Identification of genes associated with growth in plants

Abstract

Genes, nucleic acids and polypeptides associated with growth traits in plants are provided. Related probes, antibodies, marker sets, and arrays are provided as well as methods for predicting plant growth traits.

Description

COPYRIGHT NOTIFICATION

[0003] Pursuant to 37 C.F.R. 1.71(e), Applicants note that a portion of this disclosure contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.

FIELD OF THE INVENTION

[0004] This invention is in the field of genes which control growth traits in plants. The present invention relates, e.g., to the identification of candidate genes associated with growth in plants, polypeptides encoded by these genes, related probes, marker sets, methods for predicting the presence of growth traits in plants, and the like.

BACKGROUND OF THE INVENTION

[0005] Improvement of plant crops has generally proceeded incrementally through the intentional and/or incidental selection of individual plants with desired traits for cultivation. Crossing of unique individuals can result in vigorous individual hybrid plants with desirable characteristics. These established methods of hybrid generation and selection have provided mankind with vastly improved crop plants, but continued improvement by these methods is slow and unpredictable.

[0006] Plant growth traits are among the most important crop characteristics in commercial agriculture. The green revolution has increased plant growth rates with fertilizers and inhibited plant (weed) growth through herbicide application, providing significant improvements in crop yields to feed the world population since at least the 1960s. However, marginal improvements in green revolution technologies are tapering off and new approaches are needed to increase the productivity of agriculture.

[0007] Agricultural biotechnology can provide a directed approach to enhancing the quality and quantity of crops. Identification of genes associated with a desired plant characteristic, or trait, can be the first step to control of the trait. Gene recombination technologies can be employed to incorporate the identified genes into expression systems which can modulate display of a trait, screen for plants having a trait, and/or screen for additional genes associated with the trait. Plant growth traits are of special significance in agriculture, and identification of genes controlling plant growth is critical to providing food for the growing world population. Thus, identification and characterization of gene(s) controlling plant characteristics is of great interest, and will be of significant scientific and commercial importance.

[0008] The present invention relates to the identification of genes associated with plant growth traits. Polypeptides encoded by these genes, as well as related probes, marker sets, and methods for predicting growth traits in plants, as well as other features, will become apparent upon review of the following materials.

SUMMARY OF THE INVENTION

[0009] The present invention relates to a set of polynucleotide sequences which control growth traits in plants, exemplified by, e.g., SEQ ID NO: 1 through SEQ ID NO: 30 and, e.g., a set of polypeptide sequences which control growth traits in plants, exemplified by, e.g., SEQ ID NO: 31 through SEQ ID NO: 60.

[0010] In a first aspect, the invention relates to compositions including one or more nucleic acid expression vectors which include the polynucleotide sequences of the invention. For example, such expression vectors include nucleic acids including at least one polynucleotide sequence selected from SEQ ID NOs: 1-30. Similarly, sequences that hybridize under stringent hybridization conditions, or that are at least about 70%, (or at least about 75%, about 80%, about 85%, about 90%, about 95%, about 97%, about 98%, or at least about 99%) identical to one or more of SEQ ID NO: 1-30 can be included in the expression vectors of the invention. In addition, expression vectors, including polynucleotide sequences that encode a polypeptide sequence selected from among SEQ ID NO: 31-SEQ ID NO: 60, or conservative variations thereof, are compositions of the invention. Likewise, expression vectors incorporating nucleic acids with subsequences of at least 10 contiguous nucleotides of, e.g., SEQ ID NOs: 1-30 (or at least 12, 14, 16, or 17 or more contiguous nucleotides of one of the designated sequences) are included among the compositions of the invention. The polynucleotide sequences of the invention also include polynucleotide sequences complementary to any one of the above polynucleotide sequences described above. In some embodiments, the expression vector includes a promoter operably linked to one or more of the nucleic acids described above. Such expression vectors can encode expression products such as sense or antisense RNAs, or polypeptides.

[0011] Polypeptides having an amino acid sequence selected from the group consisting of SEQ ID NO: 31 to SEQ ID NO: 60, and conservative variants thereof, are also a feature of the invention, as are polypeptides encoded by a polynucleotide sequence of the invention (e.g., SEQ ID NO: 1-SEQ ID NO: 30, sequences that hybridize under stringent conditions to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that are at least about 70% identical to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that encode a polypeptide or conservative variations any such sequences, or subsequences thereof). Polypeptides (and oligopeptides and peptides) including amino acid subsequences of SEQ ID NO: 31 through SEQ ID NO: 60 are also a feature of the invention. For example, fusion proteins including a polypeptide of SEQ ID NO: 31 through SEQ ID NO: 60, or a subsequence, e.g., an antigenic subsequence, thereof are included in the polypeptides of the invention. Likewise, proteins having a sequence selected from SEQ ID NO: 31 to SEQ ID NO: 60, and homologous or variant polypeptides, and a peptide or polypeptide tag, such as a reporter peptide or polypeptide, localization signal or sequence, or antigenic epitope, are included among the polypeptides of the invention.

[0012] Cells comprising an expression vector, and/or expressing a polypeptide as described above, are also a feature of the invention. In certain embodiments, the expressed polypeptide can be encoded by an exogenous polynucleotide, e.g., an expression vector. Such expression vectors typically include a polynucleotide sequence encoding the polypeptide of interest operably linked to, and under the transcriptional regulation of, a constitutive or inducible promoter. In other embodiments, the polypeptide is encoded by an endogenous polynucleotide sequence activated by an exogenous promoter and/or enhancer.

[0013] Antibodies specific for the polypeptides of the invention, e.g., SEQ ID NO: 31-SEQ ID NO: 60, and conservatively modified variants, etc., are also a feature of the invention. Such specific antibodies can be either derived from a polyclonal antiserum or can be monoclonal antibodies. For example, such antibodies are specific for an epitope including or derived from a subsequence of one of SEQ ID NO: 31-SEQ ID NO: 60.

[0014] Another aspect of the invention provides labeled nucleic acid or polypeptide probes. For example, nucleic acid probes of the invention include DNA or RNA molecules incorporating a polynucleotide sequence of the invention e.g., selected from SEQ ID NO: 1-SEQ ID NO: 30, sequences that hybridize under stringent conditions to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that are at least about 70% identical to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that encode a polypeptide selected from SEQ ID NO: 1-SEQ ID NO: 30, sequences complementary to any such sequences, or a subsequence thereof including at least 10 contiguous nucleotides. Optionally, the subsequences include at least 12 contiguous nucleotides of one of, e.g., SEQ ID NOs: 1-30. Often such subsequences include at least 14 contiguous nucleotides, typically at least 16 contiguous nucleotides, and usually at least 17 or more contiguous nucleotides, e.g., of SEQ ID NO: 1 to SEQ ID NO: 30. These nucleic acid probes can be, e.g., synthetic oligonucleotides and probes, cDNA molecules, amplification products (e.g., produced by PCR or LCR), transcripts, or restriction fragments. In other embodiments, the labeled probes are polypeptides, such as polypeptides with amino acid sequences corresponding to SEQ ID NOs: 31-60, or subsequences thereof (e.g., peptide subsequence comprising at least six amino acids), including peptide subsequences. Antibodies specific for such polypeptides or peptides are also a feature of the invention (as are polypeptides which bind to such antibodies). For example, a polypeptide probe can be a fusion protein, or a polypeptide with an epitope tag. A peptide probe can be an antigenic peptide derived from one of SEQ ID NO: 31 through SEQ ID NO: 60.

[0015] The label of the nucleic acid, polypeptide or antibody probe can be any of a variety of detectable moieties including isotopic, fluorescent, fluorogenic, or colorimetric labels.

[0016] In another aspect, the invention relates to a marker set, e.g., for predicting at least one growth trait of a plant cell. Such marker sets can include a plurality of members, where the members comprise nucleic acids, polypeptides, and/or peptides, and/or antibodies. Marker sets can include two or more of one type of member, or optionally can include one or more of two or more different types of members. For example, marker sets can include a plurality of nucleic acids including one or more polynucleotide sequence selected from SEQ ID NO: 1 to SEQ ID NO: 30, or SEQ ID NO: 61 to SEQ ID NO: 403, or conservative modifications thereof; polynucleotide sequences that hybridize under stringent hybridization conditions, or that are at least about 70%, (or at least about 75%, 80%, 85%, 90%, 95%, 97%, 98%, or at least about 99%) identical to one or more of SEQ ID NOs: 1-30; sequences complementary to any such sequences or subsequences thereof including at least 10 contiguous nucleotides of, e.g., SEQ ID NOs: 1-30 (or at least 12, 14, 16, 17 or more contiguous nucleotides of one of the designated sequences).

[0017] In one embodiment, the marker set includes a plurality of oligonucleotides, such as synthetic oligonucleotides. In other embodiments, the marker set includes expression products, amplification products, nucleic acid probes, or the like. The marker set of the invention can also include multiple nucleic acids selected from among different molecular classifications, e.g., oligonucleotides, expression products (such as cDNAs), amplification products, restriction fragments, etc. In one embodiment, the marker set is made up of nucleic acids including polynucleotide sequences corresponding to each of SEQ ID NO: 1 through SEQ ID NO: 30, or a subsequence selected from each of SEQ ID NO: 1 through SEQ ID NO: 30, or their compliments. In one embodiment, the marker set is made up of a plurality or a majority of members that together comprise a plurality, majority, or all of sequences or subsequences selected from a plurality, a majority or each nucleic acid represented by SEQ ID NO: 61-SEQ ID NO: 403, or their compliments.

[0018] Markers of the invention can also be polypeptides, e.g., polypeptides encoded by SEQ ID NO: 31-SEQ ID NO: 60, or polypeptide or peptide subsequences thereof. Typically, a peptide subsequence comprises, e.g., at least about 6 contiguous amino acids, 10 contiguous amino acids or more, often at least about 15 contiguous amino acids, and frequently at least about 20 contiguous amino acids of, e.g., one of SEQ ID NOs: 31-60.

[0019] Markers of the invention can also be antibodies, e.g., monoclonal or polyclonal antibodies, or anti-sera specific for an epitope derived from a polypeptide of the invention, e.g., one or more of SEQ ID NO: 31 through SEQ ID NO: 60.

[0020] In certain useful embodiments, the marker set is logically or physically arrayed. For example, the members of the marker set, whether nucleic acid, polypeptide, peptide or antibody, or a combination thereof, can be physically arrayed in a solid phase or liquid phase array, such as a bead (or microbead) array. Arrays, including a plurality of SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 31-SEQ ID NO: 60, SEQ ID NO: 61-SEQ ID NO: 403, or antibodies specific therefor, are also a feature of the invention. In some embodiments, the arrays include members corresponding to a majority of SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 61-SEQ ID NO: 403, SEQ ID NO: 31 to SEQ ID NO: 60, or antibodies specific therefor. In one embodiment, the array includes members corresponding to each of SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 31 to SEQ ID NO: 60, or antibodies specific therefor. In an embodiment, the marker set is comprised of at least 10 contiguous nucleotides of each of SEQ ID NO: 61-SEQ ID NO: 403, at least 10 contiguous nucleotides of a plurality of SEQ ID NO: 61-SEQ ID NO: 403, at least 10 contiguous nucleotides of a majority of SEQ ID NO: 61-SEQ ID NO: 403, or complimentary sequences thereof. In an embodiment, the marker set is a mixed marker set including members that are selected from nucleic acids, polypeptides or peptides, and antibodies.

[0021] In one embodiment, the marker set of the invention is used to predict at least one growth trait of a plant cell by hybridizing one or more nucleic acids of the marker set to a DNA or RNA sample from a cell or tissue, and detecting at least one polymorphic polynucleotide or differentially expressed expression product in the sample. In another related embodiment, differentially expressed expression products are detected using an array, e.g., an antibody array.

[0022] Another aspect of the invention provides methods for modulating a plant growth trait. The methods of the invention for modulating plant growth in a cell or tissue optionally include modulating expression or activity of at least one polypeptide encoded by a nucleic acid with a polynucleotide sequence selected from SEQ ID) NO: 1 to SEQ ID NO: 30, or conservative modifications thereof; a polynucleotide sequence encoding a polypeptide sequence selected from SEQ ID NO: 31 to SEQ ID NO: 60; a polynucleotide sequence that hybridizes under stringent hybridization conditions, or that is at least 70%, (or at least 75%, 80%, 85%, 90%, 95%, 97%, 98%, or at least 99%) identical to at least one of SEQ ID NOs: 1-30; sequences complementary to any such sequences, or subsequences thereof including at least 10 contiguous nucleotides of, e.g., SEQ ID NOs: 1-30 (or at least 12, 14, 16, 17 or more contiguous nucleotides of one of the designated sequences).

[0023] In one embodiment, plant growth is regulated by modulating expression or activity of at least one polypeptide contributing to a plant growth trait. The modulation of plant growth traits can be done in variety of plants, e.g., flowering plants, a member of the family of Brassicaceae, or Arabidopsis, Brassica, Zea, Oryza, Triticum, Hordeum, Lolium, Sorghum, Glycine, Medicago, Helianthus, Lactuca, Beta, Vitis, Solanum, Lycopersicon, Capsicum, Gossypium, Hevea, Linum, Prunus, Citrus, Populus, Pinus, Quercus, Aspergillus, Neurospora, Candida and Saccharomyces. In an embodiment, expression is modulated by expressing an exogenous nucleic acid including a polynucleotide sequence selected from SEQ ID NO: 1 to SEQ ID NO: 30. In other embodiments, expression of an endogenous nucleic acid, such as an endogenous nucleic acid encoding one of SEQ ID NO: 31 through SEQ ID NO: 60 is induced or suppressed, for example, by introducing, e.g., integrating, an exogenous nucleic acid including at least one promoter that regulates expression of the endogenous nucleic acid. In other embodiments, altered expression or activity of an expression product encoded by a nucleic acid, e.g., a polynucleotide sequence selected from SEQ ID NO: 1 to SEQ ID NO: 30 or conservative varients thereof, is detected, e.g., in a high throughput assay.

