacterium tuberculosis H37Rv complete genome; segment 156/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome 9 duplication of the T cell receptor beta locus and trypsinogen gene
Homo sapiens
Homo sapiens chromosome 9 duplication of the T cell receptor beta locus and trypsinogen gene
Homo sapiens
Homo sapiens
Mus musculus zinc finger protein (Krox-24) gene, exon 2.
Mus musculus
Drosophila melanogaster chromosome 2 clone BACR37I09 (D593) RPCI-98 37.I.9 map
Drosophila melanogaster
Anabaena sp. PCC 7120 putative polyketide synthase gene, complete cds.
Anabaena sp.
Mus musculus D-dopachrome tautomerase gene, complete cds.
Mus musculus
Mus musculus D-dopachrome tautomerase gene, complete cds.
Mus musculus
Arabidopsis thaliana genomic DNA, chromosome 5, P1 clone: MHK7, complete sequence.
Arabidopsis thaliana
Mus musculus
Lycopersicon esculentum
Homo sapiens chromosome 19, CIT-HSP-146e8, complete sequence.
Homo sapiens
Homo sapiens chromosome 19, CIT-HSP-146e8, complete sequence.
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 45 unordered pieces.
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 45 unordered pieces.
Homo sapiens
Drosophila melanogaster genome survey sequence TET3 end of BAC # BACR11G02 of
Drosophila melanogaster
Streptomyces griseus AmfR, AmfA and AmfB genes and 4 ORFs, complete cds.
Streptomyces griseus
Homo sapiens clone NH0462A19, complete sequence.
Homo sapiens
Homo sapiens clone NH0399H17, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Mortierella alpina gene for cytochrome b5, complete cds.
Mortierella alpina
Homo sapiens
C. glutamicum DNA for promoter fragment F34.
Corynebacterium
glutamicum
Caenorhabditis elegans cosmid F56G4, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans cDNA clone yk491h3 5′, mRNA sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Paracoccidioides brasiliensis heat shock protein 70 (Hsp70) gene, complete cds.
Paracoccidioides
brasiliensis
Homo sapiens, ***SEQUENCING IN PROGRESS***, 2 ordered pieces.
Homo sapiens
Homo sapiens, complete sequence.
Homo sapiens
Paracoccidioides brasiliensis heat shock protein 70 (Hsp70) gene, complete cds.
Paracoccidioides
brasiliensis
Campylobacter jejuni major outer membrane porin gene, complete cds.
Campylobacter jejuni
Rattus norvegicus
C. glutamicum lysl gene for L-lysine permease.
Corynebacterium
glutamicum
Homo sapiens chromosome 17, clone hRPK.746_E_8, complete sequence.
Homo sapiens
C. glutamicum lysl gene for L-lysine permease.
Corynebacterium
glutamicum
C. glutamicum lysl gene for L-lysine permease.
Corynebacterium
glutamicum
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR17F05 (D977) RPCI-98 17.F.5
Drosophila melanogaster
Homo sapiens clone NH0064I02, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone NH0064I02, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Trypanosoma cruzi
Homo sapiens chromosome 17 clone hRPK.19_F_16 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17 clone hRPK.19_F_16 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17 clone hRPK.19_F_16 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, SLC5A3-f4A4 region,
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, segment 22/28, complete sequence.
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone
Homo sapiens
Homo sapiens BAC clone NH0436C12 from 2, complete sequence.
Homo sapiens
Homo sapiens chromosome 18, clone hRPK.474_N_24, complete sequence.
Homo sapiens
Homo sapiens chromosome 18, clone hRPK.474_N_24, complete sequence.
Homo sapiens
Homo sapiens
H. sapiens FGF/int-2 gene upstream flanking region.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 25/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 144/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 144/162.
Mycobacterium
tuberculosis
Homo sapiens Chromosome 12p13.3 BAC RPCI11-21K20 (Roswell Park Cancer Institute
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR49A06 (D772) RPCI-98 49.A.6 map
Drosophila melanogaster
Homo sapiens Chromosome 12p13.3 BAC RPCI11-21K20 (Roswell Park Cancer Institute
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1096J16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1096J16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Homo sapiens chromosome 6 clone RP1-202D23 map q14.1-15, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 6 clone RP1-202D23 map q14.1-15, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Leishmania major
Homo sapiens
Oryza sativa
Cryptosporidium pervum
Homo sapiens chromosome 17 clone 118_B_18 map 17, ***SEQUENCING IN
Homo sapiens
C. heterostrophus gene for trifunctional tryptophan synthase.
Cochliobolus
heterostrophus
Homo sapiens
Homo sapiens
Homo sapiens
C. glutamicum betP gene.
Corynebacterium
glutamicum
Homo sapiens
Drosophila melanogaster, chromosome 2R, region 59C1-59C5, P1 clones DS06621 and
Drosophila melanogaster
Homo sapiens clone 10_J_17, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 10_J_17, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_560O9, ***SEQUENCING IN
Homo sapiens
Oryza sativa
Homo sapiens, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
S. cerevisiae chromosome XIII cosmid 9952.
Saccharomyces
cerevisiae
Saccharomyces
cerevisiae
S. cerevisiae PSE-1 gene.
Saccharomyces
cerevisiae
Drosophila melanogaster chromosome 2 clone BACR01N17 (D1036) RPCI-98 01.N.17
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR01N17 (D1036) RPCI-98 01.N.17
Drosophila melanogaster
Homo sapiens chromosome 19 clone CIT-HSPC_251H24, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Rattus norvegicus beta-2 adrenergic receptor gene, complete cds and promoter region.
Rattus norvegicus
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Hordeum vulgare (clone ABG380) chromosome 4H, 6H, 7H STS mRNA, sequence tagged site.
Hordeum vulgare
Homo sapiens
Corynebacterium glutamicum biotin synthase (bioB) gene, complete cds.
Corynebacterium
glutamicum
Homo sapiens
Drosophila melanogaster chromosome 2 clone DS01630 (D506) map 60C7-60C8 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS04467 (D447) map 60C6-60C8 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS01630 (D506) map 60C7-60C8 strain y;
Drosphila melanogaster
Homo sapiens
N. gonorrhoeae pilC1 gene, strain 640.
Neisseria gonorrhoeae
N. gonorrhoeae pilC1 gene, strain 640.
Neisseria gonorrhoeae
Homo sapiens chromosome 16 clone 474B12, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 16 clone 474B12, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens
Corynebacterium diphtheriae heme oxygenase homolog (hmuO) gene, complete cds.
Corynebacterium
diphtheriae
Corynebacterium diphtheriae mRNA for Heme oxygenase, complete cds.
Corynebacterium
diphtheriae
Oryza sativa
Caenorhabditis elegans cosmid F22B3, complete sequence.
Caenorhabditis elegans
Corynebacterium glutamicum glnA gene.
Corynebacterium
glutamicum
Arabidopsis thaliana
Corynebacterium glutamicum glnA gene.
Corynebacterium
glutamicum
Corynebacterium glutamicum glnA gene.
Corynebacterium
glutamicum
X. faevis FIM-B.1 gene.
Xenopus laevis
Corynebacterium glutamicum glnA gene.
Corynebacterium
glutamicum
Corynebacterium glutamicum heat shock, ATP-binding protein (clpB) gene, complete cds.
Corynebacterium
glutamicum
Corynebacterium glutamicum dapD gene, complete CDS.
Corynebacterium
glutamicum
Drosophila melanogaster
Brevibacterium lactofermentum tryptophan operon.
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Orgyia pseudotsugata nuclear polyhedrosis virus complete genome.
Orgyia pseudotsugata
Orgyia pseudotsugata nuclear polyhedrosis virus complete genome.
Orgyia pseudotsugata
Drosophila melanogaster chromosome 2 clone BACR07J20 (D918) RPCI-98 07.J.20 map
Drosophila melanogaster
Danio rerio
Homo sapiens
Homo sapiens
Homo sapiens chromosome 16 clone LA16-312E8, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 16 clone LA16-312E8, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Bos taurus
Homo sapiens
Homo sapiens clone RG074A24, ***SEQUENCING IN PROGRESS***, 25 unordered pieces.
Homo sapiens
Homo sapiens clone RG074A24, ***SEQUENCING IN PROGRESS***, 25 unordered pieces.
Homo sapiens
Brevibacterium lactofermentum DNA for D-2-hydroxyisocaproate dehydrogenase (ddh),
Corynebacterium
glutamicum
Corynebacterium glutamicum ddh gene for meso-diaminopimelate D-dehydrogenase
Corynebacterium
glutamicum
Corynebacterium glutamicum ddh gene for meso-diaminopimelate D-dehydrogenase
Corynebacterium
glutamicum
Corynebacterium glutamicum ddh gene for meso-diaminopimelate D-dehydrogenase
Corynebacterium
glutamicum
Brevibacterium lactofermentum DNA for D-2-hydroxyisocaproate dehydrogenase (ddh),
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Homo sapiens chromosome 16 clone RPCI-11_184F14, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_184F14, ***SEQUENCING IN
Homo sapiens
Homo sapiens tight junction protein ZO-2 (TJP2) gene, exons 8 and 9.
Homo sapiens
Lotus japonicus
Neurospora crassa
Drosophila melanogaster DNA sequence (P1 DS00445 (D93)), complete sequence.
Drosophila melanogaster
Homo sapiens clone RP11-19D19, ***SEQUENCING IN PROGRESS***, 33 unordered pieces.
Homo sapiens
Homo sapiens clone RP11-19D19, ***SEQUENCING IN PROGRESS***, 33 unordered pieces.
Homo sapiens
C. burnetii heat shock operon encoding two heat shock proteins (htpA and htpB), complete cds.
Coxiella burnetii
C. barabensis (griseus) mRNA for glucose phosphate isomerase.
Cricetulus griseus
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 28/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y224.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B2168.
Mycobacterium leprae
Drosophila melanogaster nudel (ndl) mRNA, complete cds.
Drosophila melanogaster
Drosophila melanogaster nudel (ndl) mRNA, complete cds.
Drosophila melanogaster
Leishmania major chromosome 1, complete sequence.
Leishmania major
Mus musculus
Leishmania major chromosome 1, complete sequence.
Leishmania major
Oryza sativa
Homo sapiens
Oryza sativa
Homo sapiens
R. capsulatus complete photosynthesis gene cluster.
Rhodobacter capsulatus
Homo sapiens
Arabidopsis thaliana chromosome I BAC T26J12 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome I BAC T26J12 genomic sequence, complete sequence.
Arabidopsis thaliana
Hansenula wingei mitochondrial DNA, complete sequence.
Mitochondrion Pichia
canadensis
Hansenula wingei mitochondrial DNA, complete sequence.
Mitochondrion Pichia
canadensis
Homo sapiens chromosome 14 clone R-1033H12, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-1033H12, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-1033H12, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Caenorhabditis elegans cosmid C32B5.
Caenorhabditis elegans
Caenorhabditis elegans cosmid C32B5.
Caenorhabditis elegans
Homo sapiens chromosome 17, clone hRPK.167_N_20, complete sequence.
Homo sapiens
Homo sapiens SERCA3 gene, exons 11-14.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.167_N_20, complete sequence.
Homo sapiens
Homo sapiens SERCA3 gene, exons 11-14.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.167_N_20, complete sequence.
Homo sapiens
Homo sapiens
Pyrococcus horikoshii OT3 genomic DNA, 544001-777000 nt. position (3/7).
Pyrococcus horikoshii
Arabidopsis thaliana chromosome 1 BAC F25A4 sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens
Caenorhabditis elegans
elegans cDNA clone yk188a1 5′, mRNA sequence.
Caenorhabditis elegans
elegans cDNA clone yk506a5 5′, mRNA sequence.
Caenorhabditis elegans
elegans cDNA clone yk459h10 5′, mRNA sequence.
Mycobacterium tuberculosis H37Rv complete genome; segment 114/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 148/162.
Mycobacterium
tuberculosis
Homo sapiens
Aeropyrum pernix genomic DNA, section 6/7.
Aeropyrum pernix
L. donovani hsp100 gene.
Leishmania donovani
Oryza sativa
Aeropyrum pernix genomic DNA, section 6/7.
Aeropyrum pernix
Aeropyrum pernix genomic DNA, section 6/7.
Aeropyrum pernix
L. donovani hsp100 gene.
Leishmania donovani
Mus musculus
Homo sapiens clone 44_J_4, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Homo sapiens clone 44_J_4, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Myxococcus xanthus ATP-dependent protease proteolytic subunit ClpP (clpP), ATP-dependent
Myxococcus xanthus
Porphyra sp. DNA, internal transcribed spacer 1 (ITS1).
Porphyra sp.
Glycine max
Homo sapiens
Streptococcus thermophilus bacteriophage Sfi21, complete genome.
Streptococcus
thermophilus
Streptococcus thermophilus bacteriophage Sfi19, complete genome.
Streptococcus
thermophilus
Mycobacterium tuberculosis sequence from clone y126.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 156/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B971 DNA sequence.
Mycobacterium leprae
Homo sapiens genomic DNA, chromosome 8p11.2, senescence gene region, section 9/19,
Homo sapiens
Caenorhabditis elegans cosmid F29G9.
Caenorhabditis elegans
Mycobacterium tuberculosis sequence from clone y414a.
Mycobacterium
tuberculosis
Drosophila melanogaster
Drosophila melanogaster
Oryza sativa
D. melanogaster ovo gene required for female germ line development.
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster
Homo sapiens
Drosophila melanogaster adducin-like protein, complete cds.
Drosophila melanogaster
Drosophila melanogaster hu-li tai shao (hts) mRNA, complete cds.
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR01I06 (D1054) RPCI-98 01.I.6 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR01I06 (D1054) RPCI-98 01.I.6 map
Drosophila melanogaster
Streptomyces coelicolor cosmid E9.
Streptomyces coelicolor
Corynebacterium glutamicum homoserine O-acetyltransferase (metA) gene, complete cds.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.299_G_24, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.299_G_24, complete sequence.
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_477D3, ***SEQUENCING IN
Homo sapiens
Homo sapiens clone NH0499D05, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens clone NH0499D05, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens chromosome 2 clone 101B6 map 2p11, complete sequence.
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_246B18, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_246B18, ***SEQUENCING IN
Homo sapiens
Mus musculus DNA, 5′ flanking region of interleukin 12 receptor beta 1.
Mus musculus
Homo sapiens
Homo sapiens
Glycine max aspartokinase-homoserine dehydrogenase (AK-HSDH) gene, partial cds.
Glycine max
Mus musculus
Mus musculus
Homo sapiens
Caenorhabditis elegans cosmid M162, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans cosmid M162, complete sequence.
Caenorhabditis elegans
Homo sapiens BAC clone GS165L15 from 7p15, complete sequence.
Homo sapiens
Plasmodium falciparum chromosome 4 strain 3D7, ***SEQUENCING IN PROGRESS***, in
Plasmodium falciparum
Plasmodium falciparum chromosome 4 strain 3D7, ***SEQUENCING IN PROGRESS***, in
Plasmodium falciparum
Mus musculus
Mus musculus
Mus musculus
Mus sp. 129SV V3/V1b vasopressin receptor gene, exon 2 and complete cds.
Mus musculus
Homo sapiens
Homo sapiens
Homo sapiens
S. lincolnensis (7B-11) Lincomycin production genes.
Streptomyces lincolnensis
Arabidopsis thaliana
Caenorhabditis elegans chromosome I clone Y87G2, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Caenorhabditis elegans chromosome I clone Y87G2, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Caenorhabditis elegans chromosome I clone Y6B3, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Streptomyces coelicolor cosmid 6G4.
Streptomyces coelicolor
Mycobacterium leprae cosmid B1620.
Mycobacterium leprae
Mycobacterium leprae cosmid B229.
Mycobacterium leprae
Toscana Virus genomic RNA for RNA-dependent RNA polymerase.
Toscana virus
Drosophila melanogaster twisted gastrulation (tsg) and serine protease (gd) genes, complete cds.
Drosophila melanogaster
Drosophila melanogaster twisted gastrulation (tsg) and serine protease (gd) genes, complete cds.
Drosophila melanogaster
Mycobacterium tuberculosis H37Rv complete genome; segment 111/162.
Mycobacterium
tuberculosis
Homo sapiens
Pyricularia grisea
Homo sapiens
Homo sapiens chromosome 16 clone 480G7, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 16 clone 480G7, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens
Homo sapiens
C. glutamicum icd gene for monomeric isocitrate dehydrogenase.
Corynebacterium
glutamicum
C. glutamicum icd gene for monomeric isocitrate dehydrogenase.
Corynebacterium
glutamicum
Homo sapiens
C. glutamicum icd gene for monomeric isocitrate dehydrogenase.
Corynebacterium
glutamicum
Streptomyces coelicolor isocitrate dehydrogenase (idh) gene, idh-B allele, complete cds.
Streptomyces coelicolor
Azotobacter vinelandii icd gene for isocitrate dehydrogenase, complete cds.
Azotobacter vinelandii
Mycobacterium tuberculosis H37Rv complete genome; segment 103/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y219.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome, segment 3/262.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid H24.
Streptomyces coelicolor
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Saccharomyces cerevisiae C-1-tetrahydrofolate synthase (ADE3) gene, complete cds.
Saccharomyces
cerevisiae
C. glutamicum gene leuA for isopropylmalate synthase.
Corynebacterium
glutamicum
Corynebacterium flavum aspartokinase (ask), and aspartate-semialdehyde dehydrogenase (asd)
Corynebacterium
flavescens
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR11H16 (D932) RPCI-98 11.H.16 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR11H16 (D932) RPCI-98 11.H.16 map
Drosophila melanogaster
Mycobacterium tuberculosis sequence from clone y219.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 3/262.
Mycobacterium
tuberculosis
Mus musculus
Arabidopsis thaliana chromosome II BAC F9C22 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC F2H17 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC F9C22 genomic sequence, complete sequence.
Arabidopsis thaliana
Escherichia coli genomic DNA. (23.8-24.2 min).
Escherichia coli
E. coli K12 HtrB gene.
Escherichia coli
Escherichia coli K-12 MG1655 section 97 of 400 of the complete genome.
Escherichia coli
Chlamydomonas sp.
Aedes aegypti
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 39/162.
Mycobacterium
tuberculosis
B. ammoniagenes purF gene.
Corynebacterium
ammoniagenes
Saccharomyces carlsbergensis assimilatory sulfite reductase (MET10) gene, complete cds.
Saccharomyces
pastorianus
B. ammoniagenes FAS gene.
Corynebacterium
ammoniagenes
Mycobacterium tuberculosis H37Rv complete genome, segment 111/162.
Mycobacterium
tuberculosis
Mycobacterium bovis fatty acid synthase gene, complete cds.
Mycobacterium bovis
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_499B15, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_499B15, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens PAC clone DJ0872F07 from 7q31, complete sequence.
Homo sapiens
Citrullus lanatus
Zea mays
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens DNA sequence from clone 440B3 on chromosome 22q12.1-3 Contains a
Homo sapiens
Zinnia elegans cysteine proteinase mRNA, complete cds.
Zinnia elegans
Corynebacterium glutamicum 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase gene,
Corynebacterium
glutamicum
Homo sapiens chromosome 17, clone hRPK.601_N_13, complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR48E08 (D843) RPCI-98 48.E.8 map
Drosophila melanogaster
Corynebacterium glutamicum 3-deoxy-D-arabinoheptulosonate-7-phosphate synthase gene,
Corynebacterium
glutamicum
Homo sapiens BAC clone DJ1122F04 from 7q11.23-q21.2, complete sequence.
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 48/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B1740.
Mycobacterium leprae
Mycobacterium tuberculosis H37Rv complete genome; segment 48/162.
Mycobacterium
tuberculosis
Arabidopsis thaliana
Homo sapiens
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC F19F24 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens
Arabidopsis thaliana chromosome II P1 MSF3 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens chromosome 19, CIT-HSP-87m17 BAC clone, complete sequence.
Homo sapiens
Oryza sativa
N. magadii rRNA operon.
Natrialba magadii
Porphyromonas gingivalis strain W50 immunoreactive 51 kD antigen PG52 gene, complete cds.