[0024] In some embodiments, expression or activity is modulated in response to an environmental factor, a chemical or biological agent, a pathogen, a bacteria, a virus, a fungus or an insect. An aspect of the invention includes methods which involve detecting altered expression or activity of an expression product, such as an RNA or polypeptide, encoded by a nucleic acid including a polynucleotide sequence selected from, e.g., SEQ ID NO: 1 to SEQ ID NO: 30. In some cases, altered expression or activity in response to the presence of a fertilizer or a herbicide is detected. In certain embodiments, a plurality of expression products are detected, e.g., in an array, a bead array or in a high-throughput assay.

[0025] In an embodiment, a data record related to the altered expression or activity is recorded in a database. For example, a data record can be a character string recorded in a data base made up of a plurality of character strings recorded in a computer or on a computer readable medium.

[0026] In another aspect, the invention provides methods for detecting genes for a plant growth trait. The methods of the invention for detecting genes for a plant growth trait involve providing a subject cell or tissue sample of nucleic acids and detecting at least one polynucleotide sequence or expression product corresponding to a polynucleotide sequence of the invention, e.g., such as a polynucleotide sequence selected from SEQ ID NO: 1-SEQ ID NO: 30, sequences that hybridize under stringent conditions to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that are at least about 70% (or at least 75%, 80%, 85%, 90%, 95%, 97%, 98%, or at least 99%) identical to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that encode a polypeptide encoded by any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences complementary to any such sequences, or subsequences thereof including at least 10 contiguous nucleotides, e.g., of SEQ ID NOs: 1-30 (or at least 12, 14, 16, or 17 or more contiguous nucleotides of one of the designated sequences.

[0027] Detection of expression products is performed either qualitatively (presence or absence of one or more product of interest) or quantitatively (by monitoring the level of expression of one or more product of interest). In one embodiment, the expression product is an RNA expression product, such as differentially expressed RNA. The present invention optionally includes monitoring an expression level of a nucleic acid or polypeptide as noted herein for detection of a plant growth trait in a plant or in a population of plants.

[0028] Kits which incorporate one or more of the nucleic acids, polypeptides, antibodies, or arrays noted above are also a feature of the invention. Such kits can include any of the above noted components and further include, e.g., instructions for use of the components in any of the methods noted herein, packaging materials, containers for holding the components, and/or the like.

[0029] Digital systems which incorporate one or more representation (e.g., character string, data table, or the like) of one or more of the nucleic acids or polypeptides herein are also a feature of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0030] FIG. 1 shows a chart of differential gene expression between a plant having long roots and a plant having short roots versus chromosome position. A QTL plot for association with root length is also mapped on the same genome.

[0031] FIG. 2 shows Arabidopsis QTL plots for three growth related traits (root length, aerial mass, and root mass). The LOD score for association of each marker interval in the genome with each phenotype is shown.

DETAILED DISCUSSION

[0032] Control of plant growth is perhaps the most important goal in modern agriculture. The rate of plant growth, overall yield of usable plant mass, fertilizer response, and sensitivity to herbicides can all affect a farmer's productivity. First, the rate of plant growth can be critical, e.g., where growing seasons are short, where several crops are planted each year, or for long growing crops such as lumber. Second, maximum growth in the usable plant mass is desirable, e.g., in the roots of a potato plant, trunk of a pine tree, leaves of tobacco and grain of wheat. Third, growth modulation by application of fertilizers and herbicides must be efficient to reduce costs and to protect the environment. As a result, effective control of plant growth traits is central to productive agriculture.

[0033] Plant growth is a complex trait subject to complex interactions of genes and the environment. Multiple genes, e.g., metabolic, structural and tissue specific genes, interact to influence plant growth. Multiple environmental factors, e.g., availability of nutrients, light conditions, temperature, the presence of herbicides, availability of water, the presence of salts, etc., also play roles in plant growth. Finally, the multiple genetic and environmental factors interact to provide the ultimate plant growth trait. Thus, identification of genes associated with growth in plants can furnish tools to investigate interactions that can produce a desired plant growth trait.

[0034] The present invention provides genes associated with plant growth, which are useful tools in deciphering the complex interactions for improved plant growth. The provided genes can be employed directly, e.g., to produce recombinant plants with desired characteristics. The polynucleotides and polypeptides of the invention can be used as tools, e.g., as elements of marker sets, sequence databases, probes, enzymes, and processes, to investigate interactions resulting in desired growth traits.

[0035] Definitions

[0036] Unless defined otherwise, all scientific and technical terms are understood to have the same meaning as commonly used in the art to which they pertain. For the purpose of the present invention, the following terms are defined below.

[0037] The term plant growth trait refers to quantifiable plant growth parameters such as, e.g., root length, aerial mass, root mass, total plant mass, stem growth rate, etc.

[0038] The term “nucleic acid” is generally used in its art-recognized meaning to refer to a ribose nucleic acid (RNA) or deoxyribose nucleic acid (DNA) polymer, or analog thereof, e.g., a nucleotide polymer comprising modifications of the nucleotides, a peptide nucleic acid, or the like. In certain applications, the nucleic acid can be a polymer that includes both RNA and DNA subunits. A nucleic acid can be, e.g., a chromosome or chromosomal segment, a vector (e.g., an expression vector), a naked DNA or RNA polymer, the product of a polymerase chain reaction (PCR), an oligonucleotide, a probe, etc.

[0039] The term “polynucleotide sequence” refers to a contiguous sequence of nucleotides in a single nucleic acid or to a representation, e.g., a character string, thereof. “Polymorphic polynucleotides” are polynucleotide sequences corresponding to a single locus, i.e., alleles at a locus, characterized by at least one variant (or alternative) nucleotide subunit. Thus, a polymorphic polynucleotide is a polynucleotide that differs, e.g., from another allele at the same locus, or between an otherwise homologous or similar polynucleotide, at one or more nucleotide positions.

[0040] A “phenotype” is the display of a trait in an individual organism resulting from the interaction of gene expression and the environment.

[0041] An “expression vector” is a vector, e.g., a plasmid, capable of producing transcripts and, potentially, polypeptides encoded by a polynucleotide sequence. Typically, an expression vector is capable of producing transcripts in an exogenous cell, e.g., a bacterial cell, or a plant cell, in vivo or invitro, e.g., a cultured plant protoplast. Expression of a product can be either constitutive or inducible depending, e.g., on the promoter selected. In the context of an expression vector, a promoter is said to be “operably linked” to a polynucleotide sequence if it is capable of regulating expression of the associated polynucleotide sequence. The term also applies to alternative exogenous gene constructs, such as expressed or integrated transgenes. Similarly, the term operably linked applies equally to alternative or additional transcriptional regulatory sequences such as enhancers, associated with a polynucleotide sequence.

[0042] An “expression product” is a transcribed sense or antisense RNA, or a translated polypeptide corresponding to a polynucleotide sequence. Depending on context, the term also can be used to refer to an amplification product (amplicon) or cDNA corresponding to the RNA expression product transcribed from the polynucleotide sequence.

[0043] A polynucleotide sequence is said to “encode” a sense or antisense RNA molecule, or a polypeptide, if the polynucleotide sequence can be transcribed (in spliced or unspliced form) or translated into the RNA or polypeptide, or a fragment of thereof.

[0044] A probe and a gene (or expression product) are said to “correspond” when they share substantial structural identity, or complimentarity, depending on context. For example, a probe or an expression product, e.g., a messenger RNA, corresponds to a gene when it is derived from a genetic element with substantial sequence identity.

[0045] Polynucleotides of the Invention

[0046] The present invention is based on the identification of nucleic acid sequences and full length genes associated with control of growth traits in plants. The gene sequences of the invention can influence plant growth by their presence in the genome of a plant species or by the abundance of their expression products in such a plant.

[0047] The sequences of the invention can be implicated in control of plant growth traits in their differential expression between plants with high growth and low growth characteristics. The specified sequences can be implicated in the control of growth traits in plants by their differential regulation in response to environmental factors known to induce or suppress display of the growth traits. Unlike the vast majority of polynucleotide sequences present in the plant genome, e.g., randomly selected unique or repetitive polynucleotide sequences, this defined and limited group of polynucleotides, possess an extraordinary high probability of association with loci involved in the growth traits in plants.

[0048] Given the sequences of the invention, as disclosed herein, those skilled in the art can readily synthesize the sequences or screen them from nature. Screening from nature can be, e.g., by massively parallel signature sequencing (MPSS). Massively parallel signature sequencing is a wide ranging and sensitive quantitative cDNA analysis tool for preparation of expression profiles, Brenner et al. “In vitro cloning of complex mixtures of DNA on microbeads: Physical separation of differentially expressed cDNAs”, (2000) PNAS 97, 1665-1670. In MPSS, cDNA is prepared from poly(A) RNA (mRNA) using a biotin-labeled oligo-dT primer. The oligo-dT is designed to prime each mRNA molecule exactly at the poly(A) junction. The cDNA fragments are then digested with DpnII (recognition sequence GATC), and the 3′-most DpnII-poly(A) fragments are purified utilizing the biotin label at the end of each molecule. The fragments are subsequently bound to 5 micron diameter microbeads using a complex set of 32 base tag/antitags. This process yields a library of beads where one mRNA molecule is represented by one microbead, and each microbead contains approximately 100,000 identical cDNA fragments from that mRNA. All molecules are covalently attached to the microbeads at their poly(A) ends; therefore, the DPNII end is available for sequencing reactions. Expression differences between organisms, e.g., of different phenotypes can be identified using MPSS as a tool.

[0049] Accordingly, in one aspect, the polynucleotide sequences of the invention are useful for identifying corresponding cDNAs associated with growth in plants and/or chromosomal segments associated with growth. More generally, the polynucleotide sequences of the invention and corresponding polypeptides are useful, individually and/or collectively, as probes (e.g., probes labeled with a detectable moiety) and markers. In addition, the polynucleotide sequences of the invention are useful for the production of plant and cell culture models useful for the monitoring of agents and evaluation of protocols aimed at controlling growth in plants. Nucleic acid sequences of the invention, e.g., SEQ ID NO: 1 through SEQ ID NO: 30, can also be used in vector systems to control plant growth, e.g., by transformation of plant cells to modulate expression of growth correlated genes.

[0050] Polynucleotide sequences of the invention include, e.g., the polynucleotide sequences represented by SEQ ID NO: 1 through SEQ ID NO: 30 and SEQ ID NO: 61 through SEQ ID NO: 403. In addition to the sequences expressly provided in the accompanying sequence listing, the invention includes polynucleotide sequences, that are highly related structurally and/or functionally. For example, polynucleotides encoding polypeptide sequences represented by SEQ ID NO: 31 through SEQ ID NO: 60, or subsequences thereof are one embodiment of the invention. In addition, polynucleotide sequences of the invention include polynucleotide sequences that hybridize under stringent conditions to a polynucleotide sequence comprising any of SEQ ID NO: 1-SEQ ID NO: 30.

[0051] In addition to the polynucleotide sequences of the invention, e.g., enumerated in SEQ ID NO: 1 to SEQ ID NO: 30, or SEQ ID NO: 61-SEQ ID NO: 403, polynucleotide sequences that are substantially identical to a polynucleotide of the invention can be used in the compositions and methods of the invention. Substantially identical or substantially similar polynucleotide (or polypeptide) sequences are defined as polynucleotide (or polypeptide) sequences that are identical, on a nucleotide by nucleotide bases, with at least a subsequence of a reference polynucleotide (or polypeptide), e.g., selected from SEQ ID NO: 1-30 (or 61-403). Such polynucleotides can include, e.g., insertions, deletions, and substitutions relative to any of SEQ ID NO: 1-30. For example, such polynucleotides are typically at least about 70% identical to a reference polynucleotide (or polypeptide) selected from among SEQ ID NO: 1 through SEQ ID NO: 30 (or 61-403). That is, at least 7 out of 10 nucleotides (or amino acids) within a window of comparison are identical to the reference sequence selected SEQ ID NO: 1-30. Frequently, such sequences are at least about 80%, usually at least about 90%, and often at least about 95%, or even at least about 98%, or about 99%, identical to the reference sequence, e.g., at least one of SEQ ID NO: 1 to SEQ ID NO: 30 or SEQ ID NO: 61 to SEQ ID NO: 403.

[0052] Subsequences of the polynucleotides of the invention described above, e.g., SEQ ID NOs: 1-30, including at least 10 contiguous nucleotides or complementary subsequences thereof are also a feature of the invention. More commonly a subsequence includes at least 12 contiguous nucleotides, e.g.;, of one or more of SEQ ID NO: 1 through SEQ ID NO: 30 or SEQ ID NO: 61 through SEQ ID NO: 403. Typically, the subsequence includes at least 14, frequently at least 16, and usually at least 17 or more contiguous nucleotides of one of the specified polynucleotide sequences. Such subsequences can be, e.g., oligonucleotides, such as synthetic oligonucleotides, or full-length genes or cDNAs.

[0053] In addition, polynucleotide sequences complementary to any of the above described sequences are included among the polynucleotides of the invention. Where the polynucleotide sequences are translated to form a polypeptide or subsequence of a polypeptide, the nucleotide changes can result in either conservative or non-conservative amino acid substitutions. Conservative amino acid substitutions refer to the interchangeability of residues having functionally similar side chains. Conservative substitution tables providing functionally similar amino acids are well known in the art. Table 1 sets forth six groups which contain amino acids that are “conservative substitutions” for one another. Other conservative substitution charts are available in the art, and can be used in a similar manner.