Porphyromonas
gingivalis
Homo sapiens
Homo sapiens
Mus musculus
Mus musculus
Mus musculus
Drosophila melanogaster chromosome 3 clone BACR33F18 (D764) RPCI-98 33.F.18 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR33F18 (D764) RPCI-98 33.F.18 map
Drosophila melanogaster
Drosophila melanogaster clone BACR7C10.
Drosophila melanogaster
Sinorhizobium meliloti partial oxi1 and dehydrogenase genes, isolate lpu119.
Sinorhizobium meliloti
Homo sapiens Xp22-140-141 BAC GSHB-128G5 (Genome Systems Human BAC library)
Homo sapiens
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 24 unordered pieces.
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 24 unordered pieces.
Homo sapiens
Homo sapiens chromosome unknown clone NH0480A20, WORKING DRAFT SEQUENCE, in
Homo sapiens
Drosophila melanogaster DNA sequence (P1 DS07851 (D49)), complete sequence.
Drosophila melanogaster
Arabidopsis thaliana BAC T24G23 from chromosome IV near 21 cM, complete sequence.
Arabidopsis thaliana
Mycobacterium leprae cosmid B596.
Mycobacterium leprae
Mycobacterium tuberculosis H37Rv complete genome; segment 155/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid H66.
Streptomyces coelicolor
Homo sapiens
Panax ginseng OSCPNY1 mRNA for beta-Amyrin Synthase, complete cds.
Panax ginseng
Homo sapiens
Mus musculus
Homo sapiens chromosome 15 clone RP11-430B1 map 15q21, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 15 clone RP11-430B1 map 15q21, ***SEQUENCING IN
Homo sapiens
Brevibacterium flavum genes for 7,8-diaminopelargonic acid aminotransferase and dethiobiotin
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR20D10 (D667) RPCI-98 20.D.10 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR20D10 (D667) RPCI-98 20.D.10 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR01A18 (D669) RPCI-98 01.A.18 map
Drosophila melanogaster
Homo sapiens chromosome 11 clone B759H8 map 11q23, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone B759H8 map 11q23, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone B759H8 map 11q23, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Gallus gallus
Homo sapiens clone NH0123E16, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_453G23, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CIT-HSPC_453G23, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana
Homo sapiens PAC clone DJ1086D14, complete sequence.
Homo sapiens
Homo sapiens
sapiens genomic clone Plate = 4832 Col = 3 Row = I, genomic survey sequence
Homo sapiens clone NH0065L03, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens clone NH0065L03, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens
Rhodococcus sp. NO1-1 CprS and CprR genes, complete cds.
Rhodococcus sp. NO1-1
Homo sapiens chromosome 16, cosmid clone 2H2 (LANL), complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2259I14, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana chromosome I BAC F13O11 genomic sequence, complete sequence.
Arabidopsis thaliana
Mus musculus Fabpe gene.
Mus musculus
Arabidopsis thaliana chromosome I BAC F13O11 genomic sequence, complete sequence.
Arabidopsis thaliana
Mus musculus
Helicobacter pylori 26695 section 111 of 134 of the complete genome.
Helicobacter pylori 26695
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR04C20 (D1035) RPCI-98 04.C.20 map
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04C20 (D1035) RPCI-98 04.C.20 map
Drosophila melanogaster
Eremothecium gossypii
Caenorhabditis elegans chromosome II clone Y38F1, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome II clone Y38F1, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Homo sapiens DNA sequence from PAC 934G17 on chromosome 1p36.21. Contains the
Homo sapiens
Homo sapiens
Homo sapiens genomic DNA, 21q region, clone: 64E11X19, genomic survey sequence.
Homo sapiens
Trypanosoma simiae mini-exon DNA.
Trypanosoma simiae
Rattus norvegicus
Rattus norvegicus Sprague-Dawley transketolase mRNA, complete cds.
Rattus norvegicus
Rattus sp.
Schizosaccharomyces pombe ABC transporter (mam1) gene, complete cds.
Schizosaccharomyces
pombe
S. pombe chromosome II cosmid c25B2.
Schizosaccharomyces
pombe
S. pombe chromosome II cosmid c2G5.
Schizosaccharomyces
pombe
Rhodospirillum rubrum CO-induced hydrogenase operon (cooM, cooK, cooL, cooX, cooU,
Rhodospirillum rubrum
L. esculentum mRNA for THM27 protein.
Lycopersicon esculentum
Lycopersicon esculentum
Mus musculus
Mus musculus
C. aurantiacus reaction center genes 1 and 2.
Chloroflexus aurantiacus
Danio rerio
Danio rerio
Caenorhabditis elegans chromosome V clone Y43F8, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Oryza sativa
Bacillus subtilis phosphoribosylaminoimidazole-carboxamide formyltransferase (purH-J) gene,
Bacillus subtilis
Bacillus subtilis phosphoribosylaminoimidazole-carboxamide formyltransferase (purH-J) gene,
Bacillus subtilis
Homo sapiens chromosome 15 clone 8_C_22 map 15, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Cyclotella cryptica mRNA for fucoxanthin chlorophyll a/c binding protein, fcp12.
Cyclotella cryptica
Homo sapiens
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Haemophilus influenzae Rd section 2 of 163 of the complete genome.
Haemophilus influenzae
Homo sapiens
Haemophilus influenzae Rd section 2 of 163 of the complete genome.
Haemophilus influenzae
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_551/11, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_551/11, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 137/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid 7A1.
Streptomyces coelicolor
Bacillus subtilis genomic DNA from the spoVM region.
Bacillus subtilis
Enterococcus faecium genomic DNA fragment.
Enterococcus faecium
Bacillus subtilis DNA, 283 Kb region containing skin element.
Bacillus subtilis
Bacillus subtilis complete genome (section 13 of 21): from 2395261 to 2613730.
Bacillus subtilis
Streptomyces coelicolor cosmid 4H8.
Streptomyces coelicolor
Homo sapiens clone 1_B_18, ***SEQUENCING IN PROGRESS***, 20 unordered pieces.
Homo sapiens
Homo sapiens clone 1_B_18, ***SEQUENCING IN PROGRESS***, 20 unordered pieces.
Homo sapiens
Homo sapiens
C. glutamicum lysl gene for L-lysine permease.
Corynebacterium
glutamicum
C. glutamicum lysl gene for L-lysine permease.
Corynebacterium
glutamicum
Mycobacterium tuberculosis H37Rv complete genome; segment 47/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome 20 clone RP4-564F22, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP4-564F22, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Glycine max unknown mRNA.
Glycine max
Mus musculus
Mus musculus
Drosophila melanogaster chromosome 2 clone BACR44N04 (D545) RPCI-98 44.N.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR44N04 (D545) RPCI-98 44.N.4 map
Drosophila melanogaster
Arabidopsis thaliana BAC F17I23.
Arabidopsis thaliana
Caenorhabditis elegans cosmid C05C10, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans cosmid C05C10, complete sequence.
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR42I20 (D748) RPCI-98 42.I.20 map
Drosophila melanogaster
Drosophila melanogaster Camguk (cmg) mRNA, complete cds.
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR42I20 (D748) RPCI-98 42.I.20 map
Drosophila melanogaster
Homo sapiens chromosome 15 clone BAC 64K10 map 14q25, LOW-PASS SEQUENCE
Homo sapiens
Homo sapiens chromosome 15 clone BAC 64K10 map 14q25, LOW-PASS SEQUENCE
Homo sapiens
Homo sapiens
Homo sapiens clone NH0065E07, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens clone NH0065E07, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Mus musculus chromosome 11 clone 196_F_5 map 11, ***SEQUENCING IN
Mus musculus
Homo sapiens
E. histolytica extrachromosomal ribosomal DNA for DRA I repeat unit.
Entamoeba histolytica
E. histolytica extrachromosomal ribosomal DNA downstream of rRNA genes.
Entamoeba histolytica
Bacillus subtilis complete genome (section 3 of 21): from 402751 to 611850.
Bacillus subtilis
Bacillus subtilis genome sequence, 148 kb sequence of the region between 35 and 47 degree.
Bacillus subtilis
Homo sapiens clone DJ0912I13, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Homo sapiens chromosome 17, clone hCIT.58_E_17, complete sequence.
Homo sapiens
Homo sapiens chromosome 17 clone 303_E_14, ***SEQUENCING IN PROGRESS***, 20
Homo sapiens
Homo sapiens chromosome 17 clone 303_E_14, ***SEQUENCING IN PROGRESS***, 20
Homo sapiens
Arabidopsis thaliana BAC F5K24.
Arabidopsis thaliana
M. barkeri hdrE & hdrD genes, ORF1, ORF2, ORF3 & ORF4.
Methanosarcina barkeri
S. cerevisiae chromosome XIII cosmid 9920.
Saccharomyces cerevisiae
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens clone NH0153B21, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Streptomyces coelicolor cosmid 7B7.
Streptomyces coelicolor
Homo sapiens chromosome 6 clone RP3-473J16 map q25.3-26, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 6 clone RP3-473J16 map q25.3-26, ***SEQUENCING IN
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 40/162.
Mycobacterium
tuberculosis
Pseudomonas aeruginosa YafE (yafE), LeuB (leuB), Asd (asd), FimV (fimV), and HisT (hisT)
Pseudomonas aeruginosa
Mycobacterium tuberculosis H37Rv complete genome; segment 41/162.
Mycobacterium
tuberculosis
Drosophila melanogaster chromosome X clone BACR49A05 (D745) RPCI-98 49.A.5 map
Drosophila melanogaster
Drosophila melanogaster chromosome X clone BACR49A05 (D745) RPCI-98 49.A.5 map
Drosophila melanogaster
Agrobacterium tumefaciens chemotaxis operon, complete sequence.
Agrobacterium tumefaciens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 20 clone RP11-555E18, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 20 clone RP11-555E18, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Caenorhabitis elegans cosmid C03B1.
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Ustilago maydis ferrichrome siderophore peptide synthetase (sid2) gene, complete cds.
Ustilago maydis
Homo sapiens gene for kinesin-like protein, complete cds.
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_157D17, ***SEQUENCING IN
Homo sapiens
Drosophila melanogaster DNA sequence (P1 DS01523 (D34)), complete sequence.
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster dual specificity kinase DYRK2 mRNA, complete cds.
Drosophila melanogaster
Homo sapiens
Homo sapiens clone NH0469M07, complete sequence.
Homo sapiens
Homo sapiens clone NH0013J08, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Arabidopsis thaliana genome survey sequence SP6 end of BAC T6D17 of TAMU library from
Arabidopsis thaliana
Arabidopsis thaliana genomic DNA, chromosome 5, TAC clone: K21L13, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana genomic DNA, chromosome 5, TAC clone: K21L13, complete sequence.
Arabidopsis thaliana
Mycobacterium leprae cosmid B2548.
Mycobacterium leprae
Mycobacterium leprae cosmid L373.
Mycobacterium leprae
Saccharomyces cerevisiae chromosome V cosmids 9781, 8198, 9115, 9981, and lambda clones
Saccharomyces cerevisiae
Homo sapiens clone DJ0782K24, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0782K24, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens clone NH0536I18, complete sequence.
Homo sapiens
Brugia malayi
Mus musculus
Trypanosoma brucei
Zea mays KI domain interacting kinase 1 (KIK1) mRNA, complete cds.
Zea mays
Homo sapiens clone NH0576F01, complete sequence.
Homo sapiens
Homo sapiens chromosome X clone bWXD111, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Homo sapiens chromosome X clone bWXD111, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome X clone LL0XNC01-242F8, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens Xp22 BAC GS-594A7 (Genome Systems Human BAC library) contains Bmx
Homo sapiens
Mycobacterium leprae cosmid B2126.
Mycobacterium leprae
Mycobacterium leprae cosmid B2533.
Mycobacterium leprae
Mus musculus gene for prolyl oligopeptidase, exon 11, 12, 13, 14, 15 and complete cds.
Mus musculus
Homo sapiens
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_468K18, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans cosmid M04G7.
Caenorhabditis elegans
Rattus sp.
Homo sapiens chromosome 8 clone BAC 393A07 map 8q, ***SEQUENCING IN
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR01A03 (D538) RPCI-98 01.A.3 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR01A03 (D538) RPCI-98 01.A.3 map
Drosophila melanogaster
Saccharomyces cerevisiae chromosome VIII cosmid 8179.
Saccharomyces cerevisiae
C. glutamicum ORF4 gene.
Corynebacterium
glutamicum
Streptomyces coelicolor cosmid 9A10.
Streptomyces coelicolor
Streptomyces toyocaensis D-ala-D-ala dipeptidase (vanXst) gene, complete cds; and unknown
Streptomyces toyocaensis
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Populus balsamifera
Mycobacterium tuberculosis H37Rv complete genome; segment 73/162.
Mycobacterium
tuberculosis
Mus musculus
Drosophila melanogaster chromosome 2 clone BACR02G15 (D643) RPCI-98 02.G.15 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR17E16 (D642) RPCI-98 17.E.16 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR02G15 (D643) RPCI-98 02.G.15 map
Drosophila melanogaster
Mus musculus
Oryza sativa
Mus musculus
Homo sapiens chromosome unknown clone NH0508H21, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0508H21, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0508H21, WORKING DRAFT SEQUENCE, in
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome, segment 69/162.
Mycobacterium
tuberculosis
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 104/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B1937.
Mycobacterium leprae
Homo sapiens, complete sequence.
Homo sapiens
H. vulgare gene encoding serine carboxypeptidase II, CP-MII.
Hordeum vulgare
Homo sapiens
Homo sapiens
Homo sapiens clone NH0490M08, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Homo sapiens clone NH0490M08, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Homo sapiens
Mus musculus, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Mus musculus
Drosophila melanogaster chromosome X clone BACN05G06 (D1107) RPCI-98 05.G.6 map
Drosophila melanogaster
Drosophila melanogaster chromosome X clone BACR08K05 (D885) RPCI-98 08.K.5 map
Drosophila melanogaster
Homo sapiens
Cryptosporidium parvum
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1118M15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1057B20 map q11.21-12, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1118M15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Drosophila melanogaster
melanogaster cDNA clone SD09973 5 prime, mRNA sequence.
Drosophila melanogaster DNA sequence (P1 DS07134 (D192)), complete sequence.
Drosophila melanogaster
Arabidopsis thaliana
Synechocystis sp. PCC6803 complete genome, 19/27, 2392729-2538999.
Synechocystis sp.
Caenorhabditis elegans chromosome III clone Y39E4, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome III clone Y39E4, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Sus scrofa beta-myosin heavy chain mRNA, complete cds.
Sus scrofa
Homo sapiens
Sus scrofa beta-myosin heavy chain mRNA, complete cds.
Sus scrofa
Mycobacterium tuberculosis H37Rv complete genome; segment 116/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B1177.
Mycobacterium leprae
Rattus sp.
Homo sapiens 12p11-37.2-54.4 BAC RP11-1060J15 (Roswell Park Cancer Institute Human
Homo sapiens
Homo sapiens
Homo sapiens chromosome Y, clone 264, M, 20, complete sequence.
Homo sapiens
Magnaporthe grisea
Magnaporthe grisea
Homo sapiens DNA sequence from PAC 179N16 on chromosome 6p21.1-21.33. Contains the
Homo sapiens
Bombyx mori
Bombyx mori
Sphingomonas aromaticivorans plasmid pNL1, complete plasmid sequence.
Sphingomonas
aromaticivorans
Drosophila melanogaster chromosome 2 clone BACR31D05 (D861) RPCI-98 31.D.5 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR31D05 (D861) RPCI-98 31.D.5 map
Drosophila melanogaster
Mycobacterium tuberculosis H37Rv complete genome; segment 108/162.
Mycobacterium
tuberculosis
Homo sapiens
R. rattus FE65 gene for adaptor protein interacting with the beta-amyloid precursor protein
Rattus rattus
Hamster papovavirus complete genome.
Hamster papovavirus
Hampster Papovavirus (HapV) genome.
Hamster papovavirus
Methanobacterium thermoautotrophicum from bases 976801 to 992232 (section 84 of 148) of
Methanobacterium
thermoautotrophicum
C. glutamicum mtrA gene locus with 5-methyltryptophan resistance.
Corynebacterium
glutamicum
C. glutamicum sequence corresponding to mtrA locus.
Corynebacterium
glutamicum
Brevibacterium lactofermentum tryptophan operon.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Homo sapiens
Corynebacterium glutamicum hom-thrB genes for homoserine dehydrogenase and homoserine
Corynebacterium
glutamicum
B. lactofermentum thr A gene.
Corynebacterium
glutamicum
Corynebacterium glutamicum hom-thrB genes for homoserine dehydrogenase and homoserine
Corynebacterium
glutamicum
Brevibacterium lactofermentum thrB gene for homoserine kinase.
Corynebacterium
glutamicum
Corynebacterium glutamicum hom-thrB genes for homoserine dehydrogenase and homoserine
Corynebacterium
glutamicum
Drosophila melanogaster, chromosome 2R, region 39A3-39B1, P1 clones DS02919 and
Drosophila melanogaster
Homo sapiens
Homo sapiens clone UWGC:g5129s003 from 7q31, complete sequence.
Homo sapiens
Homo sapiens
Oryza sativa
Homo sapiens
Homo sapiens
Homo sapiens chromosome X clone RP6-24A17, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome X clone RP6-24A17, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid ZC328.
Caenorhabditis elegans
Caenorhabditis elegans cosmid ZC328.
Caenorhabditis elegans
Flavobacterium sp. plasmid pOAD2 DNA, whole sequence.
Flavobacterium sp.
Arabidopsis thaliana genome survey sequence SP6 end of BAC T6P9 of TAMU library from
Arabidopsis thaliana
Arabidopsis thaliana genome survey sequence SP6 end of BAC T1C4 of TAMU library from
Arabidopsis thaliana
Lycopersicon esculentum
Mycobacterium tuberculosis H37Rv complete genome; segment 147/162.
Mycobacterium
tuberculosis
Mycobacterium bovis ribosomal proteins IF-1 (InfA), L36 (rpmJ), S13 (rpsM) and S11 (rpsK)
Mycobacterium bovis
C. glutamicum DNA, attachment site bacteriophage Phi-16.
Corynebacterium
glutamicum
C. glutamicum DNA, attachment site bacteriophage Phi-16.
Corynebacterium
glutamicum
C. glutamicum DNA, attachment site bacteriophage Phi-16.
Corynebacterium
glutamicum
Streptomyces coelicolor strain A3(2) transposase (tnpA) and Fe-containing superoxide
Streptomyces coelicolor
Drosophila melanogaster chromosome 3 clone BACR02M06 (D1003) RPCI-98 02.M.6 map
Drosophila melanogaster
Mycoplasma genitallum section 40 of 51 of the complete genome.
Mycoplasma genitalium
Homo sapiens
Xenopus laevis Smad6 mRNA, partial cds.
Xenopus laevis
Homo sapiens chromosome 6 clone RP3-435K13 map q14.1-16.1, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 6 clone RP3-435K13 map q14.1-16.1, ***SEQUENCING IN
Homo sapiens
Rhodobacter capsulatus cosmids 143-147, complete sequence.
Rhodobacter capsulatus
Caenorhabditis briggsae beta tubulin (mec-7) gene, complete cds.
Caenorhabditis briggsae
Caenorhabditis elegans chromosome III clone Y1A5, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Caenorhabditis elegans chromosome III clone Y1A5, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens chromosome 17, clone hRPK.334_M_10, complete sequence.
Homo sapiens
Arabidopsis thaliana chromosome I BAC T6L1 genomic sequence, complete sequence.
Arabidopsis thaliana
Mus musculus MMTV integration locus, aromatase gene, 3′ UTR.
Mus musculus
Mus musculus
Mus musculus
Homo sapiens
Homo sapiens chromosome 20 clone RP4-794I6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP4-794I6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Arabidopsis thaliana DNA chromosome 3, BAC clone T29H11.