TABLE 1
Conservative Substitution Group
1	Alanine (A)	Serine (S)	Threonine (T)
2	Aspartic acid (D)	Glutamic acid (E)
3	Asparagine (N)	Glutamine (Q)
4	Arginine (R)	Lysine (K)
5	Isoleucine (I)	Leucine (L)	Methionine (M)	Valine (V)
6	Phenylalanine (F)	Tyrosine (Y)	Tryptophan (W)

[0054] One of skill in the art will appreciate that many conservative substitutions of the nucleic acid constructs which are disclosed yield a functionally identical construct. For example, as discussed above, owing to the degeneracy of the genetic code, “silent substitutions” (i.e., substitutions in a nucleic acid sequence which do not result in an alteration in an encoded polypeptide) are an implied feature of every nucleic acid sequence which encodes an amino acid. Similarly, “conservative amino acid substitutions,” in one or a few amino acids in an amino acid sequence (e.g., about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or more) are substituted with different amino acids with highly similar properties, are also readily identified as being highly similar to a disclosed construct. Such conservative variations of each disclosed sequence are a feature of the present invention.

[0055] Methods for obtaining conservative variants, as well as more divergent versions of the nucleic acids and polypeptides of the invention are widely known in the art. In addition to naturally occurring homologues which can be obtained, e.g., by screening genomic or expression libraries according to any of a variety of well-established protocols, see, e.g., Ausubel et al. Current Protocols in Molecular Biology (supplemented through 2001) John Wiley & Sons, New York (“Ausubel”); Sambrook et al. Molecular Cloning—A Laboratory Manual (2nd Ed.), Vol. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989 (“Sambrook”), and Berger and Kimmel Guide to Molecular Cloning Techniques, Methods in Enzymology volume 152 Academic Press, Inc., San Diego, Calif. (“Berger”), additional variants can be produced by a variety of mutagenesis procedures. Many such procedures are known in the art, including site directed mutagenesis, oligonucleotide-directed mutagenesis, and many others. For example, site directed mutagenesis is described, e.g., in Smith (1985) “In vitro mutagenesis” Ann. Rev. Genet. 19:423-462, and references therein, Botstein & Shortle (1985) “Strategies and applications of in vitro mutagenesis” Science 229:1193-1201; and Carter (1986) “Site-directed mutagenesis” Biochem. J. 237:1-7. Oligonucleotide-directed mutagenesis is described, e.g., in Zoller & Smith (1982) “Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any DNA fragment” Nucleic Acids Res. 10:6487-6500). Mutagenesis using modified bases is described e.g., in Kunkel (1985) “Rapid and efficient site-specific mutagenesis without phenotypic selection” Proc. Natl. Acad. Sci. USA 82:488-492, and Taylor et al. (1985) “The rapid generation of oligonucleotide-directed mutations at high frequency using phosphorothioate-modified DNA” Nucl. Acids Res. 13: 8765-8787. Mutagenesis using gapped duplex DNA is described, e.g., in Kramer et al. (1984) “The gapped duplex DNA approach to oligonucleotide-directed mutation construction” Nucl. Acids Res. 12: 9441-9460). Point mismatch repair is described, e.g., by Kramer et al. (1984) “Point Mismatch Repair” Cell 38:879-887). Double-strand break repair is described, e.g., in Mandecki (1986) “Oligonucleotide-directed double-strand break repair in plasmids of Escherichia coli: a method for site-specific mutagenesis” Proc. Natl. Acad. Sci. USA, 83:7177-7181, and in Arnold (1993) “Protein engineering for unusual environments” Current Opinion in Biotechnology 4:450-455). Mutagenesis using repair-deficient host strains is described, e.g., in Carter et al. (1985) “Improved oligonucleotide site-directed mutagenesis using M13 vectors” Nucl. Acids Res. 13: 4431-4443. Mutagenesis by total gene synthesis is described e.g., by Nambiar et al. (1984) “Total synthesis and cloning of a gene coding for the ribonuclease S protein” Science 223: 1299-1301. DNA shuffling is described, e.g., by Stemmer (1994) “Rapid evolution of a protein in vitro by DNA shuffling” Nature 370:389-391, and Stemmer (1994) “DNA shuffling by random fragmentation and reassembly: In vitro recombination for molecular evolution.” Proc. Natl. Acad. Sci. USA 91:10747-10751.

[0056] Many of the above methods are further described in Methods in Enzymology Volume 154, which also describes useful controls for trouble-shooting problems with various mutagenesis methods. Kits for mutagenesis, library construction and other diversity generation methods are also commercially available. For example, kits are available from, e.g., Amersham International plc (e.g., using the Eckstein method above), Anglian Biotechnology Ltd (e.g., using the Carter/Winter method above), Bio/Can Scientific, Bio-Rad (e.g., using the Kunkel method described above), Boehringer Mannheim Corp., Clonetech Laboratories, DNA Technologies, Epicentre Technologies (e.g., the 5 prime 3 prime kit); Genpak Inc, Lemargo Inc, Life Technologies (Gibco BRL), New England Biolabs, Pharmacia Biotech, Promega Corp., Quantum Biotechnologies, Stratagene (e.g., QuickChange™ site-directed mutagenesis kit; and Chameleon™ double-stranded, site-directed mutagenesis kit).

[0057] Determining Sequence Relationships

[0058] The nucleic acid and amino acid sequences of the invention include, e.g., those provided in SEQ ID NO: 1 to SEQ ID NO: 403 as well as similar sequences. Similar sequences are objectively determined by any number of methods, e.g., percent identity, hybridization, immunologically, and the like. A variety of methods for determining relationships between two or more sequences (e.g., identity, similarity and/or homology) are available, and well known in the art. The methods include manual alignment, computer assisted sequence alignment and combinations thereof. A number of algorithms (which are generally computer implemented) for performing sequence alignment are widely available, or can be produced by one of skill. These methods include, e.g., the local homology algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2:482; the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443; the search for similarity method of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. (USA) 85:2444; and/or by computerized implementations of these algorithms (e.g., GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package Release 7.0, Genetics Computer Group, 575 Science Dr., Madison, Wis.).

[0059] For example, software for performing sequence identity (and sequence similarity) analysis using the BLAST algorithm is described in Altschul et al. (1990) J. Mol. Biol. 215:403-410. This software is publicly available, e.g., through the National Center for Biotechnology Information on the world wide web at ncbi.nlm.nih.gov. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold. These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, a cutoff of 100, M=5, N=−4, and a comparison of both strands. For amino acid sequences, the BLASTP (BLAST Protein) program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see, Henikoff & Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915).

[0060] Additionally, the BLAST algorithm performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul (1993) Proc. Nat'l. Acad. Sci. USA 90:5873-5787). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (p(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence (and, therefore, in this context, homologous) if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, or less than about 0.01, and or even less than about 0.001.

[0061] Another example of a useful sequence alignment algorithm is PILEUP. PILEUP creates a multiple sequence alignment from a group of related sequences using progressive, pairwise alignments. It can also plot a tree showing the clustering relationships used to create the alignment. PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle (1987) J. Mol. Evol. 35:351-360. The method used is similar to the method described by Higgins & Sharp (1989) CABIOS5:151-153. The program can align, e.g., up to 300 sequences of a maximum length of 5,000 letters. The multiple alignment procedure begins with the pairwise alignment of the two most similar sequences, producing a cluster of two aligned sequences. This cluster can then be aligned to the next most related sequence or cluster of aligned sequences. Two clusters of sequences can be aligned by a simple extension of the pairwise alignment of two individual sequences. The final alignment is achieved by a series of progressive, pairwise alignments. The program can also be used to plot a dendogram or tree representation of clustering relationships. The program is run by designating specific sequences and their amino acid or nucleotide coordinates for regions of sequence comparison.

[0062] An additional example of an algorithm that is suitable for multiple DNA, or amino acid, sequence alignments is the CLUSTALW program (Thompson, J. D. et al. (1994) Nucl. Acids. Res. 22: 4673-4680). CLUSTALW performs multiple pairwise comparisons between groups of sequences and assembles them into a multiple alignment based on homology. Gap open and Gap extension penalties can be, e.g., 10 and 0.05 respectively. For amino acid alignments, the BLOSUM algorithm can be used as a protein weight matrix. See, e.g., Henikoff and Henikoff (1992) Proc. Natl. Acad. Sci. USA 89: 10915-10919.

[0063] Nucleic Acid Hybridization

[0064] Similarity between nucleic acids of the invention can also be evaluated by “hybridization” between single stranded (or single stranded regions of) nucleic acids with complementary or partially complementary polynucleotide sequences.

[0065] Hybridization is a measure of the physical association between nucleic acids, typically, in solution, or with one of the nucleic acid strands immobilized on a solid support, e.g., a membrane, a bead, a chip, a filter, etc. Nucleic acid hybridization occurs based on a variety of well characterized physico-chemical forces, such as hydrogen bonding, solvent exclusion, base stacking, and the like. Numerous protocols for nucleic acid hybridization are well known in the art. An extensive guide to the hybridization of nucleic acids is found in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology—Hybridization with Nucleic Acid Probes, part I, chapter 2, “Overview of principles of hybridization and the strategy of nucleic acid probe assays,” (Elsevier, New York), as well as in Ausubel et al. Current Protocols in Molecular Biology (supplemented through 2001) John Wiley & Sons, New York (“Ausubel”); Sambrook et al. Molecular Cloning—A Laboratory Manual (2nd Ed.), Vol. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989 (“Sambrook”), and Berger and Kimmel Guide to Molecular Cloning Techniques, Methods in Enzymology volume 152 Academic Press, Inc., San Diego, Calif. (“Berger”). Hames and Higgins (1995) Gene Probes 1, IRL Press at Oxford University Press, Oxford, England (Hames and Higgins 1) and Hames and Higgins (1995) Gene Probes 2, IRL Press at Oxford University Press, Oxford, England (Hames and Higgins 2) provide details on the synthesis, labeling, detection and quantification of DNA and RNA, including oligonucleotides.

[0066] Conditions suitable for obtaining hybridization, including differential hybridization, are selected according to the theoretical melting temperature (Tm) between complementary and partially complementary nucleic acids. Under a given set of conditions, e.g., solvent composition, ionic strength, etc., the Tm is the temperature at which the duplex between the hybridizing nucleic acid strands is 50% denatured. That is, the Tm corresponds to the temperature corresponding to the midpoint in transition from helix to random coil; it depends on the length of the nucleotides, nucleotide composition, and ionic strength, for long stretches of nucleotides.

[0067] After hybridization, unhybridized nucleic acids can be removed by a series of washes, the stringency of which can be adjusted depending upon the desired results. Low stringency washing conditions (e.g., using higher salt and lower temperature) increase sensitivity, but can product nonspecific hybridization signals and high background signals. Higher stringency conditions (e.g., using lower salt and higher temperature that is closer to the Tm) lower the background signal, typically with primarily the specific signal remaining. See, also, Rapley, R. and Walker, J. M. eds., Molecular Biomethods Handbook (Humana Press, Inc. 1998).

[0068] “Stringent hybridization wash conditions” or “stringent conditions” in the context of nucleic acid hybridization experiments, such as Southern and northern hybridizations, are sequence dependent, and are different under different environmental parameters. An extensive guide to the hybridization of nucleic acids is found in Tijssen (1993), supra, and in Hames and Higgins 1 and Hames and Higgins 2, supra.

[0069] An example of stringent hybridization conditions for hybridization of complementary nucleic acids which have more than 100 complementary residues on a filter in a Southern or northern blot is 2× SSC, 50% formamide at 42° C., with the hybridization being carried out overnight (e.g., for approximately 20 hours). An example of stringent wash conditions is a 0.2× SSC wash at 65° C. for 15 minutes (see Sambrook, supra for a description of SSC buffer). Often, the wash determining the stringency is preceded by a low stringency wash to remove signal due to residual unhybridized probe. An example low stringency wash is 2× SSC at room temperature (e.g., 20° C. for 15 minutes).

[0070] In general, a signal to noise ratio of at least 2.5×-5× (and typically higher) than that observed for an unrelated probe in the particular hybridization assay indicates detection of a specific hybridization. Detection of at least stringent hybridization between two sequences in the context of the present invention indicates relatively strong structural similarity to, e.g., the nucleic acids of the present invention provided in the sequence listings herein.

[0071] For purposes of the present invention, generally, “highly stringent” hybridization and wash conditions are selected to be about 5° C. or less lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH (as noted below, highly stringent conditions can also be referred to in comparative terms). Target sequences that are closely related or identical to the nucleotide sequence of interest (e.g., “probe”) can be identified under stringent or highly stringent conditions. Lower stringency conditions are appropriate for sequences that are less complementary.

[0072] For example, in determining stringent or highly stringent hybridization (or even more stringent hybridization) and wash conditions, the hybridization and wash conditions are gradually increased (e.g., by increasing temperature, decreasing salt concentration, increasing detergent concentration, and/or increasing the concentration of organic solvents, such as formamide, in the hybridization or wash), until a selected set of criteria are met. For example, the hybridization and wash conditions are gradually increased until a probe comprising one or more polynucleotide sequences of the invention, e.g., selected from SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 61 through SEQ ID NO: 403, and/or complementary polynucleotide sequences thereof, binds to a perfectly matched complementary target (again, a nucleic acid comprising one or more nucleic acid sequences or subsequences selected from SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 61 through SEQ ID NO: 403, and complementary polynucleotide sequences thereof), with a signal to noise ratio that is at least 2.5×, and optionally 5×, or 10×, or 100× or more, as high as that observed for hybridization of the probe to an unmatched target, as desired.

[0073] For example, using subsequences derived from the nucleic acids encoding the polypeptides of the invention, novel target nucleic acids can be obtained; such target nucleic acids are also a feature of the invention. For example, such target nucleic acids include sequences that hybridize under stringent conditions to an oligonucleotide probe that encodes a unique subsequence in any of the polypeptides of the invention, e.g., SEQ ID NOs: 31-60.

[0074] For example, hybridization conditions are chosen under which a target oligonucleotide that is perfectly complementary to the oligonucleotide probe hybridizes to the probe with at least about a 5-10× higher signal to noise ratio than for hybridization of the target oligonucleotide to a negative control non-complimentary nucleic acid.

[0075] Higher ratios of signal to noise can be achieved by increasing the stringency of the hybridization conditions such that ratios of about 15×, 20×, 30×, 50× or more are obtained. The particular signal will depend on the label used in the relevant assay, e.g., a fluorescent label, a calorimetric label, a radio active label, or the like.

[0076] Probes

[0077] Nucleic acids including one or more polynucleotide sequence of the invention are favorably used as probes for the detection of complimentary, corresponding, or related nucleic acids in a variety of contexts, such as the nucleic hybridization experiments discussed above. The probes can be either DNA or RNA molecules, such as restriction fragments of genomic or cloned DNA, cDNAs, amplification products, transcripts, and oligonucleotides, and can vary in length from oligonucleotides as short as about 10 nucleotides in length to chromosomal fragments or cDNAs in excess of one or more kilobases. For example, in some embodiments, a probe of the invention includes a polynucleotide sequence or subsequence selected from among SEQ ID NO: 1 to SEQ ID NO: 30, SEQ ID NO: 61 through SEQ ID NO: 403, or sequences complementary thereto. Alternatively, polynucleotide sequences that are variants of one of the above designated sequences can be used as probes. Most typically, such variants include one or a few nucleotide variations. For example, pairs (or sets) of oligonucleotides can be selected, in which the two (or more) polynucleotide sequences are conservative variations of each other, wherein one polynucleotide sequence corresponds identically to a first allele or allelic variant and the other(s) correspond identically to additional alleles or allelic variants. Such pairs of oligonucleotide probes are particularly useful, e.g., for allele specific hybridization experiments to detect polymorphic nucleotides. In other applications, probes are selected that are more divergent, that is, probes that are at least about 70% (or 80%, 90%, 95%, 98%, or 99%) identical are selected.

[0078] The probes of the invention, as exemplified by sequences derived from SEQ ID NO: 1 through SEQ ID NO: 30 and SEQ ID NO: 61 through SEQ ID NO: 403, can also be used to identify additional useful polynucleotide sequences according to procedures routine in the art. In one set of embodiments, one or more probes, as described above, are utilized to screen libraries of expression products or chromosomal segments (e.g. expression libraries or genomic libraries) to identify clones that include sequences identical to, or with significant sequence similarity to, one or more of SEQ ID NO: 1-30, i.e., allelic variants, homologues or orthologues. In turn, each of these identified sequences can be used to make probes, including pairs or sets of variant probes as described above. It will be understood that in addition to such physical methods as library screening, computer assisted bioinformatic approaches, e.g., BLAST and other sequence homology search algorithms, and the like, can also be used for identifying related polynucleotide sequences. Polynucleotide sequences identified in this manner are also a feature of the invention.

[0079] For example, oligonucleotide probes, most typically produced by well known synthetic methods, such as the solid phase phosphoramidite triester method described by Beaucage and Caruthers (1981) Tetrahedron Letts. 22(20):1859-1862, e.g., using an automated synthesizer, as described in Needham-VanDevanter et al. (1984) Nucleic Acids Res., 12:6159-6168. Oligonucleotides can also be custom made and ordered from a variety of commercial sources known to persons of skill. Purification of oligonucleotides, where necessary, is typically performed by either native acrylamide gel electrophoresis or by anion-exchange UPLC as described in Pearson and Regnier (1983) J. Chrom. 255:137-149. The sequence of the synthetic oligonucleotides can be verified using the chemical degradation method of Maxam and Gilbert (1980) in Grossman and Moldave (eds.) Academic Press, New York, Methods in Enzymology 65:499-560. Custom oligos can also easily be ordered from a variety of commercial sources known to persons of skill.

[0080] In addition, essentially any nucleic acid can be custom ordered from any of a variety of commercial sources, such as The Midland Certified Reagent Company (mcrc@oligos.com), The Great American Gene Company (http:Hlwww.genco.com), ExpressGen Inc. (www.expressgen.com), Operon Technologies Inc. (Alameda, Calif.) and many others. Similarly, peptides and antibodies can be custom ordered from any of a variety of sources, such as PeptidoGenic (pkim@ccnet.com), HTI Bio-products, inc. (http:/Iwww.htibio.com), BMA Biomedicals Ltd (U.K.), Bio.Synthesis, Inc., and many others.

[0081] As noted, in one embodiment, oligonucleotide probes of the invention include subsequences of SEQ ID NO: 1 through SEQ ID NO: 30, SEQ ID NO: 61 through SEQ ID NO: 403, and/or complementary sequences thereof, including e.g., at least 10 contiguous nucleotides in length. Commonly, the oligonucleotide probes are at least 12 contiguous nucleotides in length; usually, the oligonucleotides are at least 14 contiguous nucleotides in length; frequently, the oligonucleotides are at least 16 contiguous nucleotides in length, and in many cases the oligonucleotides are at least 17 or more contiguous nucleotides of at least one sequence selected from SEQ ID NO: 1 to SEQ ID NO: 30 or SEQ ID NO: 61 through SEQ ID NO: 403. In some cases, the oligonucleotide probes consist of a polynucleotide sequence selected from SEQ ID NO: 1 through SEQ ID NO: 30 or from SEQ ID NO: 61 through SEQ ID NO: 403.

[0082] In other circumstances, e.g., relating to functional attributes of cells or organisms expressing the polynucleotides and polypeptides of the invention, probes that are polypeptides, peptides, or antibodies are favorably utilized. For example, polypeptides, polypeptide fragments, and peptides corresponding to, or derived from SEQ ID NO: 31 to SEQ ID NO: 60, are favorably used to identify and isolate antibodies or other binding proteins, e.g., from phage display libraries, combinatorial libraries, polyclonal sera, and the like.

[0083] Antibodies specific for any one of SEQ ID NO: 31 to SEQ ID NO: 60 are likewise valuable as probes for evaluating expression products, e.g., from cells or tissues. In addition, antibodies are particularly suitable for evaluating expression of proteins corresponding to SEQ ID NOs: 31-60, in situ, in a cell, tissue or whole plant, e.g., a plant providing an experimental model for manipulation of growth traits. Antibodies can be directly labeled with a detectable reagent as described below, or detected indirectly by labeling of a secondary antibody specific for the heavy chain constant region (i.e., isotype) of the specific antibody. Additional details regarding production of specific antibodies are provided below in the section entitled “Antibodies.”

[0084] Labeling and Detecting Probes

[0085] Numerous methods are available for labeling and detection of the nucleic acid and polypeptide (or peptide or antibody) probes of the invention, these include: 1) fluorescence (using, e.g., fluorescein, Cy-5, rhodamine or other fluorescent tags); 2) isotopic methods, e.g., using end-labeling, nick translation, random priming, or PCR to incorporate radioactive isotopes into the probe polynucleotide/oligonucleotide; 3) chemifluorescence using alkaline phosphatase and the substrate AttoPhos (Amersham) or other substrates that produce fluorescent products; 4) chemiluminescence (using either horseradish peroxidase and/or alkaline phosphatase with substrates that produce photons as breakdown products, kits providing reagents and protocols are available from such commercial sources as Amersham, Boehringer-Mannheim, and Life Technologies/Gibco BRL); and, 5) colorimetric methods (again using both horseradish peroxidase and alkaline phosphatase with substrates that produce a colored precipitate, kits are available from Life Technologies/Gibco BRL, and Boehringer-Mannheim). Other methods for labeling and detection will be readily apparent to one skilled in the art.

[0086] More generally, a probe can be labeled with any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, chemical, or other available means. Useful labels in the present invention include spectral labels such as fluorescent dyes (e.g., fluorescein isothiocyanate, Texas red, rhodamine, and the like), radiolabels (e.g., 3H, 125I, 35S, 14C, 32P, 33P, etc.), enzymes (e.g., horse-radish peroxidase, alkaline phosphatase, etc.), spectral colorimetric labels such as colloidal gold, or colored glass or plastic (e.g. polystyrene, polypropylene, latex, etc.) beads. The label may be coupled directly or indirectly to a component of the detection assay (e.g., a probe, such as an oligonucleotide, isolated DNA, amplicon, restriction fragment, or the like) according to methods well known in the art. As indicated above, a wide variety of labels may be used, with the choice of label depending on sensitivity required, ease of conjugation with the compound, stability requirements, available instrumentation, and disposal provisions. In general, a detector which monitors a probe-target nucleic acid hybridization is adapted to the particular label which is used. Typical detectors include spectrophotometers, phototubes and photodiodes, microscopes, scintillation counters, cameras, film and the like, as well as combinations thereof. Examples of suitable detectors are widely available from a variety of commercial sources known to persons of skill. Commonly, an optical image of a substrate comprising a nucleic acid array with particular set of probes bound to the array is digitized for subsequent computer analysis.

[0087] Because incorporation of radiolabeled nucleotides into nucleic acids is straightforward, this detection represents one favorable labeling strategy. Exemplar technologies for incorporating radiolabels include end-labeling with a kinase or phoshpatase enzyme, nick translation, incorporation of radio-active nucleotides with a polymerase and many other well known strategies.

[0088] Fluorescent labels are desirable, having the advantage of requiring fewer precautions in handling, and being amenable to high-throughput visualization techniques. Preferred labels are typically characterized by one or more of the following: high sensitivity, high stability, low background, low environmental sensitivity and high specificity in labeling. Fluorescent moieties, which are incorporated into the labels of the invention, are generally are known, including Texas red, fluorescein isothiocyanate, rhodamine, etc. Many fluorescent tags are commercially available from SIGMA chemical company (Saint Louis, Mo.), Molecular Probes (Eugene, Oreg.), R&D systems (Minneapolis, Minn.), Pharmacia LKB Biotechnology (Piscataway, N.J.), CLONTECH Laboratories, Inc. (Palo Alto, Calif.), Chem Genes Corp., Aldrich Chemical Company (Milwaukee, Wis.), Glen Research, Inc., GIBCO BRL Life Technologies, Inc. (Gaithersberg, Md.), Fluka Chemica-Biochemika Analytika (Fluka Chemie AG, Buchs, Switzerland), and Applied Biosystems (Foster City, Calif.) as well as other commercial sources known to one of skill. Similarly, moieties such as digoxygenin and biotin, which are not themselves fluorescent but are readily used in conjunction with secondary reagents, i.e., anti-digoxygenin antibodies, avidin (or streptavidin), that can be labeled, are suitable as labeling reagents in the context of the probes of the invention.

[0089] The label is coupled directly or indirectly to a molecule to be detected (a product, substrate, enzyme, or the like) according to methods well known in the art. As indicated above, a wide variety of labels are used, with the choice of label depending on the sensitivity required, ease of conjugation of the compound, stability requirements, available instrumentation, and disposal provisions. Non-radioactive labels are often attached by indirect means. Generally, a ligand molecule (e.g., biotin) is covalently bound to a nucleic acid such as a probe, primer, amplicon, or the like. The ligand then binds to an anti-ligand (e.g., streptavidin) molecule which is either inherently detectable or covalently bound to a signal system, such as a detectable enzyme, a fluorescent compound, or a chemiluminescent compound. A number of ligands and anti-ligands can be used. Where a ligand has a natural anti-ligand, for example, biotin, thyroxine, and cortisol, it can be used in conjunction with labeled, anti-ligands. Alternatively, any haptenic or antigenic compound can be used in combination with an antibody. Labels can also be conjugated directly to signal generating compounds, e.g., by conjugation with an enzyme or fluorophore or chromophore. Enzymes of interest a labels will primarily be hydrolases, particularly phosphatases, esterases and glycosidases, or oxidoreductases, particularly peroxidases. Fluorescent compounds include fluorescein and its derivatives, rhodamine and its derivatives, dansyl, umbelliferone, etc. Chemiluminescent compounds include luciferin, and 2,3-dihydrophthalazinediones, e.g., luminol. Means of detecting labels are well known to those of skill in the art. Thus, for example, where the label is a radioactive label, means for detection include a scintillation counter or photographic film as in autoradiography. Where the label is optically detectable, typical detectors include microscopes, cameras, phototubes and photodiodes and many other detection systems which are widely available.

[0090] It will be appreciated that probe design is influenced by the intended application. For example, where several allele-specific probe-target interactions are to be detected in a single assay, e.g., on a single DNA chip, it is desirable to have similar melting temperatures for all of the probes. Accordingly, the length of the probes are adjusted so that the melting temperatures for all of the probes on the array are closely similar (it will be appreciated that different lengths for different probes may be needed to achieve a particular Tm where different probes have different GC contents). Although melting temperature is a primary consideration in probe design, other factors are optionally used to further adjust probe construction, such as selecting against primer self-complementarity and the like.

[0091] Marker Sets

[0092] Sets of probes, including multiple nucleic acids with polynucleotide sequences or sequences selected from among the polynucleotides of the invention, e.g., SEQ ID NO: 1 through SEQ ID NO: 30, SEQ ID NO: 61 through SEQ ID NO: 403, or subsequences thereof, or conservative variants thereof, or sequences complimentary to any of the foregoing are also a feature of the invention. Such sets of probes are useful as marker sets, e.g., for predicting plant growth traits before they become apparent, identifying plant or cell phenotype, and/or the like.

[0093] Marker sets of the invention favorably include any of the probe sequences described above, such as polynucleotide sequences that hybridize under stringent conditions to any one of SEQ ID NO: 1-SEQ ID NO: 30, any one of SEQ ID NO: 61 through SEQ ID NO: 403, sequences that are at least 70% identical to any one of SEQ ID NO: 1-SEQ ID NO: 30, sequences that encode a polypeptide or peptide comprising a subsequence encoded by any one of SEQ ID NO: 31-SEQ ID NO: 60, sequences complementary to any such sequences, or subsequences thereof.