Arabidopsis thaliana
Arabidopsis thaliana DNA chromosome 3, BAC clone T29H11.
Arabidopsis thaliana
Mus musculus
Arabidopsis thaliana genome survey sequence SP6 end of BAC F11C22 of IGF library from
Arabidopsis thaliana
Magnaporthe grisea
Arabidopsis thaliana genome survey sequence SP6 end of BAC F11C22 of IGF library from
Arabidopsis thaliana
Homo sapiens clone DJ0647C14, ***SEQUENCING IN PROGRESS***, 21 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens clone DJ0054D12, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens PAC clone 267D11 from 12, complete sequence.
Homo sapiens
Homo sapiens clone DJ0054D12, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0647C14, ***SEQUENCING IN PROGRESS***, 21 unordered pieces.
Homo sapiens
Homo sapiens Chromosome 16 BAC clone CIT987SK-A-259H10, complete sequence.
Homo sapiens
Homo sapiens chromosome 6 clone RP3-500L14 map p23-24.3, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 6 clone RP3-500L14 map p23-24.3, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens, ***SEQUENCING IN PROGRESS***, 2 ordered pieces.
Homo sapiens
Homo sapiens genomic DNA, chromosome 22q11.2, BCRL2 region, clone KB1183D5.
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 47/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 47/162.
Mycobacterium
tuberculosis
Mus musculus
Bacteroides fragilis beta-glucosidase gene, complete cds.
Bacteroides fragilis
M. leprae genes rplL, rpoB, rpoC, end, rpsL, rpsG, efg, tuf, rpsJ, rplC for ribosomal protein L7,
Mycobacterium leprae
Bacteroides fragilis beta-glucosidase gene, complete cds.
Bacteroides fragilis
Homo sapiens clone RP11-95I16, ***SEQUENCING IN PROGRESS***, 17 unordered pieces.
Homo sapiens
Homo sapiens clone RP11-95116, ***SEQUENCING IN PROGRESS***, 17 unordered pieces.
Homo sapiens
Methanobacterium thermoautotrophicum from bases 1698671 to 1709269 (section 145 of 148)
Methanobacterium
thermoautotrophicum
Feline leukemia virus, subgroup A (FeLV-FAIDS), complete nucleotide sequence.
Feline leukemia virus
Felis catus endogenous FeLV proviral polyprotein (protease (PRO), reverse transcriptase (RT),
Felis catus
Caprine arthritis encephalitis virus, complete proviral genome.
Caprine arthritis-
encephalitis virus
Homo sapiens chromosome 5 clone CIT-HSPC_298N6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_298N6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_298N6, ***SEQUENCING IN
Homo sapiens
Brugia malayi
Brugia malayi
Oryza sativa
Arabidopsis thaliana
Chromobacterium violaceum violacein biosynthetic gene cluster (vioA, vio B, vio C, vio D),
Chromobacterium
violaceum
Homo sapiens
Homo sapiens
Haemophilus influenzae Rd section 24 of 163 of the complete genome.
Haemophilus influenzae
Mus musculus mRNA for type II phosphatidylinositolphosphate kinase-alpha, complete cds.
Mus musculus
Rattus norvegicus PIPK2 alpha mRNA for phosphatidylinositol 5-phosphate 4-kinase alpha,
Rattus norvegicus
Drosophila melanogaster chromosome 3 clone BACR48G05 (D475) RPCI-98 48.G.5 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR48G05 (D475) RPCI-98 48.G.5 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR17F04 (D988) RPCI-98 17.F.4 map
Drosophila melanogaster
Toxoplasma gondii
Toxoplasma gondii
Drosophila melanogaster chromosome X clone BACR13G13 (D894) RPCI-98 13.G.13 map
Drosophila melanogaster
Mus musculus
Homo sapiens
Homo sapiens
Pseudomonas aeruginosa 6-phosphogluconate dehydratase (edd) gene, and glyceraldehyde-3-
Pseudomonas aeruginosa
Corynebacterium glutamicum 3′ ppc gene, secG gene, amt gene, ocd gene and 5′ soxA gene
Corynebacterium
glutamicum
Mus musculus
Mus musculus
Mus musculus
Mus musculus
Homo sapiens clone NH0340F16, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone NH0340F16, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Mus musculus
R. capsulatus complete photosynthesis gene cluster.
Rhodobacter capsulatus
R. capsulatus complete photosynthesis gene cluster.
Rhodobacter capsulatus
Homo sapiens low-voltage activated calcium channel alpha 1H mRNA, complete cds.
Homo sapiens
Corynebacterium glutamicum putative glutaredoxin NrdH (nrdH), NrdI (nrdI), and ribo-
Corynebacterium
glutamicum
Homo sapiens histone deacetylase 3 gene, exons 11, 12, 13 and partial cds.
Homo sapiens
Homo sapiens histone deacetylase 3 (HDAC3) gene, complete cds.
Homo sapiens
Sorghum bicolor
Homo sapiens chromosome 6 clone RP11-27F12 map p22.3-24, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 6 clone RP11-27F12 map p22.3-24, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 12q seeders clone RP11-210L7, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 12q seeders clone RP11-210L7, ***SEQUENCING IN
Homo sapiens
Homo sapiens
E. coli relA gene encoding ATP:GTP 3′-pyrophosphotransferase, complete cds.
Escherichia coli
Escherichia coli K-12 genome; approximately 62 minute region.
Escherichia coli
Escherichia coli K-12 MG 1655 section 252 of 400 of the complete genome.
Escherichia coli
P. cryptogea X24 gene for cryptogein.
Phytophthora cryptogea
Homo sapiens
Mus musculus mRNA for 26S proteasome non-ATPase subunit.
Mus musculus
Drosophila melanogaster chromosome 3 clone BACR32N16 (D973) RPCI-98 32.N.16 map 86C-
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR32N16 (D973) RPCI-98 32.N.16 map 86C-
Drosophila melanogaster
Homo sapiens 12q24.2 BAC RPCI11-407A16 (Roswell Park Cancer Institute Human BAC
Homo sapiens
Homo sapiens
Mus musculus bcl-2 alpha gene, exon 2.
Mus musculus
Borrelia burgdorferi (section 51 of 70) of the complete genome.
Borrelia burgdorferi
Homo sapiens chromosome 20 clone RP5-1030M6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1030M6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens clone RG052H06, ***SEQUENCING IN PROGRESS***, 11 unordered pieces.
Homo sapiens
Homo sapiens
Mus musculus
Gracilariopsis tenuifrons internal transcribed spacer region of the ribosomal repeat, ITS1, 5.8S
Gracilariopsis tenuifrons
Anabaena variabilis rbpF gene for RNA binding protein, complete cds.
Anabaena variabilis
Bordetella pertussis toxin liberation operon.
Bordetella pertussis
Homo sapiens
Arabidopsis thaliana chromosome 1 BAC F11A17 sequence, complete sequence.
Arabidopsis thaliana
Trypanosoma cruzi
P. anserina complete mitochondrial genome.
Mitochondrion Podospora
anserina
Homo sapiens chromosome unknown clone NH0367B19, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0367B19, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0367B19, WORKING DRAFT SEQUENCE, in
Homo sapiens
Mus musculus
Mus musculus
C. glutamicum leuB gene.
Corynebacterium
glutamicum
Mycobacterium tuberculosis H37Rv complete genome, segment 132/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid 1C2.
Streptomyces coelicolor
C. glutamicum leuB gene.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 10/162.
Mycobacterium
tuberculosis
Leishmania major chromosome 4 clone L6852 strain Freidlin, ***SEQUENCING IN
Leishmania major
Leishmania major chromosome 4 clone L6852 strain Freidlin, ***SEQUENCING IN
Leishmania major
C. glutamicum leuB gene.
Corynebacterium
glutamicum
Homo sapiens BAC clone NH0454P05 from 2, complete sequence.
Homo sapiens
Homo sapiens clone NH0390E09, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Drosophila melanogaster chromosome 3L/75A1 clone RPCI98-44L18, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/75A1 clone RPCI98-44L18, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/75A1 clone RPCI98-44L18, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster, chromosome 2L, region 22A1-22A1, P1 clone DS03601, complete
Drosophila melanogaster
Drosophila melanogaster genome survey sequence TET3 end of BAC:BACR23A23 of RPCI-98
Drosophila melanogaster
Drosophila melanogaster, chromosome 2L, region 22A1-22A1, P1 clone DS03601, complete
Drosophila melanogaster
Homo sapiens
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***,
Plasmodium falciparum
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***,
Plasmodium falciparum
Mycobacterium tuberculosis H37Rv complete genome; segment 95/162.
Mycobacterium
tuberculosis
Mus musculus
Homo sapiens Wiskott-Aldrich syndrome protein interacting protein (WASPIP) mRNA,
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 95/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B2533.
Mycobacterium leprae
Mycobacterium leprae cosmid B2126.
Mycobacterium leprae
Mycobacterium tuberculosis H37Rv complete genome, segment 93/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B2126.
Mycobacterium leprae
Streptomyces coelicolor putative ferredoxin, ARC (arc), 20S proteasome beta-subunit precursor
Streptomyces coelicolor
Mycobacterium tuberculosis H37Rv complete genome; segment 93/162.
Mycobacterium
tuberculosis
R. erythropolis DNA, 20S proteasome structural genes region (3301 bp).
Rhodococcus erythropolis
Rhodococcus erythropolis ORF6(2), ORF7(2), proteasome beta-type subunit 2 (prcB(2)), and
Rhodococcus erythropolis
Rhodococcus erythropolis ORF6(2), ORF7(2), proteasome beta-type subunit 2 (prcB(2)), and
Rhodococcus erythropolis
Drosophila melanogaster chromosome 2 clone BACR33D17 (D945) RPCI-98 33.D.17 map
Drosophila melanogaster
Coturnix coturnix
Homo sapiens chromosome 5 clone CIT978SKB_35K5, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_35K5, ***SEQUENCING IN
Homo sapiens
Homo Sapiens Chromosome X clone bWXD691, complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR24G16 (D1051) RPCI-98 24.G.16 map
Drosophila melanogaster
Neisseria meningitidis PglB (pglB), PglC (pglC), PglD (pglD), and AvtA (avtA) genes,
Neisseria meningitidis
Drosophila melanogaster chromosome 2 clone BACR06M19 (D615) RPCI-98 06.M.19 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR06M19 (D615) RPCI-98 06.M.19 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR06M19 (D615) RPCI-98 06.M.19 map
Drosophila melanogaster
L. mesenteroides glucose-6-phosphate dehydrogenase gene, complete cds.
Leuconostoc
mesenteroides
Homo sapiens chromosome 8 clone BAC 2379L20 map 8q24, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 8 clone BAC 2379L20 map 8q24, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Glycine max
Homo sapiens
Drosophila melanogaster chromosome 2 clone DS00678 (D449) map 59D3-59D4 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS00678 (D449) map 59D3-59D4 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04G19 (D646) RPCI-98 04.G.19 map
Drosophila melanogaster
Homo sapiens mRNA for KIAA0624 protein, partial cds.
Homo sapiens
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR48M17 (D614) RPCI-98 48.M.17 map
Drosophila melanogaster
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR48M17 (D614) RPCI-98 48.M.17 map
Drosophila melanogaster
Homo sapiens
Mus musculus
Mus musculus somatostatin receptor subtype 5 (sst5) gene, complete cds.
Mus musculus
Caenorhabditis elegans chromosome V clone Y51A2, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans cosmid Y51A2D, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone Y51A2, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Mycobacterium tuberculosis H37Rv complete genome; segment 97/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B1551 DNA sequence.
Mycobacterium leprae
Mycobacterium leprae cosmid B1554 DNA sequence.
Mycobacterium leprae
Homo sapiens chromosome 19, cosmid F18718, complete sequence.
Homo sapiens
Homo sapiens chromosome 19, cosmid F18718, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens chromosome 1 clone GS1-248A21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 1 clone GS1-248A21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 5, P1 clone 565a12 (LBNL H23), complete sequence.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 126/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid 6A9.
Streptomyces coelicolor
Aquifex aeolicus section 21 of 109 of the complete genome.
Aquifex aeolicus
Homo sapiens
Homo sapiens genomic DNA, 21q region, clone: B125C11 SpN045(-21), genomic survey sequence.
Homo sapiens
Homo sapiens
Homo sapiens tetraspan (NAG-2) mRNA, complete cds.
Homo sapiens
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis sequence from clone y151.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 59/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y151.
Mycobacterium
tuberculosis
Homo sapiens
Homo sapiens
Homo sapiens chromosome 10 clone RPCI11-587C2, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 10 clone RPCI11-587C2, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Caenorhabditis elegans chromosome V clone Y44A6, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone R08A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone R08A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone R08A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
S. pombe chromosome II cosmid c8D2.
Schizosaccharomyces
pombe
Schizosaccharomyces pombe 39 kb genomic DNA, clone c568.
Schizosaccharomyces
pombe
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 191 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
Streptomyces coelicolor cosmid H24.
Streptomyces coelicolor
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Gallus gallus NK class homeodomain transcription factor NKX3.2 mRNA, complete cds.
Gallus gallus
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster
Oryza sativa
Homo sapiens Human 12p11-37.2-54.4 BAC RPCI11-12D15 (Roswell Park Cancer Institute
Homo sapiens
Homo sapiens Human 12p11-37.2-54.4 BAC RPCI11-12D15 (Roswell Park Cancer Institute
Homo sapiens
Homo sapiens genomic DNA, 21q region, clone: 31C6X11, genomic survey sequence.
Homo sapiens
Homo sapiens genomic DNA, 21q region, clone: 31C6X11, genomic survey sequence.
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR03J04 (D687) RPCI-98 03.J.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR03J04 (D687) RPCI-98 03.J.4 map
Drosophila melanogaster
Homo sapiens clone NH0423F09, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Trypanosoma brucei
rhodesiense
Trypanosoma brucei
rhodesiense
Mus musculus clone UWGC: magap from 14D1-D2 (T-cell Receptor Alpha Locus), complete
Mus musculus
Mus musculus
Homo sapiens chromosome 17 clone 550_K_23 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.142_H_19, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.142_H_19, complete sequence.
Homo sapiens
Caenorhabditis elegans chromosome I clone Y71A12, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Homo sapiens clone 2_G_17, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Homo sapiens clone 2_G_17, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Homo sapiens clone 2_G_17, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Homo sapiens BAC clone 393I22 from 8q21, complete sequence.
Homo sapiens
Mycoplasma pulmonis FtsZ (ftsZ) gene, complete cds, methionyl-tRNA synthetase (metG) gene,
Mycoplasma pulmonis
Onchocerca volvulus
Onchocerca volvulus cDNA clone SWOv3MCAM09A04 5′, mRNA sequence.
Homo sapiens clone NH0230E20, ***SEQUENCING IN PROGRESS***, 65 unordered pieces.
Homo sapiens
Homo sapiens clone NH0230E20, ***SEQUENCING IN PROGRESS***, 65 unordered pieces.
Homo sapiens
Homo sapiens clone NH0230E20, ***SEQUENCING IN PROGRESS***, 65 unordered pieces.
Homo sapiens
Methanococcus jannaschii section 91 of 150 of the complete genome.
Methanococcus jannaschii
Homo sapiens
Morone saxatilis homeodomain protein Hox-A10 (Hoxa10), homeodomain protein Hox-A9
Morone saxatilis
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Oryctolagus cuniculus
Homo sapiens chromosome 10 clone CIT987SK-1144G6 map 10q25.1, complete sequence.
Homo sapiens
Rattus norvegicus
Drosophila melanogaster chromosome 3L/79D4 clone RPCI98-48E10, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/79D4 clone RPCI98-48E10, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/79D4 clone RPCI98-48E10, ***SEQUENCING IN
Drosophila melanogaster
Homo sapiens
F. rubripes GSS sequence, clone 165E10aE1, genomic survey sequence.
Fugu rubripes
Homo sapiens
Arabidopsis thaliana chromosome I BAC F23H11 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana
Arabidopsis thaliana chromosome I BAC F23H11 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens clone RPCI11-1028N23, ***SEQUENCING IN PROGRESS***, 47 unordered
Homo sapiens
Homo sapiens clone RPCI11-1028N23, ***SEQUENCING IN PROGRESS***, 47 unordered
Homo sapiens
Drosophila melanogaster DNA sequence (P1 DS05969 (D229)), complete sequence.
Drosophila melanogaster
Homo sapiens clone DJ1098J04, complete sequence.
Homo sapiens
Homo sapiens
Bacteroides fragilis NAD(H) glutamate dehydrogenase (gdhB) gene, complete cds.
Bacteroides fragilis
Homo sapiens chromosome 3, clone hRPK.44_A_1, complete sequence.
Homo sapiens
Homo sapiens 3q26.2-27 BAC RPCI11-408H1 (Roswell Park Cancer Institute Human BAC
Homo sapiens
Homo sapiens
Caenorhabditis elegans clone Y47D7, ***SEQUENCING IN PROGRESS***, 32 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone Y47D7, ***SEQUENCING IN PROGRESS***, 32 unordered pieces.
Caenorhabditis elegans
Giardia intestinalis
C. reinhardtii mRNA for 14-3-3 protein.
Chlamydomonas
reinhardtii
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_167P11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_167P11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_167P11, ***SEQUENCING IN
Homo sapiens
Neisseria meningitidis chloramphenicol acetyltransferase gene, complete cds.
Neisseria meningitidis
Oryza sativa
Plasmodium falciparum chromosome 13 strain 3D7, ***SEQUENCING IN PROGRESS***, in
Plasmodium falciparum
Homo sapiens clone NH0118E09, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Homo sapiens clone NH0118E09, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Homo sapiens clone NH0118E09, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Methanococcus jannaschii section 102 of 150 of the complete genome.
Methanococcus jannaschii
Methanococcus jannaschii section 102 of 150 of the complete genome.
Methanococcus jannaschii
Mycobacterium tuberculosis H37Rv complete genome; segment 24/162.
Mycobacterium
tuberculosis
Caenorhabditis elegans cosmid C41A3.
Caenorhabditis elegans
Homo sapiens clone NH0118M12, ***SEQUENCING IN PROGRESS***, 19 unordered pieces.
Homo sapiens
Prevotella albensis ftsQ (partial), ftsA and ftsZ genes and ORF-fts (partial).
Prevotella albensis
Prevotella albensis ftsQ (partial), ftsA and ftsZ genes and ORF-fts (partial).
Prevotella albensis
Homo sapiens chromosome 11 clone 1118i22 map q13, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 11 clone 1118i22 map q13, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.131_K_5, complete sequence.
Homo sapiens
Corynebacterium glutamicum heat shock, ATP-binding protein (clpB) gene, complete cds.
Corynebacterium
glutamicum
Bos taurus
Bos taurus
Aeropyrum pernix genomic DNA, section 7/7.
Aeropyrum pernix
Aeropyrum pernix genomic DNA, section 7/7.
Aeropyrum pernix
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.3-ter, Ter region, clone f27E1-T1136,
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.3-ter, Ter region, clone f27E1-T1136,
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.3-ter, Ter region, clone:T1957, complete
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens clone NH0498O20, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Homo sapiens clone NH0498O20, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Z. mays mRNA for b-32 protein, putative regulatory factor of zein expression (clone b-32.120).
Zea mays
Caenorhabditis elegans cosmid K10G6.
Caenorhabditis elegans
Caenorhabditis elegans cosmid K10G6.
Caenorhabditis elegans
Mycobacterium tuberculosis H37Rv complete genome; segment 126/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B250.
Mycobacterium leprae
Streptomyces lividans rpsP, trmD, rplS, sipW, sipX, sipY, sipZ, mutT genes and 4 open reading
Streptomyces lividans
Vibrio cholerae non-O1 gene for N-acetylglucosamine 6-phosphate deacetylase, NagC, NagE,
Vibrio cholerae non-O1
Homo sapiens PAC clone DJ1066K24 from 7p15, complete sequence.
Homo sapiens
Homo sapiens
Zea mays
Zea mays
Homo sapiens chromosome 5 clone CIT-HSPC_229P9, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Anopheles gambiae serine protease 14D mRNA, complete cds.