[0094] In one embodiment, the marker set of the invention is a plurality of oligonucleotides, e.g., synthetic oligonucleotides produced by the phosporamidite triester synthesis method on an automated synthesizer, as described above. For example, at least two oligonucleotides including a polynucleotide sequence of at least 10 contiguous nucleotides of sequences selected from a polynucleotide of the invention, e.g., SEQ ID NO: 1 to SEQ ID NO: 30 or SEQ ID NO: 61 through SEQ ID NO: 403, can be used as a set to predict plant growth traits before they become apparent. Frequently, the oligonucleotides selected will be longer than 10 contiguous nucleotides in length, for example, oligonucleotides of at least 12, or 14, or 16 or 17, or more contiguous nucleotides are favorably employed in the marker sets of the invention.

[0095] While as few as one or two probes can constitute a marker set, it is frequently desirable to employ marker sets with more than two members. Typically, a marker set of the invention has at least 3, often at least about 5 or more members selected from among any of the polynucleotides of the invention. In one favorable embodiment, the marker set includes oligonucleotides corresponding in sequence to at least part of each of SEQ ID NO: 1 through SEQ ID NO: 30 or SEQ ID NO: 61 through SEQ ID NO: 403. In another embodiment, the marker sets are made up of expression products such as cDNAs, or amplification products corresponding to cDNA or RNA expression products.

[0096] In some applications, the marker set includes labeled nucleic acid probes as described in the preceding section. In other applications, e.g., certain array applications, a labeled nucleic acid sample is hybridized to a set of unlabeled marker nucleic acids.

[0097] The marker sets of the invention are frequently employed in the context of a polynucleotide sequence array. Any of the polynucleotide sequences of the invention, as described above, can be logically or physically arrayed to produce a useful array. For example, nucleic acids, e.g., oligonucleotides, cDNAs, amplicons, and/or chromosomal segments, can be physically arrayed in a solid phase or liquid phase array. Common solid phase arrays include a variety of solid substrates suitable for attaching nucleic acids in an ordered manner, such as membranes, filters, chips, beads, pins, slides, plates, etc. Common liquid phase arrays include, e.g., arrays of wells (e.g., as in microtiter trays) or containers (e.g., as in arrays of test tubes).

[0098] Nucleic acids of the marker sets are optionally immobilized, for example by direct or indirect cross-linking, to the solid support. Essentially any solid support capable of withstanding the reagents and conditions used in the particular detection assay can be utilized. For example, functionalized glass, silicon, silicon dioxide, modified silicon, any of a variety of polymers, such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, polycarbonate, membranes (e.g., nylon or nitrocellulose), or combinations thereof, can all serve as the substrate for a solid phase array.

[0099] In one embodiment, the array is a “chip” composed, e.g., of one of the above specified materials. Polynucleotide probes, e.g., RNA or DNA, such as cDNA, synthetic oligonucleotides, and the like, as discussed above are adhered to the chip in a logically ordered manner, i.e., in an array. Additional details regarding methods for linking nucleic acids and proteins to a chip substrate, can be found in, e.g., U.S. Pat. No. 5,143,854 “Large Scale Photolithographic Solid Phase Synthesis of Polypeptides and Receptor Binding Screening Thereof” to Pirrung et al., issued, Sep. 1, 1992; U.S. Pat. No. 5,837,832 “Arrays of Nucleic Acid Probes on Biological Chips” to Chee et al., issued Nov. 17, 1998; U.S. Pat. No. 6,087,112 “Arrays with Modified Oligonucleotide and Polynucleotide Compositions” to Dale, issued Jul. 11, 2000; U.S. Pat. No. 5,215,882 “Method of Immobilizing Nucleic Acid on a Solid Substrate for Use in Nucleic Acid Hybridization Assays” to Bahl et al., issued Jun. 1, 1993; U.S. Pat. No. 5,707,807 “Molecular Indexing for Expressed Gene Analysis” to Kato, issued Jan. 13, 1998; U.S. Pat. No. 5,807,522 “Methods for Fabricating Microarrays of Biological Samples” to Brown et al., issued Sep. 15, 1998; U.S. Pat. No. 5,958,342 “Jet Droplet Device” to Gamble et al., issued Sep. 28, 1999; U.S. Pat. No. 5,994,076 “Methods of Assaying Differential Expression” to Chenchik et al., issued Nov. 30, 1999; U.S. Pat. No. 6,004,755 “Quantitative Microarray Hybridization Assays” to Wang, issued Dec. 21, 1999; U.S. Pat. No. 6,048,695 “Chemically Modified Nucleic Acids and Method for Coupling Nucleic Acids to Solid Support” to Bradley et al., issued Apr. 11, 2000; U.S. Pat. No. 6,060,240 “Methods for Measuring Relative Amounts of Nucleic Acids in a Complex Mixture and Retrieval of Specific Sequences Therefrom” to Kamb et al., issued May 9, 2000; U.S. Pat. No. 6,090,556 “Method for Quantitatively Determining the Expression of a Gene” to Kato, issued Jul. 18, 2000; and U.S. Pat. No. 6,040,138 “Expression Monitoring by Hybridization to High Density Oligonucleotide Arrays” to Lockhart et al., issued Mar. 21, 2000.

[0100] In addition to being able to design, build and use probe arrays using available techniques, one of skill can simply order custom-made arrays and array-reading devices from manufacturers specializing in array manufacture. For example, custom arrays are available through Agilent Technology, Inc. or through Affymetrix Corp., in Santa Clara, Calif. which manufactures DNA VLSIP™ arrays.

[0101] In addition to marker sets made up of nucleic acid probes described above, marker sets including polypeptide, peptide, and antibody probes as discussed in the section entitled “Labeled Probes” are favorably used in certain applications. As discussed above for individual probes, sets of probes including multiple members selected from SEQ ID NOs: 31-60, or antibodies specific to such sequences can be used in liquid phase, or immobilized as described above with respect to nucleic acid markers.

[0102] Vectors, Promoters and Expression Systems

[0103] The present invention includes recombinant constructs incorporating one or more of the nucleic acid sequences described above. Such constructs include a vector, for example, a plasmid, a cosmid, a phage, a virus, a bacterial artificial chromosome (BAC), a yeast artificial chromosome (YAC), etc., into which one or more of the polynucleotide sequences of the invention, e.g., comprising any of SEQ ID NO: 1-30 or SEQ ID NO: 61-403, or a subsequence thereof, has been inserted, in a forward or reverse orientation. For example, the inserted nucleic acid can include a chromosomal sequence or cDNA including a all or part of at least one of SEQ ID NO: 1 through SEQ ID NO: 30, such as a sequence originating on Arabidopsis chromosome 2, or a cDNA corresponding to an mRNA expression product transcribed from a polynucleotide sequence on Arabidopsis chromosome 2. In an embodiment, the construct further comprises regulatory sequences, including, for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available.

[0104] The polynucleotides of the present invention can be included in any one of a variety of vectors suitable for generating sense or antisense RNA, and optionally, polypeptide expression products. Such vectors include chromosomal, nonchromosomal and synthetic DNA sequences, e.g., derivatives of SV40; bacterial plasmids; phage DNA; baculovirus; yeast plasmids; vectors derived from combinations of plasmids and phage DNA, viral DNA such as vaccinia, adenovirus, fowl pox virus, pseudorabies, adenovirus, adeno-associated virus, retroviruses and many others. Any vector that is capable of introducing genetic material into a cell, and, if replication is desired, which is replicable in the relevant host can be used.

[0105] In an expression vector, the polynucleotide sequence of interest is physically arranged in proximity and orientation to an appropriate transcription control sequence (promoter, and optionally, one or more enhancers) to direct mRNA synthesis. That is, the polynucleotide sequence of interest is operably linked to an appropriate transcription control sequence. Examples of such promoters include: LTR or SV40 promoter, E. coli lac or trp promoter, phage lambda PL promoter, and other promoters known to control expression of genes in prokaryotic or eukaryotic cells or their viruses. The expression vector also contains a ribosome binding site for translation initiation, and a transcription terminator. The vector optionally includes appropriate sequences for amplifying expression.

[0106] For example, constitutive promoters useful in vectors of the invention include the cauliflower mosaic virus (CaMV) 35S transcription initiation region, the 1′- or 2′-promoter derived from T-DNA of Agrobacterium tumefaciens, and other transcription initiation regions from various bacterial, plant or animal genes known to those of skill. Alternatively, the promoter can direct expression of a polynucleotide of the invention in a specific tissue (tissue-specific promoters) or can be otherwise under more precise environmental control (inducible promoters). Examples of tissue-specific promoters under developmental control include promoters that initiate transcription only in certain tissues, such as fruit, seeds, or flowers.

[0107] Any of a number of promoters which direct transcription in cells can be suitable. The promoter can be either constitutive or inducible. For example, in addition to the promoters noted above, promoters of bacterial origin which operate in plants include the octopine synthase promoter, the nopaline synthase promoter and other promoters derived from native Ti plasmids. See, Herrara-Estrella et al. (1983), Nature, 303:209-213. Viral promoters include the 35S and 19S RNA promoters of cauliflower mosaic virus. See, Odell et al. (1985) Nature, 313:810-812. Other plant promoters include the ribulose-1,3-bisphosphate carboxylase small subunit promoter and the phaseolin promoter. The promoter sequence from the E8 gene and other genes can also be used. The isolation and sequence of the E8 promoter is described in detail in Deikman and Fischer, (1988) EMBO J. 7:3315-3327. Many other promoters are in current use and can be coupled to an exogenous DNA sequence to direct expression of the nucleic acid.

[0108] In addition, the expression vectors optionally comprise one or more selectable marker genes to provide a phenotypic trait for selection of transformed host cells, such as dihydrofolate reductase or neomycin resistance for eukaryotic cell culture, or such as tetracycline or ampicillin resistance in E. coli. The vector comprising the sequences (e.g., promoters or coding regions) from genes encoding expression products and polynucleotides of the invention optionally include a nucleic acid subsequence, a marker gene which confers a selectable, or alternatively, a screenable, phenotype on plant cells. For example, the marker may encode biocide tolerance, particularly antibiotic tolerance, such as tolerance to kanamycin, G418, bleomycin, hygromycin, or in plants: herbicide tolerance, such as tolerance to chlorosluforon, or phosphinothricin (the active ingredient in the herbicides bialaphos or Basta). See, e.g., Padgette et al. (1996) “New weed control opportunities: Development of soybeans with a Round UP Ready™ gene” In: Herbicide-Resistant Crops (Duke, ed.), pp. 53-84, CRC Lewis Publishers, Boca Raton (“Padgette, 1996”). For example, crop selectivity to specific herbicides can be conferred by engineering genes into crops which encode appropriate herbicide metabolizing enzymes from other organisms, such as microbes. See, Vasil (1996) “Phosphinothricin-resistant crops” In: Herbicide-Resistant Crops (Duke, ed.), pp 85-91, CRC Lewis Publishers, Boca Raton) (“Vasil”, 1996).

[0109] Additional Expression Elements

[0110] Where translation of polypeptide encoded by a nucleic acid comprising a polynucleotide sequence of the invention is desired, additional translation specific initiation signals can improve the efficiency of translation. These signals can include, e.g., an ATG initiation codon and adjacent sequences. In some cases, for example, full-length cDNA molecules or chromosomal segments including a coding sequence incorporating, e.g., a polynucleotide sequence of the invention, a translation initiation codon and associated sequence elements are inserted into the appropriate expression vector simultaneously with the polynucleotide sequence of interest. In such cases, additional translational control signals frequently are not required. However, in cases where only a polypeptide coding sequence, or a portion thereof, is inserted, exogenous translational control signals, including an ATG initiation codon is provided for expression of the relevant sequence. The initiation codon is put in the correct reading frame to ensure transcription of the polynucleotide sequence of interest. Exogenous transcriptional elements and initiation codons can be of various origins, both natural and synthetic. The efficiency of expression can be enhanced by the inclusion of enhancers appropriate to the cell system in use (Scharf D et al. (1994) Results Probl Cell Differ 20:125-62; Bittner et al. (1987) Methods in Enzymol 153:516-544).

[0111] Expression Hosts

[0112] The present invention also relates to host cells which are transduced with vectors of the invention, and the production of polypeptides of the invention by recombinant techniques. Host cells are genetically engineered (i.e., transduced, transformed or transfected) with a vector, such as an expression vector, of this invention. As described above, the vector can be in the form of a plasmid, a viral particle, a phage, etc. Examples of appropriate expression hosts include: bacterial cells, such as Agrobacterium tumefaciens, E. coli, Streptomyces, and Salmonella typhimurium; fungal cells, such as Saccharomyces cerevisiae, Pichia pastoris, and Neurospora crassa; insect cells such as Drosophila and Spodoptera frugiperda; mammalian cells such as COS, CHO, BHK, HEK 293 or Bowes melanoma; plant cells, etc.

[0113] The engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants, or amplifying the inserted polynucleotide sequences. The culture conditions, such as temperature, pH and the like, are typically those previously used with the host cell selected for expression, and will be apparent to those skilled in the art and in the references cited herein, including, e.g., Freshney (1994) Culture of Animal Cells, a Manual of Basic Technique, third edition, Wiley-Liss, New York and the references cited therein. Expression products corresponding to the nucleic acids of the invention can also be produced in non-animal cells such as plants, yeast, fungi, bacteria and the like. In addition to Sambrook, Berger and Ausubel, details regarding cell culture can be found in Payne et al. (1992) Plant Cell and Tissue Culture in Liquid Systems John Wiley & Sons, Inc. New York, N.Y.; Gamborg and Phillips (eds) (1995) Plant Cell, Tissue and Organ Culture; Fundamental Methods Springer Lab Manual, Springer-Verlag (Berlin Heidelberg New York) and Atlas and Parks (eds) The Handbook of Microbiological Media (1993) CRC Press, Boca Raton, Fla.

[0114] In bacterial systems, a number of expression vectors can be selected depending upon the use intended for the expressed product. For example, when large quantities of a polypeptide or fragments thereof are needed for the production of antibodies, vectors which direct high level expression of fusion proteins that are readily purified are favorably employed. Such vectors include, but are not limited to, multifunctional E. coli cloning and expression vectors such as BLUESCRIPT (Stratagene), in which the coding sequence of interest, e.g., a polynucleotide of the invention as described above, can be ligated into the vector in-frame with sequences for the amino-terminal translation initiating Methionine and the subsequent 7 residues of beta-galactosidase producing a catalytically active beta galactosidase fusion protein; pIN vectors (Van Heeke & Schuster (1989) J Biol Chem 264:5503-5509); pET vectors (Novagen, Madison Wis.); and the like.

[0115] Similarly, in the yeast Saccharomyces cerevisiae a number of vectors containing constitutive or inducible promoters such as alpha factor, alcohol oxidase and PGH can be used for production of the desired expression products. For reviews, see Berger, Ausubel, and, e.g., Grant et al. (1987; Methods in Enzymology 153:516-544).

[0116] In mammalian host cells, a number expression systems, such as viral-based systems, can be utilized. For example, in cases where an adenovirus is used as an expression vector, a coding sequence is optionally ligated into an adenovirus transcription/translation complex consisting of the late promoter and tripartite leader sequence. Insertion in a nonessential E1 or E3 region of the viral genome will result in a viable virus capable of expressing the polypeptides of interest in infected host cells (Logan and Shenk (1984) Proc Natl Acad Sci 81:3655-3659). In addition, transcription enhancers, such as the rous sarcoma virus (RSV) enhancer, can be used to increase expression in mammalian host cells.

[0117] Transformed or transfected host cells containing the expression vectors described above are also a feature of the invention. The host cell can be a eukaryotic cell, such as a mammalian cell, a yeast cell, or a plant cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-Dextran mediated transfection, electroporation, or other common techniques (Davis, L., Dibner, M., and Battey, I. (1986) Basic Methods in Molecular Biology).

[0118] A host cell strain is optionally chosen for its ability to modulate the expression of the inserted sequences or to process the expressed protein in the desired fashion. Such modifications of the protein include, but are not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation, and acylation. Post-translational processing which cleaves a precursor form into a mature form of the protein is sometimes important for correct insertion, folding, and/or function. Different host cells such as bacterial, fungal, plant and animal host cells have specific cellular machinery and characteristic mechanisms for such post-translational activities and can be chosen to ensure the correct modification and processing of the introduced, foreign protein.

[0119] For long-term, high-yield production of recombinant proteins encoded by or having subsequences encoded by the polynucleotides of the invention, stable expression systems are typically used. For example, cell lines which stably express a polypeptide of the invention are transfected using expression vectors which contain viral origins of replication or endogenous expression elements and a selectable marker gene. Following the introduction of the vector, cells are allowed to grow for 1-2 days in an enriched media before they are switched to selective media. The purpose of the selectable marker is to confer resistance to selection, and its presence allows growth and recovery of cells which successfully express the introduced sequences. For example, resistant colonies of stably transformed cells can be proliferated using tissue culture techniques appropriate to the cell type.

[0120] Host cells transformed with a nucleotide sequence encoding a polypeptide of the invention are optionally cultured under conditions suitable for the expression and recovery of the encoded protein from cell culture. The protein or fragment thereof produced by a recombinant cell can be secreted, membrane-bound, or contained intracellularly, depending on the sequence and/or the vector used.

[0121] Plant Transformation

[0122] The nucleic acids of the invention can be introduced into plants to modulate growth of the plants. That is, expression of the nucleic acids, e.g., when present as transgenes can modulate growth of the plants. Similarly, transgenic expression of sense or anti-sense sequences of the invention can modulate expression of endogenous forms or homologues of the nucleic acids, thereby modulating growth of the plants. Thus, the sequences specified herein, or homologues (or other variants) thereof, can be expressed to modulate plant growth.

[0123] The nucleic acids of the invention are optionally expressed under the control of an inducible promoter, e.g., a promoter regulated by an environmental signal (e.g., a chemical, a hormone (e.g., a plant or insect hormone), heat, light, water or the like. Alternately, a constitutive promoter can be used to drive expression of a nucleic acid of interest.

[0124] It can also be useful to stack expression of multiple nucleic acids of the invention in a single plant to modulate growth of the plant, or to stack expression of the nucleic acids of the invention with any other nucleic acid that provides a desired property (resistance to pests, herbicides, etc).

[0125] As noted, natural homologues, e.g., of the Arabadopsis sequences noted herein can be identified using standard molecular techniques as noted herein, and/or using sequence comparison methods as noted herein. In one embodiment, nucleic acids corresponding to homologues from a species are introduced as components of expression vectors into plants of that species (e.g., a corn homologue is introduced into corn) to modulate plant growth of the resulting transgenic plant. In another embodiment, nucleic acids from a species are introduced into a different species (e.g., a corn homologue is optionally introduced into a different grass family plant) to modulate plant growth of the resulting transgenic plant.

[0126] Accordingly, polynucleotides of the invention can be introduced into an Arabidopsis or any other desired plant genome, e.g., Brassica, Zea, Oryza, Triticum, Hordeum, Lolium, Sorghum, Glycine, Medicago, Helianthus, Lactuca, Beta, Vitis, Solanum, Lycopersicon, Capsicum, Gossypium, Hevea, Linum, Prunus, Citrus, Populus, Pinus, and Quercus, using a number of techniques well established in the art. Methods for transforming a wide variety of higher plant species have been described in the technical and scientific literature (see, e.g., Payne et al. (1992) Plant Cell and Tisue Culture in Liquid Systems John Wiley & Sons, Inc. New York, N.Y.; Gamborg and Phillips (1995) Plant Cell, Tissue and Organ Culture: Fundamental Methods Springer Lab Manual, Springer-Verlag, Berlin; Jones (1995) Plant Gene Transfer and Expression Protocols: Methods in Molecular Biology, Volume 49 Humana Press, Towata, N.J.; and Croy (1993) Plant Molecular Biology Bios Scientific Publishers, Oxfore, U.K., as well as, e.g., Weising et al. (1988) Ann. Rev. Genet. 22:421.

[0127] In many cases, introduction of exogenous nucleic acids into a plant genome is facilitated by molecular transformation of plant protoplasts or isolated plant tissues in a tissue culture system, e.g., a liquid tissue culture system, as described in the references above. Numerous protocols for establishment of transformable protoplasts from a variety of plant types and subsequent transformation of the cultured protoplasts are available in the art and are incorporated herein by reference. For examples, see, Hashimoto et al. (1990) Plant Physiol. 93:857; Fowke and Constabel (eds)(1994) Plant Protoplasts; Saunders et al. (1993) Applications of Plant In Vitro Technology Symposium, UPM 16-18; and Lyznik et al. (1991) BioTechniques 10:295, each of which is incorporated herein by reference.

[0128] Nucleic acids, e.g., DNA expression vectors comprising the polynucleotides of the invention, can be introduced directly into the genomic DNA of a plant cell using techniques such as electroporation (see, e.g., Fromm et al. (1985) Proc Nat'l Acad Sci USA 82:5824), polyethylene glycol precipitation (see, e.g., Paszkowski et al. (1984) EMBO J. 3:2717) and microinjection of plant cell protoplasts. Ballistic methods, such as DNA particle bombardment can be used to introduce DNA into plant tissues (see, e.g., Klein et al. (1987) Nature 327:70; and Weeks et al. Plant Physiol 102:1077).

[0129] Alternatively, the polynucleotides of the invention can be combined with suitable T-DNA flanking regions and introduced into a conventional Agrobacterium tumefaciens host vector. Agrobacterium-mediated transformation is widely used for the transformation of dicots, such as Arabidopsis as well as numerous other species of experimental and commercial interest, as well as certain monocots. For example, Agrobacterium transformation of rice is described by Hiei et al. (1994) Plant J. 6:271; U.S. Pat. No. 5,187,073; U.S. Pat. No. 5,591,616; Li et al. (1991) Science in China 34:54; and Raineri et al. (1990) Bio/Technology 8:33. Transformed maize, barley, triticale and asparagus by Agrobacterium mediated transformation have also been described (Xu et al. (1990) Chinese J Bot 2:81).

[0130] Agrobacterium mediated transformation techniques take advantage of the ability of the tumor-inducing (Ti) plasmid of A. tumefaciens to integrate into a plant cell genome, to co-transfer a nucleic acid of interest into a plant cell. Typically, an expression vector is produced wherein the nucleic acid of interest, such as a GAT polynucleotide of the invention, is ligated into an autonomously replicating plasmid which also contains T-DNA sequences. T-DNA sequences typically flank the expression cassette nucleic acid of interest and comprise the integration sequences of the plasmid. In addition to the expression cassette, T-DNA also typically includes a marker sequence, e.g., antibiotic resistance genes. The plasmid with the T-DNA and the expression cassette can then be transfected into Agrobacterium cells. Typically, for effective transformation of plant cells, the A. tumefaciens bacterium also possesses the necessary vir regions on a plasmid, or integrated into its chromosome. For a discussion of Agrobacterium mediated transformation, see, Firoozabady and Kuehnle, (1995) Plant Cell Tissue and Organ Culture Fundamental Methods, Gamborg and Phillips (eds.).

[0131] In addition, methods for transforming Arabidopsis in whole plants without tissue culture have been developed, e.g., using vacuum infiltration (Bechtold et al. (1993) “In planta Agrobacterium mediated gene transfer by infiltration of adult Arabidopsis thaliana plants”. CR Acad Sci Paris Life Sci 316:1194-1199) and simple dipping of flowering plants (Desfeux et al. (2000) “Female reproductive tissues are the primary target of Agrobacterium-mediated transformation by the Arabidopsis floral-dip method” Plant Physiol. 123:895-904).

[0132] Plant viral vectors can also be used to introduce exogenous nucleic acids comprising the polynucleotides of the invention into a plant genome. Typically, viral vectors are used when transient expression of the exogenous polynucleotide sequence is desirable. Viral vectors are simple to manipulate in vitro and can be easily introduced into mechanically wounded leaves of intact plants of a variety of laboratory plant species as well as common crop species. Over six-hundred-fifty plant viruses have been identified, and both DNA and RNA viruses have been used as vectors for gene replacement, gene insertion, epitope presentation and complementation, (see, e.g., Scholthof, Scholthof and Jackson, (1996) “Plant virus gene vectors for transient expression of foreign proteins in plants,” Annu. Rev. of Phytopathol. 34:299-323). The nucleotide sequences encoding many of these proteins are matters of public knowledge, and accessible through any of a number of databases, e.g. (Genbank: available at the world wide web at ncbi.nlm.nih.gov/genbank/or EMBL: available at the world wide web at ebi.ac.uk.embl/).

[0133] Methods for the transformation of plants and plant cells using sequences derived from plant viruses include the direct transformation techniques described above relating to DNA molecules, see e.g., Jones, ed. (1995) Plant Gene Transfer and Expression Protocols, Humana Press, Totowa, N.J., for a recent compilation. In addition viral sequences can be cloned adjacent T-DNA border sequences and introduced via Agrobacterium mediated transformation, or Agroinfection.

[0134] Viral particles comprising the plant virus vectors of the invention can also be introduced by mechanical inoculation using techniques well known in the art, (see e.g., Cunningham and Porter, eds. (1997) Methods in Biotechnology, Vol. 3. Recombinant Proteins from Plants: Production and Isolation of Clinically Useful Compounds, for detailed protocols).

[0135] Regeneration of Transgenic Plants

[0136] Transgenic plant cells which are derived by plant transformation techniques, including those discussed above, can be cultured to regenerate a whole plant which possesses the transformed genotype (e.g., SEQ ID NO: 1-30), and thus the desired phenotype, such as a desirable growth trait. Such regeneration techniques rely on manipulation of certain phytohormones in a tissue culture growth medium, typically relying on a biocide and/or herbicide marker which has been introduced together with the desired nucleotide sequences. Plant regeneration from cultured protoplasts is described in Evans et al. (1983) Protoplasts Isolation and Culture, Handbook of Plant Cell Culture, pp 124-176, Macmillan Publishing Company, New York; and Binding (1985) Regeneration of Plants, Plant Protoplasts pp 21-73, CRC Press, Boca Raton. Regeneration can also be obtained from plant callus, explants, organs, or parts thereof. Such regeneration techniques are described generally in Klee et al. (1987) Ann Rev of Plant Phys 38:467. See also, e.g., Payne and Gamborg, supra. After transformation with Agrobacterium, the explants typically are transferred to selection medium. One of skill will realize that the selection medium depends on the selectable marker that was co-transfected into the explants. After a suitable length of time, transformants will begin to form shoots. After the shoots are about 1-2 cm in length, the shoots should be transferred to a suitable root and shoot medium. Selection pressure should be maintained in the root and shoot medium.

[0137] Typically, the transformants will develop roots in about 1-2 weeks and form plantlets. After the plantlets are about 3-5 cm in height, they are placed in sterile soil in fiber pots. Those of skill in the art will realize that different acclimation procedures are used to obtain transformed plants of different species. For example, after developing a root and shoot, cuttings, as well as somatic embryos of transformed plants, are transferred to medium for establishment of plantlets. For a description of selection and regeneration of transformed plants, see, e.g., Dodds and Roberts (1995) Experiments in Plant Tissue Culture, 3rd Ed., Cambridge University Press.