Anopheles gambiae
Homo sapiens
Anopheles gambiae serine protease 14D mRNA, complete cds.
Anopheles gambiae
Lycopersicon esculentum
Homo sapiens
Lycopersicon esculentum
Homo sapiens clone 14_K_21, ***SEQUENCING IN PROGRESS***, 8 unordered pieces.
Homo sapiens
Homo sapiens clone 14_K_21, ***SEQUENCING IN PROGRESS***, 8 unordered pieces.
Homo sapiens
Drosophila melanogaster clone BACR42I17.
Drosophila melanogaster
Drosophila melanogaster, chromosome 2R, region 58D4-58E2, BAC clone BACR48M13,
Drosophila melanogaster
Drosophila melanogaster, chromosome 2R, region 59E3-59F4, BAC clone BACR48M01,
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/70C1 clone RPCI98-2M20, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/70C1 clone RPCI98-2M20, ***SEQUENCING IN
Drosophila melanogaster
Homo sapiens clone 114_O_12, LOW-PASS SEQUENCE SAMPLING
Homo sapiens
Streptomyces coelicolor cosmid 5F2A.
Streptomyces coelicolor
B. pertussis tex gene.
Bordetella pertussis
Streptomyces coelicolor cosmid 5F2A.
Streptomyces coelicolor
Homo sapiens
Homo sapiens
Corynebacterium glutamicum ilvD gene.
Corynebacterium
glutamicum
Homo sapiens, clone hRPK.15_A_1, complete sequence.
Homo sapiens
Arabidopsis thaliana DNA chromosome 4, BAC clone F24G24 (ESSA project).
Arabidopsis thaliana
Homo sapiens chromosome 10 clone LA10NC01_15_E_11 map 10q26.3, ***SEQUENCING
Homo sapiens
Homo sapiens chromosome 10 clone LA10NC01_15_E_11 map 10q26.3, ***SEQUENCING
Homo sapiens
Homo sapiens chromosome 10 clone LA10NC01_15_E_11 map 10q26.3, ***SEQUENCING
Homo sapiens
Aquifex aeolicus section 107 of 109 of the complete genome.
Aquifex aeolicus
Neurospora crassa
Neurospora crassa
Aquifex aeolicus section 107 of 109 of the complete genome.
Aquifex aeolicus
B. subtilis prs, tms, and ctc (partial) genes for PRPP synthetase and two undefined gene
Bacillus subtilis
Homo sapiens
Homo sapiens
Thiobacillus ferrooxidans nitrogen metabolism regulator (ntrA) gene, complete cds.
Thiobacillus ferrooxidans
N. pharaonis sdhC, sdhD, sdhB and sdhA genes.
Natronomonas pharaonis
Homo sapiens chromosome 3p21.3 clone RPCI11-491D6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 3p21.3 clone RPCI11-491D6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome unknown clone NH0067G07, WORKING DRAFT SEQUENCE, in
Homo sapiens
Corynebacterium glutamicum amtP, glnB, glnD genes and partial ftsY and srp genes.
Corynebacterium
glutamicum
Drosophila melanogaster chromosome 3L/72A4 clone RPCI98-25O1, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/72A4 clone RPCI98-25O1, ***SEQUENCING IN
Drosophila melanogaster
Streptomyces coelicolor cosmid 6E10.
Streptomyces coelicolor
Magnaporthe grisea
Streptomyces coelicolor cosmid 6E10.
Streptomyces coelicolor
Oryza sativa subsp. indica Retrosat 1 retrotransposon and Ty3-Gypsy type Retrosat 2
Oryza sativa subsp. indica
Homo sapiens
Homo sapiens
Mus musculus, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Mus musculus
Homo sapiens chromosome 17, clone hCIT.162_E_12, complete sequence.
Homo sapiens
Mus musculus, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Mus musculus
Ambystoma tigrinum red cone visual pigment mRNA, complete cds.
Ambystoma tigrinum
M. leprae genomic dna sequence, cosmid b577.
Mycobacterium leprae
Homo sapiens chromosome 17, clone hRPC867C24, complete sequence.
Homo sapiens
S. cerevisiae chromosome IX sequence derived from lambda clones 5610-5004.
Saccharomyces cerevisiae
S. cerevisiae ribonucleotide reductase DNA damage-inducible regulatory subunit (DIN1) gene,
Saccharomyces cerevisiae
Trypanosoma brucei
rhodesiense
S. cerevisiae chromosome IV cosmid 8419.
Saccharomyces cerevisiae
S. cerevisiae PRP28 gene.
Saccharomyces cerevisiae
B. subtilis bacillopeptidase F (bpr) gene, complete cds.
Bacillus subtilis
Dictyostelium discoideum
Homo sapiens
Homo sapiens
Homo sapiens 12p13.3 BAC RPCI11-476M19 (Roswell Park Cancer Institute Human BAC
Homo sapiens
Homo sapiens chromosome 14 BAC containing gene for KIAA0759 and other possible new
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR03M22 (D1000) RPCI-98 03.M.22 map
Drosophila melanogaster
Homo sapiens
Homo sapiens
Homo sapiens
C. albicans cosmid Ca49C10.
Candida albicans
Arabidopsis thaliana
C. albicans cosmid Ca49C10.
Candida albicans
Corynebacterium glutamicum N-acetylglutamylphosphate reductase (argC), ornithine
Corynebacterium
glutamicum
C. glutamicum argC, argJ, argB, argD, and argF genes.
Corynebacterium
glutamicum
Corynebacterium glutamicum N-acetylglutamylphosphate reductase (argC), ornithine
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Mus musculus
Mus musculus
Mus musculus
Mus musculus
Mus musculus
Homo sapiens chromosome 19, BAC 41855 (CIT-B-32o4), complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hCIT.457_L_16, complete sequence.
Homo sapiens
Fugu rubripes prohormone convertase PACE4 (PACE4) gene, partial cds; and 1-
Fugu rubripes
Zea mays retrotransposon Cinful prpol mRNA, partial cds.
Zea mays
Caenorhabditis elegans
elegans cDNA clone yk566e10 5′, mRNA sequence.
Mus musculus
Corynebacterium glutamicum fda gene for fructose-bisphosphate aldolase (EC 4.1.2.13).
Corynebacterium
glutamicum
Emericella nidulans acid trehalase precursor (treA) gene, complete cds.
Emericella nidulans
Corynebacterium glutamicum fda gene for fructose-bisphosphate aldolase (EC 4.1.2.13).
Corynebacterium
glutamicum
Mycobacterium tuberculosis H37Rv complete genome; segment 48/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B1222.
Mycobacterium leprae
Streptomyces lavendulae
Homo sapiens
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***, 9
Plasmodium falciparum
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***, 9
Plasmodium falciparum
Homo sapiens clone 2_I_22, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 2_I_22, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 2_I_22, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_36O1, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_36O1, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans cosmid T05A8.
Caenorhabditis elegans
Homo sapiens chromosome 5 clone CIT978SKB_148I14, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_148I14, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_148I14, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens chromosome 16 clone LA16-439A6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 16 clone LA16-439A6, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Homo sapiens
Tetrahymena thermophila dynein heavy chain (DYH10) gene, partial cds.
Tetrahymena thermophila
Arabidopsis thaliana DNA chromosome 4, BAC clone F3L17 (ESSA project).
Arabidopsis thaliana
Arabidopsis thaliana DNA chromosome 4, BAC clone F3L17 (ESSA project).
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Catharanthus roseus G-box binding protein 1 (GBF1) mRNA, complete cds.
Catharanthus roseus
Arabidopsis thaliana
Homo sapiens clone NH0324G03, ***SEQUENCING IN PROGRESS***, 6 unordered pieces.
Homo sapiens
Homo sapiens clone NH0324G03, ***SEQUENCING IN PROGRESS***, 6 unordered pieces.
Homo sapiens
Homo sapiens DNA sequence from P1 p373c6 on chromosome 6p21.31-21.33. Contains zinc
Homo sapiens
Homo sapiens
Arabidopsis thaliana chromosome II BAC T6B13 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana genomic DNA, chromosome 3, TAC clone: K1G2, complete sequence.
Arabidopsis thaliana
Homo sapiens clone 44_C_14, ***SEQUENCING IN PROGRESS***, 12 unordered pieces.
Homo sapiens
Homo sapiens clone 44_C_14, ***SEQUENCING IN PROGRESS***, 12 unordered pieces.
Homo sapiens
Chlamydomonas sp. mRNA for alternative oxidase, partial cds.
Chlamydomonas sp.
Chlamydomonas sp. mRNA for alternative oxidase, partial cds.
Chlamydomonas sp.
Homo sapiens chromosome X clone RP1-136J15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome X clone RP1-136J15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR07M03 (D607) RPCI-98 07.M.3 map
Drosophila melanogaster
Homo sapiens chromosome 21q22.3 BAC 28F9, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens chromosome 21q22.3 BAC 28F9, complete sequence.
Homo sapiens
Caenorhabditis elegans cosmid Y50E8A, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans cosmid Y50E8A, complete sequence.
Caenorhabditis elegans
Arabidopsis thaliana genomic DNA, chromosome 5, BAC clone:F16F17, complete sequence.
Arabidopsis thaliana
C. glutamicum DNA for promoter fragment F10.
Corynebacterium
glutamicum
Mus musculus
Mus musculus
Mus musculus
Mus musculus
Zea mays
Homo sapiens chromosome 4 clone C0383J20 map 4p16, complete sequence.
Homo sapiens
Archaeoglobus fulgidus section 14 of 172 of the complete genome.
Archaeoglobus fulgidus
Homo sapiens chromosome 4 clone C0383J20 map 4p16, complete sequence.
Homo sapiens
Streptomyces coelicolor cosmid J1.
Streptomyces coelicolor
Mycobacterium tuberculosis H37Rv complete genome; segment 139/162.
Mycobacterium
tuberculosis
Pseudomonas aeruginosa PAO substrain OT684 pyoverdine gene transcriptional regulator PvdS
Pseudomonas aeruginosa
Homo sapiens BAC clone GS011E15 from 5q31, complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2340N2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2340N2, ***SEQUENCING IN
Homo sapiens
Bradyrhizobium japonicum aconitase (acnA) gene, complete cds.
Bradyrhizobium
japonicum
Mycobacterium tuberculosis H37Rv complete genome; segment 103/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 103/162.
Mycobacterium
tuberculosis
Rattus norvegicus mRNA for AIM-1, complete cds.
Rattus norvegicus
Rattus norvegicus mRNA for AIM-1, complete cds.
Rattus norvegicus
Drosophila melanogaster chromosome 3 clone BACR05C11 (D759) RPCI-98 05.C.11 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR05C11 (D759) RPCI-98 05.C.11 map
Drosophila melanogaster
Arabidopsis thaliana chromosome III BAC F7O18 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Caenorhabditis elegans chromosome V clone Y80D3, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Homo sapiens clone NH0549D18, ***SEQUENCING IN PROGRESS***, 30 unordered pieces.
Homo sapiens
Homo sapiens clone NH0549D18, ***SEQUENCING IN PROGRESS***, 30 unordered pieces.
Homo sapiens
Homo sapiens clone NH0549D18, ***SEQUENCING IN PROGRESS***, 30 unordered pieces.
Homo sapiens
C. glutamicum DNA for promoter fragment F10.
Corynebacterium
glutamicum
Homo sapiens clone 12_P_19, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 12_P_19, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Mus musculus
Mus musculus
Leishmania major
Escherichia coli K-12 chromosomal region from 67.4 to 76.0 minutes.
Escherichia coli
Escherichia coli K-12 chromosomal region from 67.4 to 76.0 minutes.
Escherichia coli
Escherichia coli K-12 MG1655 section 287 of 400 of the complete genome
Escherichia coli
Schistosoma mansoni
Caenorhabditis elegans chromosome I clone Y53C10, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome I clone Y53C10, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome I clone Y47H9, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Homo sapiens
Helicoverpa armigera mitochondrion D-loop, partial 12S rRNA gene, and partial tRNA-Met
Mitochondrion
Helicoverpa armigera
Homo sapiens
Bombyx mori
Mus musculus
Bombyx mori
Plasmodium vivax retyculocyte binding protein 1 gene, complete cds.
Plasmodium vivax
G. gallus mRNA for NeuroM protein.
Gallus gallus
Homo sapiens LON protease (LON) gene, nuclear gene encoding mitochondrial protein, exon 1.
Homo sapiens
Penaeus monodon
Homo sapiens
Homo sapiens clone hRPK.53_A_1, ***SEQUENCING IN PROGRESS***, 9 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.53_A_1, ***SEQUENCING IN PROGRESS***, 9 unordered pieces.
Homo sapiens
Homo sapiens chromosome 3 clone 78_O_24 map 3, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Rattus norvegicus
S. pombe chromosome II cosmid c19G7.
Schizosaccharomyces
pombe
Hordeum vulgare
Populus balsamifera
Arabidopsis thaliana chromosome I BAC T28P6 genomic sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome I BAC T28P6 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens chromosome 17, clone hRPK.118_F_13, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.118_F_13, complete sequence.
Homo sapiens
Homo sapiens chromosome 16 clone 344L6, ***SEQUENCING IN PROGRESS***, 85
Homo sapiens
Homo sapiens Chromosome 15q11-q13 PAC clone pDJ351h23 from the Prader-Will/Angelman
Homo sapiens
Homo sapiens BAC clone RG318M05 from 7q22-q31.1, complete sequence.
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 154/162.
Mycobacterium
tuberculosis
Aeromonas salmonicida chaperonin GroES and chaperonin GroEL genes, complete cds.
Aeromonas salmonicida
Mus musculus
Gallus gallus anonymous sequence from Cosmid mapping to chicken chromosome 3 (Cosmid
Gallus gallus
Gallus gallus anonymous sequence from Cosmid mapping to chicken chromosome 3 (Cosmid
Gallus gallus
Homo sapiens clone 82F9, complete sequence.
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.2, DSCR region, clone D47-S479, segment
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.2, DSCR region, clone D47-S479, segment
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens genomic DNA of 21q22.2 Down Syndrome region, segment 3/13.
Homo sapiens
Homo sapiens clone NH0005B09, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens clone NH0005B09, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Homo sapiens clone NH0350I24, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 76/162.
Mycobacterium
tuberculosis
M. tuberculosis TlyA gene.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid L247.
Mycobacterium leprae
Drosophila melanogaster chromosome 3 clone BACR27G04 (D985) RPCI-98 27.G.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR27G04 (D985) RPCI-98 27.G.4 map
Drosophila melanogaster
Caenorhabditis elegans clone Y65B4, ***SEQUENCING IN PROGRESS***, 6 unordered pieces.
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Drosophila melanogaster, chromosome 2L, region 23C1-23C5, P1 clones DS02190 and
Drosophila melanogaster
Danio rerio
Danio rerio
Homo sapiens
Lycopersicon esculentum
S. pombe chromosome I cosmid c3C7.
Schizosaccharomyces
pombe
S. pombe chromosome I cosmid c3C7.
Schizosaccharomyces
pombe
Homo sapiens chromosome 5 clone CIT978SKB_61G23, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_61G23, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone RPCI-PAC_241C15, ***SEQUENCING IN
Homo sapiens
Escherichia coli minutes 9 to 11 genomic sequence.
Escherichia coli
Escherichia coli minutes 9 to 11 genomic sequence.
Escherichia coli
E. coli genomic DNA, Kohara clone #356 (46.1-46.5 min.).
Escherichia coli
Homo sapiens chromosome 19, cosmid R31237, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens clone hRPK.96_A_1, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.96_A_1, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Escherichia coli K-12 chromosomal region from 92.8 to 00.1 minutes.
Escherichia coli
Escherichia coli K-12 MG1655 section 387 of 400 of the complete genome.
Escherichia coli
Escherichia coli leucine tRNA gene and ORF1 gene, complete cds.
Escherichia coli
Homo sapiens, complete sequence.
Homo sapiens
Homo sapiens Chromosome 22q11.2 PAC Clone p_n5 in BCRL2-GGT Region, complete
Homo sapiens
Synechocystis sp. PCC6803 complete genome, 24/27, 3002966-3138603.
Synechocystis sp.
Homo sapiens clone hRPK.68_A_1, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.68_A_1, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.68_A_1, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Thermotoga maritima section 128 of 136 of the complete genome.
Thermotoga maritima
Cavia cobaya mRNA for PH-20 protein.
Cavia porcellus
C. glutamicum proP gene.
Corynebacterium
glutamicum
Caenorhabditis elegans cosmid T06E6, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans clone Y9C9, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Caenorhabditis elegans
Homo sapiens PAC clone DJ0997N05 from 7q11.23-q21.1, complete sequence.
Homo sapiens
Homo sapiens clone NH0559J05, complete sequence.
Homo sapiens
Homo sapiens PAC clone DJ0997N05 from 7q11.23-q21.1, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.15_K_2, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.15_K_2, complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_575D19, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_575D19, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_575D19, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana chromosome III clone TAMU-T4P13, ***SEQUENCING IN
Arabidopsis thaliana
Arabidopsis thaliana chromosome III clone TAMU-T4P13, ***SEQUENCING IN
Arabidopsis thaliana
Arabidopsis thaliana chromosome III clone TAMU-T4P13, ***SEQUENCING IN
Arabidopsis thaliana
Homo sapiens
Homo sapiens clone 11_L_8, ***SEQUENCING IN PROGRESS***, 7 unordered pieces.
Homo sapiens
Homo sapiens clone 11_L_8, ***SEQUENCING IN PROGRESS***, 7 unordered pieces.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 161/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid 3C3.
Streptomyces coelicolor
Streptomyces coelicolor serine protease gene, complete cds.
Streptomyces coelicolor
Caenorhabditis elegans cosmid ZC101, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans
elegans cDNA clone yk432e11 5′, mRNA sequence.
Caenorhabditis elegans chromosome II clone Y54E2, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Mycobacterium tuberculosis H37Rv complete genome; segment 155/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B2407.
Mycobacterium leprae
M. leprae genomic dna sequence, cosmid b577.
Mycobacterium leprae
M. leprae genomic dna sequence, cosmid b577.
Mycobacterium leprae
Mycobacterium leprae cosmid B2407.
Mycobacterium leprae
Mycobacterium tuberculosis H37Rv complete genome; segment 155/162.
Mycobacterium
tuberculosis
Drosophila melanogaster genome survey sequence T7 end of BAC BACN05B20 of DrosBAC
Drosophila melanogaster
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 117/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid L581.
Mycobacterium leprae
Arabidopsis thaliana chromosome II BAC F16M14 genomic sequence, complete sequence.
Arabidopsis thaliana
Mycobacterium tuberculosis H37Rv complete genome; segment 137/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome, segment 4/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 137/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome 5 clone CIT978SKB_109F8, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_109F8, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_3P13, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans clone Y51H7, ***SEQUENCING IN PROGRESS***, 7 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y51H7, ***SEQUENCING IN PROGRESS***, 7 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y51H7, ***SEQUENCING IN PROGRESS***, 7 unordered
Caenorhabditis elegans
Corynebacterium glutamicum multidrug resistance protein (cmr) gene, complete cds.
Corynebacterium
glutamicum
Anoplodactylus portus 28S ribosomal RNA gene, partial sequence.
Anoplodactylus portus
Dictyostelium discoideum
Corynebacterium glutamicum unidentified sequence involved in histidine biosynthesis, partial
Corynebacterium
glutamicum
Drosophila melanogaster cosmid clone 86E4.
Drosophila melanogaster
Emericella nidulans abfB gene.
Emericella nidulans
Mycobacterium phage DS6A, Spe1/Nhel G fragment sequence.
Mycobacterium phage
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens clone NH0570F04, WORKING DRAFT SEQUENCE, 1 unordered pieces.
Homo sapiens
Homo sapiens clone NH0570F04, WORKING DRAFT SEQUENCE, 1 unordered pieces.
Homo sapiens
Mus musculus
Dictyostelium discoideum ubiquitin-conjugating enzyme protein UbcC (ubcC) mRNA,
Dictyostelium discoideum
Dictyostelium discoideum
Caenorhabditis elegans cosmid R03H10.
Caenorhabditis elegans
Arabidopsis thaliana
Homo sapiens
Arabidopsis thaliana DNA chromosome 4, BAC clone F6I18 (ESSA project).
Arabidopsis thaliana
Arabidopsis thaliana DNA chromosome 4, BAC clone F6I18 (ESSA project).
Arabidopsis thaliana
X. laevis mRNA for nuclear protein SDK2.
Xenopus laevis
Homo sapiens chromosome 18 clone 470_B_24 map 18, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 18 clone 470_B_24 map 18, ***SEQUENCING IN
Homo sapiens
Arabidopsis thaliana phytochelatin synthase 1 (AtPCS1) gene, complete cds.
Arabidopsis thaliana
Caenorhabditis elegans chromosome III clone Y48A6, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome III clone Y48A6, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome III clone Y48A6, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Mus musculus
Homo sapiens
P. diminuta iorA and iorB genes for isoquinoline 1-oxidoreductase.
Brevundimonas diminuta
Caenorhabditis elegans cosmid F46B6, complete sequence.
Caenorhabditis elegans
Homo sapiens
Homo sapiens clone FBF3 Crl-du-chat region mRNA.
Homo sapiens
Corynebacterium glutamicum DNA for L-Malate.quinone oxidoreductase.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens Chromosome 12p13.3 BAC RPCI11-21K20 (Roswell Park Cancer Institute
Homo sapiens
Mycobacterium leprae cosmid B1529 DNA sequence.
Mycobacterium leprae
Streptomyces coelicolor cosmid 6A5.
Streptomyces coelicolor
Mycobacterium tuberculosis H37Rv complete genome; segment 125/162.
Mycobacterium
tuberculosis
Helianthus annuus homeodomain protein 1 mRNA, complete cds.
Helianthus annuus
Helianthus annuus homeodomain protein 1 mRNA, complete cds.
Helianthus annuus
Pseudomonas chloroaphis polyurethanase esterase A (pueA) gene, complete cds.
Pseudomonas
chlororaphis
Pseudomonas chloroaphis polyurethanase esterase A (pueA) gene, complete cds.
Pseudomonas
chlororaphis
Corynebacterium glutamicum fda gene for fructose-bisphosphate aldolase (EC 4.1.2.13).
Corynebacterium
glutamicum
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC T06D20 genomic sequence, complete sequence.
Arabidopsis thaliana
Gallus gallus T-Box protein 4 (TBX4) mRNA, complete cds.
Gallus gallus
Homo sapiens
Homo sapiens
Homo sapiens
Xanthomonas oryzae
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 118/162.
Mycobacterium
tuberculosis
Streptomyces coelicolor cosmid 1B5.
Streptomyces coelicolor
M. leprae genomic dna sequence, cosmid b1912.
Mycobacterium leprae
Corynebacterium glutamicum beta C-S lyase (aecD) and branched-chain amino acid uptake
Corynebacterium
glutamicum
Drosophila melanogaster chromosome 3L/66B6 clone RPCI98-6E4, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/66B6 clone RPCI98-6E4, ***SEQUENCING IN
Drosophila melanogaster
Homo sapiens
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_323C21, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Caenorhabditis elegans clone F12E12, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone F12E12, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Homo sapiens chromosome 14 clone R-976B16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-976B16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens clone 10_L_13, ***SEQUENCING IN PROGRESS***, 14 unordered pieces.
Homo sapiens
Caenorhabditis elegans cosmid K04G11, complete sequence.
Caenorhabditis elegans
Homo sapiens clone DJ0042M02, ***SEQUENCING IN PROGRESS***, 13 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0042M02, ***SEQUENCING IN PROGRESS***, 13 unordered pieces.
Homo sapiens
Danio rerio
Caenorhabditis elegans chromosome X clone Y60A9, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome X clone Y60A9, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Magnaporthe grisea
Homo sapiens
Homo sapiens
Homo sapiens chromosome 11 clone RP11-85D24 map 11, WORKING DRAFT SEQUENCE,
Homo sapiens
Homo sapiens chromosome 11 clone RP11-85D24 map 11, WORKING DRAFT SEQUENCE,
Homo sapiens
Homo sapiens
Tolypocladium inflatum NRRL 28024 28S ribosomal RNA gene, partial sequence.
Tolypocladium inflatum
Mycobacterium leprae cosmid L458.
Mycobacterium leprae
Homo sapiens
S. cerevisiae fructose-1,6-bisphosphatase (FBP) gene, complete cds.
Saccharomyces cerevisiae
Saccharomyces cerevisiae chromosome XII cosmid 8039.
Saccharomyces cerevisiae
Caenorhabditis elegans cosmid F43C9.
Caenorhabditis elegans
Caenorhabditis elegans cosmid F43C9.
Caenorhabditis elegans
Mus musculus
Homo sapiens Chromosome 15q11-q13 PAC clone pDJ373b1 containing Angelman Syndrome
Homo sapiens
Homo sapiens
Homo sapiens Chromosome 15q11-q13 PAC clone pDJ373b1 containing Angelman Syndrome
Homo sapiens
Homo sapiens
Mus musculus
Caenorhabditis elegans cosmid C39D10
Caenorhabditis elegans
Caenorhabditis elegans cosmid F16H9, complete sequence
Caenorhabditis elegans
Caenorhabditis elegans cosmid CC4, complete sequence
Caenorhabditis elegans
Caenorhabditis elegans chromosome I clone Y26D4, ***SEQUENCING IN PROGRESS***, in
Caenorhabditis elegans
Drosophila melanogaster clone RPCI98-4O3, ***SEQUENCING IN PROGRESS***, 63
Drosophila melanogaster
Drosophila melanogaster clone RPCI98-4O3, ***SEQUENCING IN PROGRESS***, 63
Drosophila melanogaster
Caenorhabditis elegans
Strongylocentrotus purpuratus calcium-binding protein (endo16) mRNA, complete cds
Strongylocentrotus
purpuratus
Homo sapiens
Homo sapiens mRNA for KIAA0577 protein, complete cds.
Homo sapiens
C. glutamicum proP gene.
Corynebacterium
glutamicum
Lycopersicon esculentum
Caenorhabditis elegans cosmid T11F9, complete sequence
Caenorhabditis elegans
Homo sapiens chromosome 10 clone LA10NC01_23_C_3 map 10q26 1-10q26 2,
Homo sapiens
Homo sapiens chromosome 10 clone LA10NC01_23_C_3 map 10q26 1-10q26 2,
Homo sapiens
Homo sapiens chromosome 10 clone LA10NC01_23_C_3 map 10q26 1-10q26 2,
Homo sapiens
Homo sapiens chromosome 6 clone RP11-557H15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 6 clone RP11-557H15, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Saccharomyces cerevisiae chromosome VIII cosmid 9998.
Saccharomyces cerevisiae
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR04E21 (D592) RPCI-98 04.E.21 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04E21 (D592) RPCI-98 04.E.21 map
Drosophila melanogaster
Homo sapiens
H. sapiens FGF6 gene.
Homo sapiens
Homo sapiens
Comamonas testosteroni PtL5 cryptic plasmid pPT1, complete sequence.
Comamonas testosteroni
Comamonas testosteroni PtL5 cryptic plasmid pPT1, complete sequence.
Comamonas testosteroni
Homo sapiens Xp22 BAC GS279A12 (Genome Systems) complete sequence.
Homo sapiens
Homo sapiens
H. sapiens mRNA for cytochrome P-450.
Homo sapiens
Drosophila melanogaster
Homo sapiens
Mus musculus
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid F52G3.
Caenorhabditis elegans
Oryza sativa
D. melanogaster (Barton) SED5 mRNA.
Drosophila melanogaster
Drosophila melanogaster DNA sequence (P1 DS02740 (D27)), complete sequence.
Drosophila melanogaster
Danio rerio
Citrus tristeza virus complete genome, isolate T385.
Citrus tristeza virus
D. melanogaster (Barton) SED5 mRNA.
Drosophila melanogaster
Citrus tristeza virus defective RNA, strain T411.
Citrus tristeza virus
Corynebacterium glutamicum strain 22243 R-plasmid pAG1, complete sequence.
Corynebacterium
glutamicum
Homo sapiens
Corynebacterium glutamicum strain 22243 R-plasmid pAG1, complete sequence.
Corynebacterium
glutamicum
Rattus norvegicus
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 1/162.
Mycobacterium
tuberculosis
M. tuberculosis origin of replication and genes rnpA, rpmH, dnaA, dnaN, recF.
Mycobacterium
tuberculosis
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 16 clone 116B6, ***SEQUENCING IN PROGRESS***, 42
Homo sapiens
Arabidopsis thaliana chromosome II BAC F4I1 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Kluyveromyces lactis DNA fragment for sequence tagged site, clone okam5e06r.
Kluyveromyces lactis
Kluyveromyces lactis DNA fragment for sequence tagged site, clone okam5e06r.
Kluyveromyces lactis
Homo sapiens
Homo sapiens
Homo sapiens
Oryzias latipes Medaka OG-12 (MOG-12) mRNA, complete cds.
Oryzias latipes
Trypanosoma brucei
Trypanosoma brucei
Gallus gallus preprogastrin gene, complete cds.
Gallus gallus
Homo sapiens
H. sapiens PTP1C/HCP gene
Homo sapiens
Homo sapiens
Leishmania major chromosome 35 clone L7195 strain Friedlin, ***SEQUENCING IN
Leishmania major
Leishmania major chromosome 35 clone L7195 strain Friedlin, ***SEQUENCING IN
Leishmania major
Sus scrofa myogenic regulatory factor MyoD (myoD) gene, complete cds.
Sus scrofa
Bacteriophage c2 complete genome.
Lactococcus
bacteriophage c2
Zea mays
Bacteriophage c2 complete genome.
Lactococcus bacteriophage
Streptomyces coelicolor cosmid J1.
Streptomyces coelicolor
Pseudomonas aeruginosa PAO substrain OT684 pycverdine gene transcriptional regulator PvdS
Pseudomonas aeruginosa
Homo sapiens clone RP11-175P13, ***SEQUENCING IN PROGRESS***, 48 unordered
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid K02E7
Caenorhabditis elegans
Homo sapiens clone 7_J_14, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 7_J_14, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Homo sapiens clone 1_K_15, ***SEQUENCING IN PROGRESS***, 15 unordered pieces.
Homo sapiens
Homo sapiens clone 1_K_15, ***SEQUENCING IN PROGRESS***, 15 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.520_J_4, ***SEQUENCING IN PROGRESS***, 5 unordered pieces.
Homo sapiens
Homo sapiens chromosome 4 clone B150J4 map 4q25, complete sequence.
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1012F16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 20 clone RP5-1012F16, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 5p, BAC clone 50g21 (LBNL H154), complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR09A04 (D860) RPCI-98 09.A.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR09A04 (D860) RPCI-98 09.A.4 map
Drosophila melanogaster
Homo sapiens chromosome 17, clone HRPC41C23, complete sequence.
Homo sapiens
Rattus norvegicus
Homo sapiens
Rhodococcus opacus putative transposase gene, partial cds; and putative FAD synthetase,
Rhodococcus opacus
Drosophila melanogaster
Drosophila melanogaster
Rhodococcus opacus putative transposase gene, partial cds, and putative FAD synthetase,
Rhodococcus opacus
Gossypium hirsutum
Rhodococcus opacus putative transposase gene, partial cds; and putative FAD synthetase,
Rhodococcus opacus
Homo sapiens chromosome X clone cosmid 244B12 map Xq13, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome X clone cosmid 244B12 map Xq13, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 21 clone B753B2 map 21q21.2, ***SEQUENCING IN
Homo sapiens
Trichogramma australicum internal transcribed spacer 2, complete sequence.
Trichogramma
australicum
Homo sapiens
Homo sapiens
Arabidopsis thaliana chromosome 1 BAC T8F5 sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens clone NH0086N01, complete sequence.
Homo sapiens
Homo sapiens clone NH0086N01, complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR39F04 (D839) RPCI-98 39.F.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR39F04 (D839) RPCI-98 39.F.4 map
Drosophila melanogaster
Drosophila melanogaster chromosome X clone BACR30J04 (D908) RPCI-98 30.J.4 map
Drosophila melanogaster
Homo sapiens chromosome 16 clone RPCI-11_137H10, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_137H10, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 15 clone BAC 573G7 map 15q24, LOW-PASS SEQUENCE
Homo sapiens
Gallus gallus smooth muscle gamma actin (gamma actin) gene, complete cds.
Gallus gallus
Propionibacterium freudenreichii hemY, hemH, hemB, hemX, hemR and hemL genes, complete
Propionibacterium
freudenreichii
Propionibacterium freudenreichii hemY, hemH, hemB, hemX, hemR and hemL genes, complete
Propionibacterium
freudenreichii
Homo sapiens chromosome 4 clone RP3-323A24, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 4 clone RP3-323A24, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Homo sapiens PAC clone DJ0808A01 from 7q21.1-q31.1, complete sequence.
Homo sapiens
Homo sapiens chromosome 12q seeders clone RPCI11-185N2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 12q seeders clone RPCI11-185N2, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 8 clone RP11-4P3, ***SEQUENCING IN PROGRESS***, 5
Homo sapiens
Mus musculus DNA from BAC 10818 containing the Ercc-4 gene, complete sequence.
Mus musculus
Mus musculus DNA from BAC 10818 containing the Ercc-4 gene, complete sequence.
Mus musculus
Thermobifida fusca beta-1,4-exocellulase E6 precursor (celF) gene, complete cds; and unknown
Thermobifida fusca
Eikenella corrodens type IV pilin (pilA1), type IV pilin (pilA2), putative fimbrial protein (pilB),
Eikenella corrodens
E. corrodens ecpA and ecpB genes encoding type 4 N-methylphenylalanine pilin and hag1 gene
Eikenella corrodens
Thermotoga maritima section 19 of 136 of the complete genome.
Thermotoga maritima
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Mus musculus
Drosophila melanogaster genome survey sequence T7 end of BAC # BACR05B21 of RPCI-98
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR07H08 (D864) RPCI-98 07.H.8 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR07H08 (D864) RPCI-98 07.H.8 map
Drosophila melanogaster
Drosophila melanogaster, chromosome 2R, region 31C1-31D6, P1 clone DS08879, complete
Drosophila melanogaster
Homo sapiens
Caenorhabditis elegans clone Y32G9, ***SEQUENCING IN PROGRESS***, 9 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y32G9, ***SEQUENCING IN PROGRESS***, 9 unordered
Caenorhabditis elegans
Streptomyces coelicolor cosmid 2G5.
Streptomyces coelicolor
Oryza sativa genomic DNA, chromosome 1, clone:P0711E10.
Oryza sativa
Streptomyces coelicolor cosmid 2G5.
Streptomyces coelicolor
Mycobacterium tuberculosis H37Rv complete genome; segment 122/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 122/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome 8 clone RP11-4P3, ***SEQUENCING IN PROGRESS***, 5
Homo sapiens
Oryzias latipes Bf/C2 mRNA, complete cds.
Oryzias latipes
Homo sapiens chromosome 8 clone RP11-4P3, ***SEQUENCING IN PROGRESS***, 5
Homo sapiens
Mycobacterium avium acetolactate synthase (ilvBN) and acetohydroxy acid isomeroreductase
Mycobacterium avium
Homo sapiens PAC clone DJ0547C10 from 7p21-p22, complete sequence.
Homo sapiens
Homo sapiens PAC clone DJ0547C10 from 7p21-p22, complete sequence.
Homo sapiens
Caenorhabditis elegans clone Y38B5, ***SEQUENCING IN PROGRESS***, 12 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone W06H8, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone W06H8, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans cosmid W04G3, complete sequence.
Caenorhabditis elegans
Apium graveolens mannitol dehydrogenase (Mtd) gene, complete cds.
Apium graveolens
Caenorhabditis elegans cosmid W04G3, complete sequence.
Caenorhabditis elegans
Arabidopsis thaliana genomic DNA, chromosome 5, TAC clone: K24G6, complete sequence.
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Homo sapiens chromosome 11 clone 56_G_09 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone 56_G_09 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone 56_G_09 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Mus musculus
Neurospora crassa
Homo sapiens chromosome 1 clone RP4-658I14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 1 clone RP4-658I14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 1 clone RP4-658I14, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome X clone BACR41N19 (D907) RPCI-98 41.N.19 map
Drosophila melanogaster
Homo sapiens chromosome 17 clone HCIT7H10 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17 clone HCIT7H10 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17 clone HCIT7H10 map 17, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans clone Y108G3Y, ***SEQUENCING IN PROGRESS***, 4 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y108G3Y, ***SEQUENCING IN PROGRESS***, 4 unordered
Caenorhabditis elegans
E. coli chromosomal region from 76.0 to 81.5 minutes.
Escherichia coli
C. glutamicum panB, panC & xylB genes.
Corynebacterium
glutamicum
Homo sapiens chromosome 16 clone 165M1, ***SEQUENCING IN PROGRESS***, 105
Homo sapiens
Homo sapiens chromosome 16 clone 165M1, ***SEQUENCING IN PROGRESS***, 105
Homo sapiens
Caenorhabditis elegans cosmid H12I19, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans chromosome IV clone Y37A1, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome IV clone Y37A1, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Mus musculus
Mus musculus complement C3a anaphylatoxin receptor (C3ar) gene, complete cds.
Mus musculus
Mus musculus anaphylatoxin C3a receptor gene, complete cds.
Mus musculus
Brevibacterium lactofermentum phosphoenolpyruvate sugar phosphotransferase (ptsG) gene,
Brevibacterium
lactofermentum
Corynebacterium glutamicum phosphoenolpyruvate sugar phosphotransferase (ptsM) mRNA,
Corynebacterium
glutamicum
Corynebacterium glutamicum phosphoenolpyruvate sugar phosphotransferase (ptsM) mRNA,
Corynebacterium
glutamicum
Homo sapiens clone DJ0607J02, ***SEQUENCING IN PROGRESS***, 12 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0607J02, ***SEQUENCING IN PROGRESS***, 12 unordered pieces.
Homo sapiens
Molluscum contagiosum virus subtype 1, complete genome.
Molluscum contagiosum
Homo sapiens
Homo sapiens
Caenorhabditis elegans
elegans cDNA clone yk427e6 3′, mRNA sequence.
Caenorhabditis elegans cosmid C29H12.
Caenorhabditis elegans
Drosophila melanogaster genome survey sequence T7 end of BAC:BACR33I08 of RPCI-98
Drosophila melanogaster
H. sapiens gene for interleukin-1 receptor antagonist.
Homo sapiens
Homo sapiens IL-1 receptor antagonist IL-1Ra (IL-1RN) gene, alternatively spliced forms,
Homo sapiens
Homo sapiens
Methanococcus jannaschii section 2 of 150 of the complete genome.
Methanococcus jannaschii
Drosophila melanogaster
Drosophila melanogaster
Methanococcus jannaschii section 2 of 150 of the complete genome.
Methanococcus jannaschii
Methanococcus jannaschii section 2 of 150 of the complete genome.
Methanococcus jannaschii
Homo sapiens BAC clone GS170I02 from 7p21-p15.1, complete sequence.
Homo sapiens
Homo sapiens chromosome 16, cosmid clone 444B9 (LANL), complete sequence.
Homo sapiens
Homo sapiens immunoglobulin lambda gene locus DNA, clone:22A12.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Drosophila melanogaster DNA sequence (P1 DS05557 (D152)), complete sequence.
Drosophila melanogaster
Drosophila melanogaster
melanogaster cDNA clone SD02734 5prime, mRNA sequence.
Rattus sp.
Drosophila melanogaster genome survey sequence TET3 end of BAC # BACR21F10 of
Drosophila melanogaster
Homo sapiens chromosome 4 clone 21_G_20 map 4, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 4 clone 21_G_20 map 4, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens 12q24.2 PAC RPCI1-157K6 (Roswell Park Cancer Institute Human PAC library)
Homo sapiens
Homo sapiens, complete sequence.