[0138] The transgenic plants of this invention can be characterized either genotypically or phenotypically to evaluate the presence of an exogenous nucleic acid, e.g., a polynucleotide of the invention. Genotypic analysis can be performed by any of a number of well-known techniques, including PCR amplification of genomic DNA and hybridization of genomic DNA with specific labeled probes. Phenotypic analysis includes, e.g., survival of plants or plant tissues exposed to a selected biocide or herbicide.

[0139] Essentially any plant can be transformed with the polynucleotides of the invention. Suitable plants include agronomically and horticulturally important species. Such species include, but are not restricted to members of the families: Graminae (including corn, rye, triticale, barley, millet, rice, wheat, oats, etc.); Leguminosae (including pea, beans, lentil, peanut, yam bean, cowpeas, velvet beans, soybean, clover, alfalfa, lupine, vetch, lotus, sweet clover, wisteria, and sweetpea); Compositae (the largest family of vascular plants, including at least 1,000 genera, including important commercial crops such as sunflower) and Rosaciae (including raspberry, apricot, almond, peach, rose, etc.), as well as nut plants (including, walnut, pecan, hazelnut, etc.), and forest trees (including Pinus, Quercus, Pseutotsuga, Sequoia, Populus, etc.). The ability to modulate growth of commercially relevant plants using the nucleic acids and proteins of the invention provides a clear utility for such nucleic acids and proteins.

[0140] Additional targets for modification by the polynucleotides of the invention, as well as those specified above, include plants from the genera: Agrostis, Allium, Antirrhinum, Apium, Arachis, Asparagus, Atropa, Avena (e.g., oats), Bambusa, Brassica, Bromus, Browaalia, Camellia, Cannabis, Capsicum, Cicer, Chenopodium, Chichorium, Citrus, Coffea, Coix, Cucumis, Curcubita, Cynodon, Dactylis, Datura, Daucus, Digitalis, Dioscorea, Elaeis, Eleusine, Festuca, Fragaria, Geranium, Gossypium, Glycine, Helianthus, Heterocallis, Hevea, Hordeum (e.g., barley), Hyoscyamus, Ipomoea, Lactuca, Lens, Lilium, Linum, Lolium, Lotus, Lycopersicon, Majorana, Malus, Mangifera, Manihot, Medicago, Nemesia, Nicotiana, Onobrychis, Oryza (e.g., rice), Panicum, Pelargonium, Pennisetum (e.g., millet), Petunia, Pisum, Phaseolus, Phleum, Poa, Prunus, Ranunculus, Raphanus, Ribes, Ricinus, Rubus, Saccharum, Salpiglossis, Secale (e.g., rye), Senecio, Setaria, Sinapis, Solanum, sorghum, Stenotaphrum, Theobroma, Trifolium, Trigonella, Triticum (e.g., wheat), Vicia, Vigna, Vitis, Zea (e.g., corn), the Olyreae, the Pharoideae, and many others. As noted, plants in the family Brassicaceae are a particularly favored target plants for the methods of the invention.

[0141] Common crop plants which are targets of the present invention include corn, rice, triticale, rye, cotton, soybean, sorghum, wheat, oats, barley, millet, sunflower, canola, peas, beans, lentils, peanuts, yam beans, cowpeas, velvet beans, clover, alfalfa, lupine, vetch, lotus, sweet clover, wisteria, sweetpea, and nut plants (e.g., walnut, pecan, etc).

[0142] In cases where expression in the plant chloroplast is desired, the polynucleotide of the invention is modified by the addition of a chloroplast transit sequence peptide to facilitate translocation of the gene products into the chloroplasts. Additionally, methods are available in the art to accomplish transformation directly into the chloroplast accompanied by expression of the transformed polynucleotides (e.g., Daniell et al. (1998) Nature Biotechnology 16:346; O'Neill et al. (1993) The Plant Journal 3:729; Maliga (1993) TIBTECH 11:1). In such cases, it is desirable to employ expression vectors that are designed to specifically to function in the chloroplast. Typically, the coding sequence, e.g., a polynucleotide sequence of the invention, is flanked by two regions of homology to the chloroplastid genome to effect a homologous recombination with the chloroplast genome; often a selectable marker gene is also present within the flanking plastid DNA sequences to facilitate selection of genetically stable transformed chloroplasts in the resultant transplastonic plant cells (see, e.g., Maliga (1993) and Daniell (1998), and references cited therein).

[0143] Polypeptide Production and Recovery

[0144] Following transduction of a suitable host cell line or strain, and growth of the host cells to an appropriate cell density, the selected promoter is induced by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. The secreted polypeptide product is then recovered from the culture medium. Alternatively, cells can be harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification. Eukaryotic or microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents, or other methods, which are well know to those skilled in the art.

[0145] Expressed polypeptides can be recovered and purified from recombinant cell cultures by any of a number of methods well known in the art, including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography (e.g., using any of the tagging systems noted herein), hydroxylapatite chromatography, and lectin chromatography. Protein refolding steps can be used, as desired, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed in the final purification steps. In addition to the references noted above, a variety of purification methods are well known in the art, including, e.g., those set forth in Sandana (1997) Bioseparation of Proteins, Academic Press, Inc.; and Bollag et al. (1996) Protein Methods, 2nd Edition Wiley-Liss, NY; Walker (1996) The Protein Protocols Handbook Humana Press, NJ, Harris and Angal (1990) Protein Purification Applications: A Practical Approach IRL Press at Oxford, Oxford, England; Harris and Angal Protein Purification Methods: A Practical Approach IRL Press at Oxford, Oxford, England; Scopes (1993) Protein Purification: Principles and Practice 3rd Edition Springer Verlag, NY; Janson and Ryden (1998) Protein Purification: Principles, High Resolution Methods and Applications. Second Edition Wiley-VCH, NY; and Walker (1998) Protein Protocols on CD-ROM Humana Press, NJ.

[0146] Alternatively, cell-free transcription/translation systems can be employed to produce polypeptides, e.g., corresponding to SEQ ID NO: 31 through SEQ ID NO: 60, subsequences thereof or sequences or subsequences encoded by the polynucleotides of the invention. A number of suitable in vitro transcription and translation systems are commercially available. A general guide to in vitro transcription and translation protocols is found in Tymms (1995) In vitro Transcription and Translation Protocols: Methods in Molecular Biology Volume 37, Garland Publishing, NY.

[0147] In addition, the polypeptides, or subsequences thereof, e.g., subsequences comprising antigenic peptides, can be produced manually or by using an automated system, by direct peptide synthesis using solid-phase techniques (see, Stewart et al. (1969) Solid-Phase Peptide Synthesis, W H Freeman Co, San Francisco; Merrifieid J (i963) J. Am. Chem. Soc. 85:2149-2154). Exemplary automated systems include the Applied Biosystems 431A Peptide Synthesizer (Perkin Elmer, Foster City, Calif.). If desired, subsequences can be chemically synthesized separately, and combined using chemical methods to provide full-length polypeptides.

[0148] Conservatively Modified Variations

[0149] The polypeptides of the invention include, e.g., those presented in SEQ ID NO: 31 to SEQ ID NO: 60, but also similar polypeptides such as, e.g., homologues, peptides synthesized with modified amino acids, subsequences, peptides with conservative modifications, etc.

[0150] For example, the polypeptides of the present invention include conservatively modified variations of SEQ ID NO: 31 to SEQ ID NO: 60. Such conservatively modified variations comprise substitutions, additions, or deletions which alter, add or delete a single amino acid or a small percentage of amino acids (typically less than about 5%, more typically less than about 4%, 2%, or 1%) in any of SEQ ID NO: 31 to SEQ ID NO: 60. Typically, substitutions of amino acids are conservative substitutions according to the six substitution groups set forth in Table 1 (supra).

[0151] For example, a conservatively substituted variation of the polypeptide identified herein as SEQ ID NO: 31 will contain “conservative substitutions”, according to the six groups defined above, in up to 17 residues (i.e., 5% of the amino acids) in the 346 amino acid polypeptide.

[0152] For example, if four conservative substitutions were localized in the region corresponding to amino acids 2-26 of SEQ ID NO: 31, examples of conservatively substituted variations of this region,

[0153] ALKSKLVSL LFLIATLSST FAASFS include:

[0154] AMKSKLLSL LFLIAALSST FAASWS and

[0155] ALRSKLVSL LFIIATLTST FAASYS and the like, in accordance with the conservative substitutions listed in Table 1 (in the above example, conservative substitutions are underlined). Listing of a protein sequence herein, in conjunction with the above substitution table, provides an express listing of all conservatively substituted proteins.

[0156] Finally, the addition of sequences which do not alter the encoded activity of a nucleic acid molecule, such as the addition of a non-functional sequence, provides conservative variations of the basic nucleic acid.

[0157] The polypeptides of the invention, including conservatively substituted sequences, can be present as part of larger polypeptide sequences such as occur upon the addition of one or more domains for purification of the protein (e.g., poly his segments, FLAG tag segments, etc.), e.g., where the additional functional domains have little or no effect on the activity of the protein, or where the additional domains can be removed by post synthesis processing steps such as by treatment with a protease.

[0158] Modified Amino Acids

[0159] Expressed polypeptides of the invention can contain one or more modified amino acid. The presence of modified amino acids can be advantageous in, for example, (a) increasing polypeptide serum half-life, (b) reducing polypeptide antigenicity, (c) increasing polypeptide storage stability. Amino acid(s) are modified, for example, co-translationally or post-translationally during recombinant production (e.g., N-linked glycosylation at N-X-S/T motifs during expression in mammalian cells), or modified by synthetic means (e.g., via PEGylation).

[0160] Non-limiting examples of a modified amino acid include a glycosylated amino acid, a sulfated amino acid, a prenlyated (e.g., farnesylated, geranylgeranylated) amino acid, an acetylated amino acid, an acylated amino acid, a PEG-ylated amino acid, a biotinylated amino acid, a carboxylated amino acid, a phosphorylated amino acid, and the like, as well as amino acids modified by conjugation to, e.g., lipid moieties or other organic derivatizing agents. References adequate to guide one of skill in the modification of amino acids are replete throughout the literature. Example protocols are found in Walker (1998) Protein Protocols on CD-ROM Human Press, Towata, N.J.

[0161] Antibodies

[0162] The polypeptides of the invention can be used to produce antibodies specific for the polypeptides of SEQ ID NO: 31-SEQ ID NO: 60, and conservative variants thereof. Antibodies specific for, e.g., SEQ ID NOs: 31-60, and related variant polypeptides are useful, e.g., for screening and identification purposes, e.g., related to the activity, distribution, and expression of target polypeptides.

[0163] Antibodies specific for the polypeptides of the invention can be generated by methods well known in the art. Such antibodies can include, but are not limited to, polyclonal, monoclonal, chimeric, humanized, single chain, Fab fragments and fragments produced by an Fab expression library.

[0164] Polypeptides do not require biological activity for antibody production. The full length polypeptide, subsequences, fragments or oligopeptide can be antigenic. Peptides used to induce specific antibodies typically have an amino acid sequence of at least about 10 amino acids, and often at least 15 or 20 amino acids. Short stretches of a polypeptide, e.g., selected from among SEQ ID NO: 31-SEQ ID NO: 60, can be fused with another protein, such as keyhole limpet hemocyanin, and antibody produced against the chimeric molecule.

[0165] Numerous methods for producing polyclonal and monoclonal antibodies are known to those of skill in the art, and can be adapted to produce antibodies specific for the polypeptides of the invention, e.g., corresponding to SEQ ID NO: 31-SEQ ID NO: 60. See, e.g., Coligan (1991) Current Protocols in Immunology Wiley/Greene, NY; and Harlow and Lane (1989) Antibodies: A Laboratory Manual Cold Spring Harbor Press, NY; Stites et al. (eds.) Basic and Clinical Immunology (4th ed.) Lange Medical Publications, Los Altos, Calif., and references cited therein; Goding (1986) Monoclonal Antibodies: Principles and Practice (2d ed.) Academic Press, New York, N.Y.; Fundamental Immunology, e.g., 4th Edition (or later), W. E. Paul (ed.), Raven Press, N.Y. (1998); and Kohler and Milstein (1975) Nature 256: 495-497. Other suitable techniques for antibody preparation include selection of libraries of recombinant antibodies in phage or similar vectors. See, Huse et al. (1989) Science 246: 1275-1281; and Ward, et al. (1989) Nature 341: 544-546. Specific monoclonal and polyclonal antibodies and antisera will usually bind with a KD of at least about 0.1 μM, preferably at least about 0.01 μM or better, and most typically and preferably, 0.001 μM or better.

[0166] Defining Polypeptides by Immunoreactivity

[0167] The polypeptides of the invention listed in the sequence listing herein, as well as novel variants derived therefrom, which are also encompassed within the present invention, provide a variety of structural features which can be recognized, e.g., in immunological assays. The generation of antisera which specifically binds the polypeptides of the invention, as well as the polypeptides which are bound by such antisera, are a feature of the invention.

[0168] The invention includes polypeptides that specifically bind to or that are specifically immunoreactive with an antibody or antisera generated against an immunogen comprising an amino acid sequence, e.g., selected from one or more of SEQ ID NO: 31 to SEQ ID NO: 60. To eliminate cross-reactivity with non related polypeptides, the antibody or antisera can be subtracted with unrelated polypeptides or proteins.

[0169] In one typical format, the immunological assay uses a polyclonal antiserum which was raised against one or more polypeptide comprising one or more of the sequences corresponding to one or more polypeptides of the invention, such as SEQ ID NO: 31 to SEQ ID NO: 60, or a subsequence thereof (e.g., a substantial subsequence including at least about 30% of the full length sequence provided). Such an antigenic peptide or polypeptide is referred to as an “immunogenic polypeptide.” The resulting antisera is optionally selected to have low cross-reactivity against unrelated polypeptides, e.g., BSA, and any such cross-reactivity can be removed by immunoabsorbtion with one or more of the unrelated polypeptides, or protein preparations, prior to use of the polyclonal antiserum in the immunoassay.