Homo sapiens
Homo sapiens
C. glutamicum insertion sequence IS1207 and transposase gene.
Corynebacterium
glutamicum
S. cerevisiae chromosome IV cosmid 9320A.
Saccharomyces cerevisiae
S. cerevisiae chromosome IV cosmid 9320X.
Saccharomyces cerevisiae
Homo sapiens Xp22-150 BAC GSHB-309P15 (Genome Systems Human BAC Library)
Homo sapiens
Corynebacterium glutamicum putative type II 5-cytosoine methyltransferase (cgIIM) and
Corynebacterium
glutamicum
Corynebacterium glutamicum putative type II 5-cytosoine methyltransferase (cgIIM) and
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens clone RP11-83M17 from 7q31, complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR09I15 (D570) RPCI-98 09.I.15 map
Drosophila melanogaster
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 17 unordered pieces.
Homo sapiens
Drosophila melanogaster (P1 DS06754 (D83)) DNA sequence, complete sequence.
Drosophila melanogaster
Homo sapiens
Homo sapiens
Homo sapiens
Brugia malayi
Brugia malayi
Homo sapiens clone NH0364J06, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Homo sapiens clone NH0364J06, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
Homo sapiens clone NH0364J06, ***SEQUENCING IN PROGRESS***, 29 unordered pieces.
Homo sapiens
X. campestris xps E, F, G, H, I, and J genes for protein secretion and pathogenicity functions.
Xanthomonas campestris
Trypanosoma brucei
Homo sapiens
Homo sapiens clone NH0507C01, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Homo sapiens clone NH0507C01, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Homo sapiens clone NH0507C01, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Synechocystis sp. PCC6803 complete genome, 27/27, 3418852-3573470.
Synechocystis sp.
Mycobacterium tuberculosis H37Rv complete genome; segment 143/162.
Mycobacterium
tuberculosis
Bacillus subtilis complete genome (section 6 of 21); from 999501 to 1209940.
Bacillus subtilis
Homo sapiens chromosome 19 clone CIT978SKB_180A7, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CIT978SKB_180A7, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_362D12, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans clone Y74A11X, ***SEQUENCING IN PROGRESS***, 81 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y74A11X, ***SEQUENCING IN PROGRESS***, 81 unordered
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone Y70C5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Corynebacterium glutamicum ilvD gene.
Corynebacterium
glutamicum
Homo sapiens, complete sequence.
Homo sapiens
Homo sapiens, complete sequence.
Homo sapiens
Homo sapiens PAC clone DJ0910H09 from 7q21.1-q21.2, complete sequence.
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, segment 24/28, complete sequence.
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, SLC5A3-f4A4 region,
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 46/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome unknown clone NH0368K23, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0368K23, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome 15 clone 28_B_17 map 15, LOW-PASS SEQUENCE
Homo sapiens
Homo sapiens chromosome 15 clone 28_B_17 map 15, LOW-PASS SEQUENCE
Homo sapiens
Homo sapiens
Mus musculus
Caenorhabditis elegans chromosome V clone Y102A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome V clone Y102A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
C. glutamicum ORF3 and aroP gene.
Corynebacterium
glutamicum
C. glutamicum dapE gene and orf2.
Corynebacterium
glutamicum
Streptomyces coelicolor cosmid I7.
Streptomyces coelicolor
C. glutamicum dapE gene and orf2.
Corynebacterium
glutamicum
Homo sapiens chromosome 4 clone B386O24 map 4q25, complete sequence.
Homo sapiens
Mus musculus chromosome 6 clone 388_N_17 map 6, ***SEQUENCING IN
Mus musculus
Homo sapiens chromosome 18, clone RP11-31P16, complete sequence.
Homo sapiens
Homo sapiens chromosome 18, clone RP11-31P16, complete sequence.
Homo sapiens
Homo sapiens
Amycolatopsis orientalis cosmid PCZA361.
Amycolatopsis orientalis
Arabidopsis thaliana dal1 gene.
Arabidopsis thaliana
Homo sapiens chromosome 5, BAC clone 203o13 (LBNL H155), complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_365B8, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_365B8, ***SEQUENCING IN
Homo sapiens
Homo sapiens clone NH0098C01, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens clone NH0098C01, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens clone NH0098C01, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***, 3
Plasmodium falciparum
Plasmodium falciparum chromosome 12 clone 3D7, ***SEQUENCING IN PROGRESS***, 3
Plasmodium falciparum
Plasmodium falciparum
A. thaliana middle repetative sequence.
Arabidopsis thaliana
Arabidopsis thaliana chromosome II BAC F25P17 genomic sequence, complete sequence.
Arabidopsis thaliana
Lycopersicon esculentum
Drosophila melanogaster chromosome 3 clone BACR03D22 (D709) RPCI-98 03.D.22 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR03D22 (D709) RPCI-98 03.D.22 map
Drosophila melanogaster
Dictyostelium discoideum
Caenorhabditis elegans
elegans cDNA clone yk336c10 5′, mRNA sequence.
Caenorhabditis elegans
elegans cDNA clone yk230e7 5′, mRNA sequence.
Caenorhabditis elegans
elegans cDNA clone yk594g6 5′, mRNA sequence.
Drosophila melanogaster POU domain protein (pdm-1) gene, promoter region and exon 1.
Drosophila melanogaster
Mycobacterium tuberculosis H37Rv complete genome; segment 19/162.
Mycobacterium
tuberculosis
Danio rerio
Brevibacterium lactofermentum gene for alpha-ketoglutaric acid dehydrogenase.
Corynebacterium
glutamicum
Corynebacterium glutamicum DNA for 2-oxoglutarate dehydrogenase, complete cds.
Corynebacterium
glutamicum
Brevibacterium lactofermentum gene for alpha-ketoglutaric acid dehydrogenase.
Corynebacterium
glutamicum
Homo sapiens
Arabidopsis thaliana BAC T15B16.
Arabidopsis thaliana
Arabidopsis thaliana BAC T7B11 from chromosome IV near 10 cM, complete sequence.
Arabidopsis thaliana
Homo sapiens chromosome 5 clone CIT978SKB_3B12, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_3B12, ***SEQUENCING IN
Homo sapiens
Dictyostelium discoideum CRAC (dagA) gene, complete cds.
Dictyostelium discoideum
Homo sapiens
Homo sapiens DNA sequence from PAC 230G1 on chromosome Xp11.3. Contains EST, STS
Homo sapiens
Homo sapiens
Homo sapiens chromosome 11 clone 63_H_13 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone 63_H_13 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens DNA sequence from PAC 230G1 on chromosome Xp11.3. Contains EST, STS
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 53/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 53/162.
Mycobacterium
tuberculosis
Archaeoglobus fulgidus section 167 of 172 of the complete genome.
Archaeoglobus fulgidus
Homo sapiens
Homo sapiens chromosome 16 clone RPCI-11_538I12, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Mus musculus
F. rubripes GSS sequence, clone 137O18aC6, genomic survey sequence.
Fugu rubripes
Arabidopsis thaliana
Trypanosoma brucei
Trypanosoma brucei
Homo sapiens chromosome 8 clone 76_N_5 map 8, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Boreogadus saida antifreeze glycopeptide AFGP polyprotein precursor gene, complete cds.
Boreogadus saida
Chlamydia pneumoniae section 31 of 103 of the complete genome.
Chlamydophila
pneumoniae
Boreogadus saida antifreeze glycopeptide AFGP polyprotein precursor gene, complete cds.
Boreogadus saida
Homo sapiens clone NH0288C18, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens clone NH0288C18, complete sequence.
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, segment 2/28, complete sequence.
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML, f43D11-119B8 region, segment
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone f43D11-
Homo sapiens
Arabidopsis thaliana chromosome II BAC F3K23 genomic sequence, complete sequence.
Arabidopsis thaliana
S. cerevisiae chromosome XV DNA, 54.7 kb region.
Saccharomyces cerevisiae
Homo sapiens DNA for amyloid precursor protein, complete cds.
Homo sapiens
Lactobacillus helveticus cochaperonin GroES and chaperonin GroEL genes, complete cds; and
Lactobacillus helveticus
Corynebacterium glutamicum heat shock, ATP-binding protein (clpB) gene, complete cds.
Corynebacterium
glutamicum
Rhodopseudomonas sphaeroides fbc operon (fbcF, fbcB, fbcC genes).
Rhodobacter sphaeroides
Mus musculus casein kinase 2 beta subunit (gMCK2) gene, partial cds; BAT4, NG20 (NG20),
Mus musculus
Mus musculus
Rattus sp.
Rhizobium meliloti RmDEGP (degP) gene, complete cds.
Sinorhizobium meliloti
Homo sapiens
Mus musculus
Drosophila melanogaster laminin alpha 1,2 (wing blister) mRNA, complete cds.
Drosophila melanogaster
Drosophila melanogaster (P1 DS01068 (D37)) DNA sequence, complete sequence.
Drosophila melanogaster
Arabidopsis thaliana
Arabidopsis thaliana
Mus musculus
Mus musculus
Escherichia coli K-12 chromosomal region from 67.4 to 76.0 minutes.
Escherichia coli
Escherichia coli K-12 MG1655 section 284 of 400 of the complete genome.
Escherichia coli
E. coli mpB gene and ORFs.
Escherichia coli
Synechocystis sp. PCC6803 complete genome, 14/27, 1719644-1848241.
Synechocystis sp.
Homo sapiens
Synechocystis sp. PCC6803 complete genome, 14/27, 1719644-1848241.
Synechocystis sp.
Drosophila melanogaster DNA sequence (P1 DS00913 (D24)), complete sequence.
Drosophila melanogaster
Drosophila melanogaster
Mesembryanthemum
Mesembryanthemum crystallinum cDNA clone L0-1173 5′ similar to Profilin 1 (AF092547)
crystallinum
Sinorhizobium meliloti dissimilatory nitrous oxide reduction proteins NosY, NosL and NosX
Sinorhizobium meliloti
Sinorhizobium meliloti dissimilatory nitrous oxide reduction proteins NosY, NosL and NosX
Sinorhizobium meliloti
Streptococcus pneumoniae serotype 19A DexB (dexB) gene, partial sequence; capsular
Streptococcus pneumoniae
Streptococcus pneumoniae type 19A putative oligosaccharide repeat unit transporter (cps19AJ)
Streptococcus pneumoniae
Mus musculus
Homo sapiens PAC clone DJ0744D13 from 7q11, complete sequence.
Homo sapiens
Homo sapiens
Haemophilus influenzae Rd section 78 of 163 of the complete genome.
Haemophilus influenzae
Mycobacterium tuberculosis H37Rv complete genome; segment 44/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 44/162.
Mycobacterium
tuberculosis
Trypanosoma brucei
Homo sapiens
Homo sapiens
Caenorhabditis elegans chromosome IV clone Y116A8, ***SEQUENCING IN
Caenorhabditis elegans
Caenorhabditis elegans cosmid Y116A8B, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans chromosome IV clone Y116A8, ***SEQUENCING IN
Caenorhabditis elegans
Drosophila melanogaster chromosome 3 clone BACR45M03 (D718) RPCI-98 45.M.3 map
Drosophila melanogaster
Caenorhabditis elegans cosmid T02C5.
Caenorhabditis elegans
Caenorhabditis elegans cosmid ZC101, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans
elegans cDNA clone yk459c11 5′, mRNA sequence.
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_432B14, ***SEQUENCING IN
Homo sapiens
Streptomyces coelicolor cosmid 6G10.
Streptomyces coelicolor
Mycobacterium leprae cosmid B1554 DNA sequence.
Mycobacterium leprae
Mycobacterium leprae cosmid B1551 DNA sequence.
Mycobacterium leprae
Homo sapiens chromosome 1, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens chromosome 1, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens
Streptomyces coelicolor cosmid 6G10.
Streptomyces coelicolor
Drosophila melanogaster chromosome 3 clone BACR29J02 (D817) RPCI-98 29.J.2 map
Drosophila melanogaster
Homo sapiens
Homo sapiens Chromosome 22q11.2 Cosmid Clone 20b in DGCR Region, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Nephila clavipes minor ampullate silk protein MiSp1 mRNA, partial cds.
Nephila clavipes
Homo sapiens
Oryza sativa
Streptomyces venezuelae bacteriophage VWB orfs.
Bordetella bronchiseptica LysR transcriptional activator homolog (bbuR), urease accessory
Bordetella bronchiseptica
Homo sapiens
Homo sapiens genomic DNA, chromosome 6q27, complete sequence.
Homo sapiens
Theileria parva strain KNP2 p67 surface antigen (p67) gene, complete cds.
Theileria parva
Theileria parva strain Hluhluwe3 p67 surface antigen (p67) gene, complete cds.
Theileria parva
Neurospora crassa
Mycobacterium leprae cosmid B1351.
Mycobacterium leprae
Mycobacterium leprae cosmid B1351.
Mycobacterium leprae
B. ammoniagenes FAS gene.
Corynebacterium
ammoniagenes
Mycobacterium leprae cosmid L458.
Mycobacterium leprae
Homo sapiens
Mus musculus partial b3 gene for alpha3 subunit of L-type Ca2+ channel, exons 2-13.
Mus musculus
Rattus norvegicus
Mus musculus voltage-dependent calcium channel beta-3 subunit (CCHB3) mRNA,
Mus musculus
Homo sapiens chromosome 17 clone RP11-952N18 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 17 clone RP11-952N18 map 17, ***SEQUENCING IN
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, Q78C10-149C3 region,
Homo sapiens
Rattus sp.
Homo sapiens
Homo sapiens
Homo sapiens clone DJ1015O24, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens clone DJ1015O24, ***SEQUENCING IN PROGRESS***, 3 unordered pieces.
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, B335D16-P10G11 region,
Homo sapiens
Streptomyces coelicolor cosmid 6C5.
Streptomyces coelicolor
Homo sapiens chromosome 11 clone 364_C_06 map 11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone 364_C_06 map 11, ***SEQUENCING IN
Homo sapiens
Solanum tuberosum NADH nitrate reductase (StNR2) mRNA, complete cds.
Solanum tuberosum
Lycopersicon esculentum
Lycopersicon esculentum
Mycobacterium tuberculosis H37Rv complete genome; segment 40/162.
Mycobacterium
tuberculosis
M. leprae genomic sequence, cosmid b1935.
Mycobacterium leprae
Mycobacterium leprae cosmid B57.
Mycobacterium leprae
Pyrococcus abyssi complete genome; segment 3/6.
Pyrococcus abyssi
Homo sapiens clone MS2304L04, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Homo sapiens clone MS2304L04, ***SEQUENCING IN PROGRESS***, 4 unordered pieces.
Homo sapiens
Lycopersicon esculentum
Lycopersicon esculentum
Homo sapiens chromosome 17, clone hRPK.1090_M_7, complete sequence.
Homo sapiens
Homo sapiens chromosome 17 clone hRPC.1030_A_12 map 17, ***SEQUENCING IN
Homo sapiens
Drosophila melanogaster peroxidasin precursor mRNA, complete cds.
Drosophila melanogaster
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone:T293,
Homo sapiens
Cyanidioschyzon merolae DNA for actin, complete cds.
Cyanidioschyzon merolae
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone:T293,
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 68 unordered pieces.
Homo sapiens
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 68 unordered pieces.
Homo sapiens
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 68 unordered pieces.
Homo sapiens
Mus musculus chromosome 10 clone 644_M_8 map 10, ***SEQUENCING IN
Mus musculus
Mus musculus chromosome 10 clone 644_M_8 map 10, ***SEQUENCING IN
Mus musculus
Mus musculus chromosome 10 clone 644_M_8 map 10, ***SEQUENCING IN
Mus musculus
Rattus norvegicus oxytocin receptor (OTR) gene, promoter region.
Rattus norvegicus
Rattus norvegicus oxytocin receptor (OTR) gene, promoter region.
Rattus norvegicus
Homo sapiens chromosome 5 clone CIT978SKB_194J6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_194J6, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_194J6, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Caenorhabditis elegans clone Y40C5, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone Y40C5, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Caenorhabditis elegans
Drosophila melanogaster chromosome 3 clone BACR29J02 (D817) RPCI-98 29.J.2 map
Drosophila melanogaster
Homo sapiens chromosome 19 clone CITB-H1_2369P2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CITB-H1_2369P2, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans clone Y67D8x, ***SEQUENCING IN PROGRESS***, 23 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y67D8x, ***SEQUENCING IN PROGRESS***, 23 unordered
Caenorhabditis elegans
Caenorhabditis elegans clone Y67D8x, ***SEQUENCING IN PROGRESS***, 23 unordered
Caenorhabditis elegans
Homo sapiens
Homo sapiens
Corynebacterium glutamicum multidrug resistance protein (cmr) gene, complete cds.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid K08B5.
Caenorhabditis elegans
Arabidopsis thaliana chromosome II BAC F15K19 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens Xp22 BAC GSHB-590J6 (Genome Systems Human BAC library) complete
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR03L02 (D766) RPCI-98 03.L.2 map
Drosophila melanogaster
Mycobacterium tuberculosis H37Rv complete genome; segment 62/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 62/162.
Mycobacterium
tuberculosis
Homo sapiens ELK1 pseudogene (ELK2) and immunoglobulin heavy chain gamma pseudogene
Homo sapiens
Homo sapiens
Drosophila melanogaster (P1 DS03431 (D102)) DNA sequence, complete sequence.
Drosophila melanogaster
Homo sapiens
Oryza sativa
Oryza sativa
Homo sapiens clone NH0376O14, complete sequence.
Homo sapiens
Bacillus sp.
Saccharomyces cerevisiae
N. meningitidis lipA and lipB genes for LipA and LipB proteins.
Neisseria meningitidis
Homo sapiens chromosome 21 clone B753B2 map 21q21.2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 21 clone B753B2 map 21q21.2, ***SEQUENCING IN
Homo sapiens
Homo sapiens clone NH0536I18, complete sequence.
Homo sapiens
Caenorhabditis elegans cosmid C54C6, complete sequence.
Caenorhabditis elegans
Homo sapiens chromosome 5 clone CITB-H1_2259I14, ***SEQUENCING IN
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR10E03 (D690) RPCI-98 10 E.3 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR10E03 (D690) RPCI-98 10.E.3 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR01C11 (D819) RPCI-98 01.C.11 map
Drosophila melanogaster
Drosophila melanogaster (P1 DS00329 (D89)) DNA sequence, complete sequence.
Drosophila melanogaster
Drosophila melanogaster (P1 DS00329 (D89)) DNA sequence, complete sequence.
Drosophila melanogaster
Mycobacterium tuberculosis H37Rv complete genome; segment 89/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 155/162.
Mycobacterium
tuberculosis
Arabidopsis thaliana
Arabidopsis thaliana chromosome I BAC T28P6 genomic sequence, complete sequence.
Arabidopsis thaliana
Homo sapiens chromosome 15 clone 8_C_22 map 15, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 15 clone 8_C_22 map 15, ***SEQUENCING IN
Homo sapiens
Mus musculus
Homo sapiens
Homo sapiens
Homo sapiens
Yersinia pestis hypothetical protein (yceG) gene, partial cds; thymidylate kinase (tmk) gene,
Yersinia pestis
Homo sapiens
Homo sapiens
Yersinia pestis hypothetical protein (yceG) gene, partial cds; thymidylate kinase (tmk) gene,
Yersinia pestis
Rattus norvegicus rab3 effector (RIM) mRNA, alternatively spliced, complete cds.
Rattus norvegicus
Echinococcus granulosus 18S ribosomal RNA gene, complete sequence.
Echinococcus granulosus
Corynebacterium glutamicum L-aspartate-alpha-decarboxylase precursor (panD) gene, complete
Corynebacterium
glutamicum
Corynebacterium glutamicum L-aspartate-alpha-decarboxylase precursor (panD) gene, complete
Corynebacterium
glutamicum
Corynebacterium glutamicum L-aspartate-alpha-decarboxylase precursor (panD) gene, complete
Corynebacterium
glutamicum
Mycobacterium tuberculosis H37Rv complete genome; segment 144/162.
Mycobacterium
tuberculosis
Mus musculus
Homo sapiens chromosome 5 clone CIT-HSPC_551I11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_551I11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_551I11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 4, ***SEQUENCING IN PROGRESS***, 18 unordered pieces.
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2292M9, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2292M9, ***SEQUENCING IN
Homo sapiens
Amycolatopsis mediterranei genes encoding rifamycin polyketide synthases, ORFs 1 to 5.
Amycolatopsis
mediterranei
Amycolatopsis mediterranei rifamycin biosynthetic gene cluster.
Amycolatopsis
mediterranei
Drosophila melanogaster chromosome 2 clone BACR04E19 (D1026) RPCI-98 04.E.19 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR04E19 (D1026) RPCI-98 04.E.19 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2R, region 34B6-34C2, P1 clone DS08787, complete
Drosophila melanogaster
Homo sapiens clone NH0541E12, WORKING DRAFT SEQUENCE, 1 unordered pieces.
Homo sapiens
Homo sapiens clone NH0541E12, WORKING DRAFT SEQUENCE, 1 unordered pieces.
Homo sapiens
Homo sapiens clone 7_H_4, LOW-PASS SEQUENCE SAMPLING.
Homo sapiens
Burkholderia pseudomallei strain 1026b DbhB (dbhB), general secretory pathway protein D
Burkholderia pseudomallei
P. chlororaphis genes for amidase (EC 3.5.1.4) and for nitrile hydratase (EC 4.2.1.84).
Pseudomonas
Rhodococcus rhodochrous
Corynebacterium glutamicum pyc gene.
Corynebacterium
glutamicum
Homo sapiens chromosome 17, clone hRPK.855_D_21, complete sequence.
Homo sapiens
Homo sapiens
Kluyveromyces lactis transcriptional activator (GAL11) gene, complete cds.
Kluyveromyces lactis
Homo sapiens partial gene for caspase-9, intronic sequence (584 bp).
Homo sapiens
Kluyveromyces lactis transcriptional activator (GAL11) gene, complete cds.
Kluyveromyces lactis
Corynebacterium glutamicum thiosulfate sulfurtransferase (thtR) gene, partial cds, acyl CoA
Corynebacterium
glutamicum
Sorghum bicolor BAC clone 25 M18, complete sequence.
Sorghum bicolor
Homo sapiens clone DJ1164F05, complete sequence.
Homo sapiens
Corynebacterium glutamicum thiosulfate sulfurtransferase (thtR) gene, parital cds, acyl CoA
Corynebacterium
glutamicum
Mycobacterium tuberculosis H37Rv complete genome, segment 49/162.
Mycobacterium
tuberculosis
Homo sapiens partial gene for caspase-9, intronic sequence (584 bp).
Homo sapiens
Homo sapiens
Homo sapiens chromosome 18 clone 263_O_14 map 18, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 18 clone 263_O_14 map 18, ***SEQUENCING IN
Homo sapiens
Melanoplus sanguinipes entomopoxvirus, complete genome.
Melanoplus sanguinipes
entomopoxvirus
Homo sapiens chromosome 2 clone 303_K_20 map 2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 2 clone 303_K_20 map 2, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.215_E_13, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.215_E_13, complete sequence.
Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Homo sapiens cosmid LM1937 from Xq28.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 123/162.
Mycobacterium
tuberculosis
S. reticuli gene encoding Msik protein and orf1.
Streptomyces reticuli
Mycobacterium tuberculosis sequence from clone y414a.
Mycobacterium
tuberculosis
Bacillus subtilis complete genome (section 21 of 21) from 3999281 to 4214814.
Bacillus subtilis
Homo sapiens
Bacillus subtilis complete genome (section 21 of 21) from 3999281 to 4214814.
Bacillus subtilis
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid Y53H1C, complete sequence.
Caenorhabditis elegans
Caenorhabditis elegans cosmid K04F10.
Caenorhabditis elegans
Arabidopsis thaliana genomic DNA, chromosome 5, P1 clone: MHK7, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana genomic DNA, chromosome 5, P1 clone: MHK7, complete sequence.
Arabidopsis thaliana
Homo sapiens
Homo sapiens
Pristionchus pacificus
Streptomyces coelicolor cosmid F76.
Streptomyces coelicolor
Corynebacterium
glutamicum
Arabidopsis thaliana chromosome 1 BAC T24D18 sequence, complete sequence.
Arabidopsis thaliana
C. glutamicum proA gene.
Corynebacterium
glutamicum
C. glutamicum proA gene.
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens chromosome 17, clone hRPC.1171_I_10, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPC.1171_I_10, complete sequence.
Homo sapiens
Homo sapiens
Streptomyces coelicolor cosmid 51A.
Streptomyces coelicolor
Pseudomonas aeruginosa MexZ (mexZ), complete cds; and mexGH operon, complete sequence.
Pseudomonas aeruginosa
Pseudomonas aeruginosa gene for MexX and MexY, complete cds.
Pseudomonas aeruginosa
Rhodobacter capsulatus cosmids 143-147, complete sequence.
Rhodobacter capsulatus
Arabidopsis thaliana chromosome 1 BAC T2K10 sequence, complete sequence.
Arabidopsis thaliana
Arabidopsis thaliana BAC T24H24.
Arabidopsis thaliana
Streptomyces coelicolor cosmid 5F2A.
Streptomyces coelicolor
C. glutamicum betP gene.
Corynebacterium
glutamicum
Liquidambar formosane internal transcribed spacer 1, 5.8S ribosomal RNA gene; and internal
Liquidambar formosana
Rhizobium sp. NGR234 plasmid pNGR234a, section 7 of 46 of the complete plasmid sequence.
Rhizobium sp. NGR234
Rhizobium sp. NGR234 plasmid pNGR234a, section 7 of 46 of the complete plasmid sequence.
Rhizobium sp. NGR234
Chromatium vinosum recA gene.
Allochromatium vinosum
Homo sapiens
Homo sapiens
C. glutamicum (ATCC 13032) aceB gene.
Corynebacterium
glutamicum
Corynebacterium glutamicum malate synthase (aceB) gene, complete cds.
Corynebacterium
glutamicum
Caenorhabditis elegans cosmid K06A4, complete sequence.
Caenorhabditis elegans
Drosophila melanogaster
H. sapiens mRNA for RNA polymerase II largest subunit.
Homo sapiens
H. sapiens mRNA for RNA polymerase II largest subunit.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 59/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y151.
Mycobacterium
tuberculosis
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster
Leishmania major chromosome 35 clone L165 strain Friedlin, ***SEQUENCING IN
Leishmania major
Corynebacterium glutamicum murl gene for D-glutamate racemase, complete cds.
Corynebacterium
glutamicum
Mus musculus
Mus musculus transgelin mRNA, complete cds.
Mus musculus
Homo sapiens
Homo sapiens
Danio rerio
Drosophila melanogaster chromosome 2 clone DS08537 (D425) map 50C1-50C2 strain y2;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS07345 (D445) map 50C1-50C2 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS00096 (D427) map 50C1-50C4 strain y;
Drosophila melanogaster
Pseudomonas fluorescens genes encoding p-hydroxycinnamoyl CoA hydratase/lyase and
Pseudomonas fluorescens
Onchocerca volvulus
Onchocerca volvulus cDNA clone SWOvAFCAP31F09 5′, mRNA sequence.
Xanthomonas campstris HrpA1 gene, complete cds.
Xanthomonas campestris
Cyprinus carpio IL-1 gene for interleukin-1-beta.
Cyprinus carpio
Cyprinus carpio mRNA for interleukin-1 beta, complete cds.
Cyprinus carpio
Cyprinus carpio IL-1 gene for interleukin-1-beta.
Cyprinus carpio
Caenorhabditis elegans cosmid Y40B1B, complete sequence.
Caenorhabditis elegans
Homo sapiens
Caenorhabditis elegans cosmid Y40B1B, complete sequence.
Caenorhabditis elegans
Mycobacterium tuberculosis H37Rv complete genome; segment 83/162.
Mycobacterium
tuberculosis
Homo sapiens clone DJ164D05, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens chromosome 15 clone RP11-519C12, WORKING DRAFT SEQUENCE, 16
Homo sapiens
Homo sapiens chromosome 15 clone RP11-519C12, WORKING DRAFT SEQUENCE, 16
Homo sapiens
Homo sapiens
Drosophila melanogaster, chromosome 2R, region 59B4-59B7, P1 clone DS02885, complete
Drosophila melanogaster
Drosophila melanogaster, chromosome 2R, region 59B4-59B7, P1 clone DS02885, complete
Drosophila melanogaster
Mus musculus calcium and DAG-regulated guanine nucleotide exchange factor I mRNA,
Mus musculus
Drosophila melanogaster chromosome 3L/75C1 clone RPCI98-35F4, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster chromosome 3L/75C1 clone RPCI98-35F4, ***SEQUENCING IN
Drosophila melanogaster
Homo sapiens
Streptomyces coelicolor cosmid F76.
Streptomyces coelicolor
Homo sapiens
Homo sapiens chromosome 17 clone 20D5, ***SEQUENCING IN PROGRESS***, 10
Homo sapiens
Oryza sativa
Oryza sativa
Drosophila melanogaster chromosome 3 clone BACR14A01 (D720) RPCI-98 14 A.1 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR14A01 (D720) RPCI-98 14.A.1 map
Drosophila melanogaster
Homo sapiens chromosome 19, cosmid R33729, complete sequence.
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR03P13 (D672) RPCI-98 03.P.13 map
Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR03P13 (D672) RPCI-98 03.P.13 map
Drosophila melanogaster
Corynebacterium glutamicum 5-enolpyruvylshikimate 3-phosphate synthase (aroA) gene,
Corynebacterium
glutamicum
Caenorhabditis elegans chromosome IV clone Y45F10, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome IV clone Y45F10, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Mus musculus
Mus musculus
Homo sapiens chromosome 19 clone CITB-E1_3023J11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CITB-E1_3023J11, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 19 clone CITB-E1_3023J11, ***SEQUENCING IN
Homo sapiens
Homo sapiens PAC clone DJ1098B01 from 7q11.23-q21, complete sequence.
Homo sapiens
Homo sapiens
Photobacterium leiognathi probable flavin reductase (luxG) gene, complete cds.
Photobacterium leiognathi
Drosophila melanogaster
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome 2 clone DS02336 (D440) map 60C8-60D2 strain y;
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone DS02336 (D440) map 60C8-60D2 strain y;
Drosophila melanogaster
Homo sapiens 12q24.1 PAC RPCI3-521E19 (Roswell Park Cancer Institute Human PAC
Homo sapiens
Homo sapiens
Caenorhabditis elegans cosmid R09H3.
Caenorhabditis elegans
Homo sapiens
Caenorhabditis elegans chromosome X clone Y7A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans chromosome X clone Y7A5, ***SEQUENCING IN PROGRESS***,
Caenorhabditis elegans
Caenorhabditis elegans cosmid Y7A5A, complete sequence.
Caenorhabditis elegans
Brevibacterium saccharolyticum gene for L-2.3-butanediol dehydrogenase, complete cds.
Brevibacterium
saccharolyticum
Mycoplasma arthritidis bacteriophage MAV1, complete genome.
Mycoplasma arthritidis
Mycobacterium tuberculosis H37Rv complete genome; segment 108/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome X clone bWXD40, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Homo sapiens
Homo sapiens chromosome X clone bWXD40, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Coturnix coturnix pro-alpha2(I) collagen mRNA, partial cds.
Coturnix coturnix
Sartorya fumigate nucleolar protein AfCbf5p (AfCBF5p) mRNA, complete cds.
Aspergillus fumigatus
Rhizobium sp. NGR234 plasmid pNGR234a, section 43 of 46 of the complete plasmid
Rhizobium sp. NGR234
Homo sapiens chromosome 17 clone 20D5, ***SEQUENCING IN PROGRESS***, 10
Homo sapiens
Homo sapiens chromosome 17 clone 20D5, ***SEQUENCING IN PROGRESS***, 10
Homo sapiens
Homo sapiens angiotensin I converting enzyme precursor (DCP1) gene, alternative splice
Homo sapiens
R. leguminosarum Symbiosis Plasmid DNA, rlvCP gene.
Rhizobium leguminosarum
Rhizobium leguminosarum bv. viciae putative glycerol-3-phosphate transport protein (ugpC)
Rhizobium leguminosarum
Neisseria gonorrhoeae ribokinase (rbk) gene, 3′ end; ADP-L-glycero-D-mannoheptose
Neisseria gonorrhoeae
Caenorhabditis elegans cosmid M02D8.
Caenorhabditis elegans
Caenorhabditis elegans cosmid C36C5.
Caenorhabditis elegans
Homo sapiens chromosome 19 clone CIT-HSPC_457E21, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans clone Y43H11, ***SEQUENCING IN PROGRESS***, 7 unordered pieces.
Caenorhabditis elegans
Caenorhabditis elegans clone Y43H11, ***SEQUENCING IN PROGRESS***, 7 unordered pieces.
Caenorhabditis elegans
Drosophila melanogaster chromosome 3L/74B2 clone RPCO98-6H1, ***SEQUENCING IN
Drosophila melanogaster
Oryza sativa
Oryza sativa mRNA for sucrose transporter, complete cds.
Oryza sativa
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 129/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 129/162.
Mycobacterium
tuberculosis
Homo sapiens chromosome 20 clone RP5-901O8 map q11.1-11.23, ***SEQUENCING IN
Homo sapiens
Caenorhabditis elegans
Caenorhabditis elegans cosmid C10F3.
Caenorhabditis elegans
Trypanosoma cruzi
Corynebacterium glutamicum L-proline:NADP+ 5-oxidoreductase (proC) gene, complete cds.
Corynebacterium
glutamicum
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone B355D16-
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, B335D16-P10G11 region,
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 25/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid B2168.
Mycobacterium leprae
Streptomyces coelicolor cosmid E68.
Streptomyces coelicolor
Mus musculus
Mus musculus
Mus musculus TCR beta locus from bases 501860 to 700960 (section 3 of 3) of the complete
Mus musculus
Sus scrofa
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens, clone hRPK.12_A_1, complete sequence.
Homo sapiens
Homo sapiens, clone hRPK.12_A_1, complete sequence.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 64/162.
Mycobacterium
tuberculosis
Homo sapiens
Escherichia coli K-12 MG1655 section 116 of 400 of the complete genome.
Escherichia coli
Drosophila melanogaster neuroglian (nrg) gene, exons 3-6, 7a, 7b and alternatively spliced
Drosophila melanogaster
Drosophila melanogaster DNA sequence (P1 DS01962 (D216)), complete sequence.
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR08I18 (D660) RPCI-98 08.I.18 map 56A2-
Drosophila melanogaster
Homo sapiens
Homo sapiens chromosome 19 clone LLNL-R_245B6, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 19 clone LLNL-R_245B6, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Streptomyces coelicolor cosmid C22.
Streptomyces coelicolor
Bacillus subtilis complete genome (section 17 of 21), from 3197001 to 3414420.
Bacillus subtilis
Mycobacterium leprae cosmid L536.
Mycobacterium leprae
C. elegans cosmid F42H10.
Caenorhabditis elegans
Caenorhabditis elegans Bristol N2 GTPase-activating protein (CEGAP) mRNA, partial cds.
Caenorhabditis elegans
C. elegans cosmid F42H10.
Caenorhabditis elegans
Oryza sativa
Caenorhabditis elegans
Caenorhabditis elegans
Homo sapiens
Arabidopsis thaliana DNA chromosome 4, ESSA I FCA contig fragment No. 3.
Arabidopsis thaliana
Arabidopsis thaliana DNA chromosome 4, ESSA I FCA contig fragment No. 3.
Arabidopsis thaliana
Drosophila melanogaster chromosome 2 clone BACR05E17 (D1059) RPCI-98 05.E.17 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR05E17 (D1059) RPCI-98 05.E.17 map
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR05E17 (D1059) RPCI-98 05.E.17 map
Drosophila melanogaster
Homo sapiens
A. xylinum aceB, aceC, aceD, and aceE genes.
Acetobacter xylinus
A. xylinum aceB, aceC, aceD, and aceE genes.
Acetobacter xylinus
Mycobacterium tuberculosis H37Rv complete genome; segment 18/162.
Mycobacterium
tuberculosis
M. tuberculosis dnaK, grpE, and dnaJ genes.
Mycobacterium
tuberculosis
Rhodococcus rhodochrous gene for 3-ketosteroid-delta1-dehydrogenase, complete cds.
Rhodococcus rhodochrous
Streptomyces sp.
Homo sapiens chromosome 5 clone CIT-HSPC_459H20, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_459H20, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone P1_889E7, ***SEQUENCING IN PROGRESS***, 67
Homo sapiens
Homo sapiens chromosome 5 clone P1_889E7, ***SEQUENCING IN PROGRESS***, 67
Homo sapiens
Homo sapiens chromosome 5 clone P1_1352A1, ***SEQUENCING IN PROGRESS***, 19
Homo sapiens
Homo sapiens clone RPCI5-951N9, ***SEQUENCING IN PROGRESS***, 41 unordered pieces.
Homo sapiens
Escherichia coli genomic DNA. (23.0-23.4 min).
Escherichia coli
Homo sapiens clone RPCI5-951N9, ***SEQUENCING IN PROGRESS***, 41 unordered pieces.
Homo sapiens
C. glutamicum DNA, attachment site bacteriophage Phi-16.
Corynebacterium
glutamicum
Archaeoglobus fulgidus section 12 of 172 of the complete genome.
Archaeoglobus fulgidus
Homo sapiens
Homo sapiens
Homo sapiens
M. edulis gene for polyphenolic adhesive protein.
Mytilus edulis
Homo sapiens PAC clone DJ076B20 from 22, complete sequence.
Homo sapiens
Homo sapiens PAC clone DJ076B20 from 22, complete sequence.
Homo sapiens
Haemophilus influenzae Rd section 145 of 163 of the complete genome.
Haemophilus influenzae
F. rubripes GSS sequence, clone 042H13bD8, genomic survey sequence.
Fugu rubripes
F. rubripes GSS sequence, clone 042H13aE5, genomic survey sequence.
Fugu rubripes
F. rubripes GSS sequence, clone 042H13aH5, genomic survey sequence.
Fugu rubripes
Homo sapiens PAC clone DJ1143H19 from 7p14-p15, complete sequence.
Homo sapiens
Homo sapiens chromosome 2 clone 101B6 map 2p11, complete sequence.
Homo sapiens
Homo sapiens chromosome 17 clone 6_M_14 map 17, ***SEQUENCING IN
Homo sapiens
F. tularensis 16S rRNA.
Francisella tularensis
F. tularensis 16S rRNA.
Francisella tularensis
F. philomiragia 16S rRNA.
Francisella philomiragia
Homo sapiens
Homo sapiens
Homo sapiens jerky gene product homolog mRNA, complete cds.
Homo sapiens
Corynebacterium glutamicum multidrug resistance protein (cmr) gene, complete cds.
Corynebacterium
glutamicum
Lycopersicon esculentum
Mus musculus
Streptomyces coelicolor cosmid GD3.
Streptomyces coelicolor
Mus musculus
Homo sapiens iduronate sulphate sulphatase (IDS) gene, complete cds.
Homo sapiens
Homo sapiens
X. laevis mRNA for transcription factor (clone XLFB1a1).
Xenopus laevis
Homo sapiens clone NH0512E16, complete sequence.
Homo sapiens
Pilayella littoralis ribosomal protein S14 (rps14) gene, partial cds; ATPase subunit 8 (atp8)
Mitochondrion Pilayella
littoralis
Homo sapiens
Pilayella littoralis ribosomal protein S14 (rps14) gene, partial cds; ATPase subunit 8 (atp8)
Mitochondrion Pilayella
littoralis
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone Q78C10-
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens genomic DNA of 21q22.1, GART and AML related, Q78C10-149C3 region,
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, D21S226-AML region, clone Q78C10-
Homo sapiens
Homo sapiens genomic DNA, chromosome 21q22.1, segment 18/26, complete sequence.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 12/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 131/162.
Mycobacterium
tuberculosis
Homo sapiens clone NH0309L06, ***SEQUENCING IN PROGRESS***, 2 unordered pieces.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 12/162.
Mycobacterium
tuberculosis
Mycobacterium leprae cosmid L622.
Mycobacterium leprae
Chloroblum limicola atp2 operon.
Chlorobium limicola
Drosophila melanogaster genome survey sequence T7 end of BAC # BACR11M23 of RPCI-98
Drosophila melanogaster
Drosophila melanogaster genome survey sequence T7 end of BAC # BACR11M23 of RPCI-98
Drosophila melanogaster
Plasmodium falciparum MAL3P5, complete sequence.
Plasmodium falciparum
Arabidopsis thaliana genomic DNA, chromosome 5, TAC clone: K15O15, complete sequence.
Arabidopsis thaliana
Methanobacterium thermoautotrophicum from bases 1592014 to 1607566 (section 136 of 148)
Methanobacterium
thermoautotrophicum
Drosophila melanogaster DNA sequence (P1 DS07134 (D192)), complete sequence.
Drosophila melanogaster
Arabidopsis thaliana chromosome I BAC F13F21 genomic sequence, complete sequence.
Arabidopsis thaliana
Mycobacterium tuberculosis H37Rv complete genome, segment 157/162.
Mycobacterium
tuberculosis
Sphingomonas sp. A8AN3 catechol 2,3-dioxygenase gene, complete cds and 2-hydroxymuconic
Sphingomonas sp. A8AN3
Sphingomonas sp. A8AN3 catechol 2,3-dioxygenase gene, complete cds and 2-hydroxymuconic
Sphingomonas sp. A8AN3
Homo sapiens ES/130 mRNA, complete cds.
Homo sapiens
Homo sapiens ES/130 mRNA, complete cds.
Homo sapiens
Homo sapiens
Chlamydomonas reinhardtii histone H3, histone H4, histone H2B, and histone H2A genes,
Chlamydomonas
reinhardtii
Homo sapiens
Homo sapiens
C. melassecola gene for extracellular antigen PS1.
Corynebacterium
melassecola
C. glutamicum cop1 gene for PS1.
Corynebacterium
glutamicum
Homo sapiens genomic DNA of 21q22.1, GART and AML, f43D11-119B8 region, segment
Homo sapiens
Drosophila melanogaster chromosome 3 clone BACR01A18 (D669) RPCI-98 01.A.18 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR01A18 (D669) RPCI-98 01.A.18 map
Drosophila melanogaster
Drosophila melanogaster chromosome 3 clone BACR20D10 (D667) RPCI-98 20.D.10 map
Drosophila melanogaster
Pseudomonas aeruginosa MexZ (mexZ), complete cds; and mexGH operon, complete sequence.
Pseudomonas aeruginosa
Pseudomonas aeruginosa gene for MexX and MexY, complete cds.
Pseudomonas aeruginosa
Homo sapiens (subclone 7_e4 from P1 H25) DNA sequence, complete sequence.
Homo sapiens
Homo sapiens chromosome 5 clone P1_660D11, ***SEQUENCING IN PROGRESS***, 28
Homo sapiens
Homo sapiens chromosome 5 clone P1_660D11, ***SEQUENCING IN PROGRESS***, 28
Homo sapiens
Corynebacterium glutamicum yjcc gene, amtR gene and citE gene, partial.
Corynebacterium
glutamicum
Corynebacterium glutamicum yjcc gene, amtR gene and citE gene, partial.
Corynebacterium
glutamicum
Mus musculus
Corynebacterium glutamicum yjcc gene, amtR gene and citE gene, partial.
Corynebacterium
glutamicum
Corynebacterium glutamicum yjcc gene, amtR gene and citE gene, partial.
Corynebacterium
glutamicum
Oryza sativa
Homo sapiens clone DJ0042M02, ***SEQUENCING IN PROGRESS***, 13 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0042M02, ***SEQUENCING IN PROGRESS***, 13 unordered pieces.
Homo sapiens
Homo sapiens clone DJ0810E06, complete sequence.
Homo sapiens
Mycobacterium tuberculosis sequence from clone y409.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis H37Rv complete genome; segment 158/162.
Mycobacterium
tuberculosis
Caenorhabditis elegans clone Y43H11, ***SEQUENCING IN PROGRESS***, 7 unordered
Caenorhabditis elegans
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Corynebacterium
glutamicum
Synechocystis sp. PCC6803 complete genome, 6/27, 630555-781448.
Synechocystis sp.
Homo sapiens
Synechocystis sp. PCC6803 complete genome, 6/27, 630555-781448.
Synechocystis sp.
Bacteroides fragilis capsular polysaccharide biosynthesis operon, complete sequence.
Bacteroides fragilis
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 36 unordered pieces.
Homo sapiens
Homo sapiens chromosome 7, ***SEQUENCING IN PROGRESS***, 36 unordered pieces.
Homo sapiens
Mus musculus
Homo sapiens
Homo sapiens
Drosophila melanogaster chromosome 2 clone BACR07I11 (D648) RPCI-98 07.I.11 map 58A1-
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR07I11 (D648) RPCI-98 07.I.11 map 58A1-
Drosophila melanogaster
Drosophila melanogaster chromosome 2 clone BACR07I11 (D648) RPCI-98 07.I.11 map 58A1-
Drosophila melanogaster
Homo sapiens chromosome X clone bWXD40, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Homo sapiens chromosome X clone bWXD40, ***SEQUENCING IN PROGRESS***, 2
Homo sapiens
Trypanosoma brucei
Homo sapiens chromosome 9 clone hRPK.85_O_21 map 9, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 9 clone hRPK.85_O_21 map 9, ***SEQUENCING IN
Homo sapiens
Synechococcus PCC7942 UDP-N-acetylmuramate-alanine ligase (murC) gene, partial cds,
Synechococcus PCC7942
Mycobacterium tuberculosis H37Rv complete genome, segment 151/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y23.
Mycobacterium
tuberculosis
Lycopersicon esculentum
Homo sapiens
Caenorhabditis elegans cosmid C50A2.
Caenorhabditis elegans
Caenorhabditis elegans clone Y104H12b, ***SEQUENCING IN PROGRESS***, 3 unordered
Caenorhabditis elegans
Homo sapiens chromosome 11 clone PAC2 map 11q11, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens chromosome 11 clone PAC2 map 11q11, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens
Mycobacterium leprae cosmid B268.
Mycobacterium leprae
Mycobacterium leprae cosmid B1554 DNA sequence.
Mycobacterium leprae
Mycobacterium leprae cosmid B1551 DNA sequence.
Mycobacterium leprae
Homo sapiens chromosome 5 clone CIT978SKB_17P2, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT978SKB_17P2, ***SEQUENCING IN
Homo sapiens
Archaeoglobus fulgidus section 162 of 172 of the complete genome.
Archaeoglobus fulgidus
C. glutamicum pheA gene encoding prephenate dehydratase, complete cds.
Corynebacterium
glutamicum
Homo sapiens clone hRPK.74_A_1, ***SEQUENCING IN PROGRESS***, 10 unordered pieces.
Homo sapiens
Homo sapiens clone hRPK.74_A_1, ***SEQUENCING IN PROGRESS***, 10 unordered pieces.
Homo sapiens
Homo sapiens
Anas platyrhynchos
Anas platyrhynchos
Homo sapiens chromosome unknown clone NH0364A16, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0364A16, WORKING DRAFT SEQUENCE, in
Homo sapiens
Fischerella muscicola small subunit ribosomal RNA gene, partial sequence.
Fischerella muscicola
Homo sapiens
Drosophila melanogaster chromosome 3L/70C12 clone RPCI98-2M13, ***SEQUENCING IN
Drosophila melanogaster
Drosophila melanogaster
Corynebacterium glutamicum gene for MurC, FtsQ, FtsZ, complete cds.
Corynebacterium
glutamicum
Homo sapiens PAC clone DJ1166G19 from 7p12-p11.2, complete sequence.
Homo sapiens
Homo sapiens chromosome X clone RP4-657D12 map q22.1-24, ***SEQUENCING IN
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Streptomyces coelicolor cosmid F85.
Streptomyces coelicolor
Homo sapiens chromosome 15 clone 334_M_8 map 15, LOW-PASS
Homo sapiens
Homo sapiens clone NH0575J05, ***SEQUENCING IN PROGRESS***, 1 unordered pieces.
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 50/162.
Mycobacterium
tuberculosis
Mycobacterium tuberculosis sequence from clone y348.
Mycobacterium
tuberculosis
Homo sapiens genomic DNA of 21q22.1, GART and AML related, Q78C10-149C3 region,
Homo sapiens
Corynebacterium glutamicum chorismate synthase (aroC), shikimate kinase (aroK), and 3-
Corynebacterium
glutamicum
Corynebacterium glutamicum dehydroquinate synthetase (aroB) gene, complete cds.
Corynebacterium
glutamicum
B. subtilis thrZ downstream chromosomal region.
Bacillus subtilis
AL080253
Arabidopsis thaliana DNA chromosome 4, BAC clone F9F13 (ESSA project).
Arabidopsis thaliana
Arabidopsis thaliana DNA chromosome 3, BAC clone T29H11.
Arabidopsis thaliana
Arabidopsis thaliana
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.293_K_20, complete sequence.
Homo sapiens
Homo sapiens chromosome 17, clone hRPK.293_K_20, complete sequence.
Homo sapiens
Corynebacterium glutamicum gene for MurC, FtsQ, FtsZ, complete cds.
Corynebacterium
glutamicum
B. lactofermentum murC, ftsQ or divD & ftsZ genes.
Corynebacterium
glutamicum
Homo sapiens chromosome 11 clone 381_O_22 map 11, ***SEQUENCING IN
Homo sapiens
B. lactofermentum murC, ftsQ or divD & ftsZ genes.
Corynebacterium
glutamicum
Corynebacterium glutamicum gene for MurC, FtsQ, FtsZ, complete cds.
Corynebacterium
glutamicum
Streptomyces coelicolor cosmid I51.
Streptomyces coelicolor
Corynebacterium glutamicum multidrug resistance protein (cmr) gene, complete cds.
Corynebacterium
glutamicum
Oryza sativa
Thiobacillus neapolitanus carboxysome operon, complete sequence.
Thiobacillus neapolitanus
Mycobacterium tuberculosis H37Rv complete genome, segment 96/162.
Mycobacterium
tuberculosis
M. tuberculosis Ag84 (CIE) gene.
Mycobacterium
tuberculosis
Aeropyrum pernix genomic DNA, section 7/7.
Aeropyrum pernix
T. vulgaris cpT gene for carboxypeptidase T.
Thermoactinomyces
vulgaris
Homo sapiens
Mus musculus
Corynebacterium
glutamicum
Magnaporthe grisea
Glycine max
Homo sapiens DNA, DLEC1 to ORCTL4 gene region, section 1/2 (DLEC1, ORCTL3,
Homo sapiens
Homo sapiens DNA, DLEC1 to ORCTL4 gene region, section 1/2 (DLEC1, ORCTL3,
Homo sapiens
Homo sapiens genomic DNA, chromosome 3p21.3, clone:603 to 320, anti-oncogene region,
Homo sapiens
Homo sapiens chromosome unknown clone NH0002I08, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0002I08, WORKING DRAFT SEQUENCE, in
Homo sapiens
Homo sapiens chromosome unknown clone NH0002I08, WORKING DRAFT SEQUENCE, in
Homo sapiens
Cricetulus sp.
Homo sapiens chromosome 14 clone R-1017G21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-1017G21, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Rat vacuolar protein sorting homolog r-vps33b mRNA, complete cds.
Rattus norvegicus
Rat vacuolar protein sorting homolog r-vps33b mRNA, complete cds.
Rattus norvegicus
Homo sapiens
Nicotiana tabacum DNA fragment for K-alpha right T-DNA border.
Nicotiana tabacum
Homo sapiens chromosome 19 clone LLNL-F_192H5, ***SEQUENCING IN PROGRESS***,
Homo sapiens
Homo sapiens
Homo sapiens
Mycobacterium tuberculosis H37Rv complete genome; segment 57/162.
Mycobacterium
tuberculosis
Corynebacterium glutamicum dipeptide-binding protein (dciAE) gene, partial cds; adenine
Corynebacterium
glutamicum
Ictalurus punctalus estrogen receptor type alpha mRNA, complete cds.
Ictalurus punctatus
M. musculus rearranged T-cell receptor beta variable region (Vb17a).
Mus musculus
Homo sapiens chromosome 21 clone PAC 31K18 map 21q22.3, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 21 clone PAC 31K18 map 21q22.3, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 21q22.3 PAC 141B3, complete sequence, containing ribosomal
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
Rattus norvegicus A-kinase anchor protein mRNA, complete cds.
Rattus norvegicus
Gossypium hirsutum
Homo sapiens clone NH0223I10, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Homo sapiens
Homo sapiens clone NH0223I10, ***SEQUENCING IN PROGRESS***, 16 unordered pieces.
Homo sapiens
Borrelia burgdorferi (section 23 of 70) of the complete genome.
Borrelia burgdorferi
Glycine max
Homo sapiens chromosome 5 clone CITB-H1_2319M24, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CITB-H1_2319M24, ***SEQUENCING IN
Homo sapiens
Homo sapiens genomic DNA of 9q32 anti-oncogene of flat epitherium cancer, segment 8/10.
Homo sapiens
Homo sapiens
Homo sapiens genomic DNA of 9q32 anti-oncogene of flat epitherium cancer, segment 8/10.
Homo sapiens
Homo sapiens
Homo sapiens 12p13.3 PAC RPCI5-1103G8 (Roswell Park Cancer Institute Human PAC
Homo sapiens
Homo sapiens 12p13.3 PAC RPCI5-1103G8 (Roswell Park Cancer Institute Human PAC
Homo sapiens
S. hygroscopicus gene cluster for polyketide immunosuppressant rapamycin.
Streptomyces
hygroscopicus
S. hygroscopicus gene cluster for polyketide immunosuppressant rapamycin.
Streptomyces
hygroscopicus
D. silvestris clone U28T2 non-LTR retrotransposon DNA (5218 bp).
Drosophila silvestris
D. silvestris clone U28T2 non-LTR retrotransposon DNA (7779 bp).
Drosophila silvestris
Mycoplasma pneumoniae cosmid pcos MPGT9 25kb EcoRi fragment.
Mycoplasma pneumoniae
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_229L21, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 5 clone CIT-HSPC_229L21, ***SEQUENCING IN
Homo sapiens
Homo sapiens
Homo sapiens
Homo sapiens
S. cerevisiae chromosome II reading frame ORF YBL033c.
Saccharomyces cerevisiae
S. cerevisiae RIB1 gene encoding GTP cyclohydrolase II.
Saccharomyces cerevisiae
Saccharomyces cerevisiae
Mus musculus
Homo sapiens
Streptomyces coelicolor cosmid E94.
Streptomyces coelicolor
Homo sapiens clone RPCI11-656E20, ***SEQUENCING IN PROGRESS***, 90 unordered pieces.
Homo sapiens
Homo sapiens clone RPCI11-656E20, ***SEQUENCING IN PROGRESS***, 90 unordered pieces.
Homo sapiens
Homo sapiens
Xenopus laevis potassium channel beta 2 subunit mRNA, partial cds.
Xenopus laevis
Homo sapiens chromosome 11 clone P28D2 map 11q13, ***SEQUENCING IN
Homo sapiens
Homo sapiens chromosome 11 clone P28D2 map 11q13, ***SEQUENCING IN
Homo sapiens
Mus musculus
Homo sapiens
Thermotoga maritima section 43 of 136 of the complete genome.
Thermotoga maritima
Giardia intestinalis histone H4 gene, complete cds.
Giardia intestinalis
Drosophila melanogaster chromosome X clone BACR48L05 (D1142) RPCI-98 48.L.5 map
Drosophila melanogaster
Drosophila melanogaster
Pseudomonas aeruginosa mucC and mucD genes, complete cds.
Pseudomonas aeruginosa
Pseudomonas aeruginosa alternate sigma factor (algU), mucA, mucB, mucC and mucD
Pseudomonas aeruginosa
Pseudomonas aeruginosa alternate sigma factor (algU), mucA, mucB, and mucC and mucD
Pseudomonas aeruginosa
Corynebacterium glutamicum acetohydroxy acid synthase (ilvB) and (ilvN) genes, and
Corynebacterium
glutamicum
Homo sapiens
Homo sapiens
Z. mays alcohol dehydrogenase (ADH-1 C-m allele) gene, complete cds.
Zea mays
Z. mays DNA for Adh1-Cm allele.
Zea mays
Z. mays alcohol dehydrogenase (ADH-1 C-m allele) gene, complete cds.
Zea mays
Oryza sativa receptor-like protein kinase gene, complete cds.
Oryza sativa
Homo sapiens chromosome 14 clone R-1089B7, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Homo sapiens chromosome 14 clone R-1089B7, ***SEQUENCING IN PROGRESS***, in
Homo sapiens
Zea mays thiamine biosynthetic enzyme (thi1-1) mRNA, complete cds.
Zea mays
Homo sapiens
Drosophila melanogaster
Lactobacillus sakei transcription-repair coupling factor (mfd) gene, partial cds; L-lactate
Lactobacillus sakei
Listeria monocytogenes transcription-repair coupling factor (mfdL), low temperature
Listeria monocytogenes
Drosophila melanogaster chromosome 3 clone BACR09F18 (D812) RPCI-98 09.F.18 map
Drosophila melanogaster
Rhizobium sp. NGR234 plasmid pNGR234a, section 6 of 46 of the complete plasmid sequence.
Rhizobium sp. NGR234
Sus scrofa p55 TNF receptor mRNA, complete cds.
Sus scrofa
Rhizobium sp. NGR234 plasmid pNGR234a, section 6 of 46 of the complete plasmid sequence.
Rhizobium sp. NGR234
Escherichia coli chromosome minutes 6-8.
Escherichia coli
Escherichia coli K-12 MG1655 section 35 of 400 of the complete genome.
Escherichia coli
E. coli orf302, 0rf303 and orf101 sequence.
Escherichia coli
Homo sapiens
P. sativum mRNA for ferritin.
Pisum sativum
P. sativum mRNA for ferritin.
Pisum sativum
Sorghum halepense
Homo sapiens
Gallus gallus neurocan core protein precursor, mRNA, complete cds.
Gallus gallus
Homo sapiens chromosome 19, cosmid R30813, complete sequence.
Homo sapiens
Homo sapiens chromosome 19, cosmid F19544, complete sequence.
Homo sapiens
Homo sapiens chromosome 19, cosmid R30813, complete sequence.
Homo sapiens
Homo sapiens
Homo sapiens
Mycobacterium leprae cosmid B13 DNA sequence.
Mycobacterium leprae
Homo sapiens chromosome 15 clone 76_D_16 map 15, LOW-PASS SEQUENCE
Homo sapiens
Homo sapiens chromosome 15 clone 76_D_16 map 15, LOW-PASS SEQUENCE
Homo sapiens
Corynebacterium glutamicum dtsR1 and dtsR2 genes, complete cds.
Corynebacterium
glutamicum
Brevibacterium lactofermentum dtsR and dtsR2 genes.
Corynebacterium
glutamicum
Canis familiaris delayed rectifier K+ channel mRNA, partial cds.
Canis familiaris
This application claims benefit of prior filed U.S. Provisional Patent Application Ser. No. 60/142,764, filed Jul. 8, 1999, and U.S. Provisional Patent Application Ser. No. 60/152,318, filed Sep. 3, 1999. The entire contents of both of the aforementioned applications are hereby expressly incorporated herein by reference.
| Number | Name | Date | Kind |
|---|---|---|---|
| 5554534 | Michaels et al. | Sep 1996 | A |
| 5665872 | Saito et al. | Sep 1997 | A |
| Number | Date | Country | |
|---|---|---|---|
| 60152318 | Sep 1999 | US | |
| 60142764 | Jul 1999 | US |