[0170] In order to produce antisera for use in an immunoassay, one or more of the immunogenic polypeptides is produced and purified as described herein. For example, a recombinant protein can be produced in a bacterial host. An inbred strain of mice (used in this assay because results are more reproducible due to the virtual genetic identity of the mice)can be immunized with the immunogenic protein(s) in combination with a standard adjuvant, such as Freund's adjuvant, and a standard mouse immunization protocol (see, Harlow and Lane (1988) Antibodies, A Laboratory Manual, Cold Spring Harbor Publications, New York, for a standard description of antibody generation, immunoassay formats and conditions that can be used to determine specific immunoreactivity). Alternatively, one or more synthetic or recombinant polypeptide derived from the sequences disclosed herein can be conjugated to a carrier protein and used as an immunogen.

[0171] Polyclonal sera are collected and titered against the immunogenic polypeptide in an immunoassay, for example, a solid phase immunoassay with one or more of the immunogenic proteins immobilized on a solid support. Polyclonal antisera with a titer of 106 or greater are selected, pooled and subtracted with the control unrelated polypeptides to produce subtracted pooled titered polyclonal antisera.

[0172] If desired, the subtracted pooled titered polyclonal antisera are tested for cross reactivity against any unrelated polypeptides. Discriminatory binding conditions are determined for the subtracted titered polyclonal antisera which result in at least about a 5-fold to 10-fold higher signal to noise ratio for binding of the titered polyclonal antisera to the immunogenic polypeptide of interest as compared to binding to the unrelated polypeptide. That is, the stringency of the binding reaction can be adjusted by the addition of non-specific competitors such as albumin or non-fat dry milk, or by adjusting salt conditions, temperature, and/or the like. These binding conditions can be used in subsequent assays for determining whether a test polypeptide is specifically bound by the pooled subtracted polyclonal antisera. In particular, test polypeptides which show at least a 2-5× (i.e., 2-fold to 5-fold) and preferably 10× or higher signal to noise ratio than for the control polypeptides under discriminatory binding conditions, and at least about a half the signal to noise ratio as compared to the immunogenic polypeptide(s) (and typically 90% or more of the signal to noise ratio shown for the immunogenic peptide), shares substantial structural similarity with the immunogenic polypeptide as compared to unrelated polypeptides, and is, therefore, a polypeptide of the invention.

[0173] Such methods are also useful for detecting an unknown test protein or polypeptide, which is also specifically bound by the antisera under conditions as described above. In one format, the immunogenic polypeptide(s) are immobilized to a solid support which is exposed to the subtracted pooled antisera. Test proteins are added to the assay to compete for binding to the pooled subtracted antisera. The ability of the test protein(s) to compete for binding to the pooled subtracted antisera as compared to the immobilized protein(s) is compared to the ability of the immunogenic polypeptide(s) added to the assay to compete for binding (the immunogenic polypeptides compete effectively with the immobilized immunogenic polypeptides for binding to the pooled antisera). The percent cross-reactivity for the test proteins is calculated, using standard calculations.

[0174] In a parallel assay, the ability of the control proteins to compete for binding to the pooled subtracted antisera is determined as compared to the ability of the immunogenic polypeptide(s) to compete for binding to the antisera. Again, the percent cross-reactivity for the control polypeptides is calculated, using standard calculations. Where the percent cross-reactivity is at least 5-10× as high for the test polypeptides, the test polypeptides are said to specifically bind the pooled subtracted antisera.

[0175] In general, the immunoabsorbed and pooled antisera can be used in a competitive binding immunoassay as described herein to compare any test polypeptide to the immunogenic polypeptide(s). In order to make this comparison, the two polypeptides are each assayed at a wide range of concentrations and the amount of each polypeptide required to inhibit 50% of the binding of the subtracted antisera to the immobilized protein is determined using standard techniques. If the amount of the test polypeptide required required to inhibit 50% of the binding of the subtracted antisera to the immobilized protein is less than twice the amount of the immunogenic polypeptide that is required, then the test polypeptide is said to specifically bind to an antibody generated to the immunogenic protein; provided the amount is at least about 5-10× as high as for a control polypeptide.

[0176] As an additional determination of specificity, the pooled antisera can be optionally fully immunosorbed with the immunogenic polypeptide(s) (rather than the control polypeptides) until little or no binding of the resulting immunogenic polypeptide subtracted pooled antisera to the immunogenic polypeptide(s) used in the immunosorbtion is detectable. This fully immunosorbed antisera is then tested for reactivity with the test polypeptide. If little or no reactivity is observed (i.e., no more than 2× the signal to noise ratio observed for binding of the fully immunosorbed antisera to the immunogenic polypeptide), then the test polypeptide can be deemed specifically bound by the antisera elicited by the immunogenic protein.

[0177] Predicting Plant Growth Traits

[0178] The presence of sequences of the invention, or the amount of their expression products, can be predictive of plant growth traits before they actually become apparent. Detection of polynucleotide sequences of the invention in plant cells can predict plant growth traits, such as root length or leaf mass, well before the maturity of a plant. The presence of particular combinations of polynucleotide sequences of the invention can predict one plant growth trait, e.g., large root mass, while a different combination of polynucleotides of the invention can predict another plant growth trait, e.g., short stalk length. In addition, the amount of expression products, such as the quantity of mRNAs transcribed from polynucleotides of the invention, or amount of translated polypeptides of the invention, can be predictive of plant growth traits. The presence of sequences of the invention, combinations of the sequences, and amount of expression products can predict plant growth traits, e.g., in cultured plant cells and immature plants. Such a predictive information can be useful in, e.g., rapid screening of desirable plants in culture or cultivation.

[0179] The probes and marker sets of the invention are favorably employed in methods for predicting plant growth traits in an individual specimen, such as cultured plant cells. Nucleic acids of a marker set or individual probes including one or more polynucleotides of the invention, as described, e.g., in the section entitled “Probes,” are hybridized, e.g., as an array, to a DNA or RNA sample from a subject cell or tissue sample. Upon hybridization of the sample to at least a subset of the probes, a signal is detected corresponding to at least one nucleic acid or to expression or activity of an expression product correlatable to a plant growth trait. When expression is detected, the evaluation can be made on a qualitative basis, that is, detecting whether or not an expression product (or multiple expression products) are expressed in a subject cell or tissue sample. Alternatively, the evaluation can be quantitative, to determine whether levels are adequate to provide the desired trait.

[0180] While a variety of biological samples reflective of a growth trait can be employed, the specimen is usually selected for ease of acquisition, to minimize invasiveness of the collection procedure to the subject, or to focus on the tissue of interest. Thus, in the context of individual whole plants, individual leaves, roots or branches can be preferred samples, and can be obtained simple cutting. In the case of recombinant inbred lines (RILs) entire individual plants can be sampled knowing they are representative of other available individuals of the line.

[0181] For example, a marker set including a plurality (e.g., several or all of SEQ ID NO: 1 through SEQ ID NO: 30 or of SEQ ID NO: 61 through SEQ ID NO: 403) of the polynucleotides of the invention, can be hybridized individually, or as an array, to an RNA or cDNA sample produced, e.g., by a reverse transcription-polymerase chain reaction (RT-PCR), from a subject RNA sample. Typically, prior to hybridization of the probes or array to a subject or “test” specimen, the probe or array is validated and/or calibrated by comparing samples obtained from classes of subjects known to differ with respect to their growth traits. For example, specimens from individuals displaying a high root mass trait are compared to subjects that display low root mass relative to the general population of individual plants. In one embodiment, for example, nucleic acid SEQ ID NO: 397 through SEQ ID NO: 403 have been associated with enhanced root growth in Arabidopsis plants exposed to environments containing either ammonium sulfate or ammonium nitrate fertilizer. See copending provisional application 60/344,499, Identification of Genes Controlling Complex Traits, by Benjamin A. Bowen, et al., filed Dec. 28, 2001.

[0182] Alternatively, a marker set including a plurality of antibodies, or other binding proteins, specific for a polypeptide of the invention, e.g., SEQ ID NO: 31-SEQ ID NO: 60, are employed as individual probes or marker sets to evaluate expression of proteins, e.g., corresponding to SEQ ID NO: 31-SEQ ID NO: 60 in a cell or tissue specimen. In this case, rather than, or in addition to, preparing RNA from a sample, proteins are recovered and exposed to the probe or marker set of antibodies, in liquid phase or with either the target of antibody immobilized on a solid substrate, such as a solid phase array.

[0183] Patterns of expression that correlate to a particular growth trait are detected by hybridization to one or more probes. In some embodiments, a single probe with a high predictive value is favored, e.g., for ease of handling and cost containment. In other embodiments multiple probes, e.g., the entire marker set, are preferred, e.g., to increase sensitivity or diagnostic or prognostic value. Optimal probes and marker sets are readily ascertained on an empirical basis.

[0184] Alternatively, the invention provides an oligonucleotide or polynucleotide probe that detects sequence polymorphisms rather than expression differences between specimens from individuals with different growth traits. Polymorphisms at a nucleotide level can correspond either directly or indirectly to the gene of interest underlying the growth trait, and can be detected in any of several ways, for example, as restriction fragment length polymorphisms, by allele specific hybridization, as amplification length polymorphisms, and the like.

[0185] For example, oligonucleotide probes including conservative variants of a polynucleotide sequences can be selected which correspond to polymorphic variations in a target sequence. For example, a probe pair incorporating a single variant nucleotide can be designed to hybridize under allele specific hybridization conditions to allelic target sequences in which one allele is correlated to a fast growth trait and the other allele indicates a relatively slow growth trait. For example, probe sequences are selected from among SEQ ID NO: 1-SEQ ID NO: 30 (or other polynucleotides of the invention) and variants thereof. In some instances, for example, where the cDNA or chromosomal segment has been sequenced and a particular nucleotide polymorphism is associated with a high growth trait, the probes can be chosen to detect the nucleotide polymorphism, e.g., by allele specific hybridization.

[0186] Modulating Plant Growth Traits

[0187] The invention also provides experimental methods for modulating plant growth traits in vitro and in vivo. Tissue culture and plant models useful for elucidating the molecular mechanisms underlying growth traits as well as for screening and evaluating potential growth control targets are produced by modulating expression or activity of polypeptides (e.g., represented by SEQ ID NO: 31-SEQ ID NO: 60, and conservative variants thereof) encoded by the nucleic acids of the invention.

[0188] For example, plant cells in culture can be transfected with a nucleic acid, e.g., comprising a polynucleotide sequence selected from SEQ ID NO: 1 through SEQ ID NO: 30, to produce cells that express a polypeptide involved in plant growth. It will be understood, that where exogenous polynucleotide sequences are introduced into cells, tissues or individual plants, that the polynucleotide sequences can be selected from among SEQ ID NO: 1-30, conservative variants thereof, polynucleotide sequences encoding SEQ ID NO: 31-60, or other homologous polynucleotide sequences such as polynucleotides sequences that hybridize thereto, or polynucleotides that are at least 70%, (or at least about 75%, about 80%, about 85%, about 90%, or at least about 95%) identical thereto. In some cases, it is preferable to link the polynucleotide sequence of interest to the regulatory sequences with which it is typically associated in vivo in nature. Alternatively, in cases where constitutive expression at levels that are in excess of those found in nature is desired, exogenous promoters and enhancers can be employed, as described in detail in the section entitled “Vectors, Promoters and Expression Systems.”

[0189] Expression and/or activity of the gene or polypeptide can also be modulated in a negative manner, that is, suppressed. For example, knock out mutations can be produced by homologous recombination of an exogenous gene homologue, e.g., bearing a stop codon, and/or insertion of, e.g., a selectable marker, that disrupts production of an intact transcript. Alternatively, vectors incorporating the sequence of interest in the antisense orientation can be introduced to suppress translation at a post-transcriptional level.

[0190] Alternatively, cell lines, e.g., plant or bacterial cells, that express a polypeptide of the invention, e.g., corresponding to one or more of SEQ ID NO: 31-SEQ ID NO: 60, or a subsequence thereof, into which vectors have been transduced that randomly activate expression of associated endogenous sequences upon integration can be isolated. Such vectors have been described, e.g., by Harrington et al. “Creation of genome-wide protein expression libraries using random activation of gene expression.” Nature Biotechnology 19: 440-445, which is incorporated herein by reference. Typically, the vector is constructed with a strong exogenous promoter linked to an exon and an unpaired splice donor site. Upon integration into the genome, splicing with a proximal splice-acceptor site occurs, activating expression of a chimeric transcript encoding at least a portion of the endogenous gene. Cells expressing a polypeptide of interest e.g., SEQ ID NO: 31-SEQ ID NO: 60 can be selected by well known methods, including those based on phenotypic screening methods, antibody or receptor binding, RNA analytical methods, e.g., RT-PCR, northern analysis, MPSS, and the like. By preference, the screening is performed in a high-throughput format.

[0191] The above-described methods for producing cell culture or plant cultivation model systems can be adapted for use in the screening of growth modulating environmental factors, e.g., aimed at optimizing application of water, fertilizer or herbicides. For example, it is desirable to select promoters and enhancers that are modulated in response to nutrients or plant hormones.

[0192] Following introduction of environmental factors, e.g., application of fertilizers, herbicides, or other molecules that affect plant growth traits, altered expression or activity can be detected at the RNA or protein level. Detection of altered levels of RNA is most conveniently accomplished by such methods as RT-PCR, MPSS, or northern analysis. Protein expression is conveniently monitored using, e.g., antibody based detection methods, such as ELISA'S, immunoprecipitations, or immunohistochemical methods including western analysis. In each of these procedures, the sample including the expressed protein of interest is reacted with an antibody (e.g., monoclonal antibody) or antiserum specific for the protein of interest. Methods for generating specific antibodies are well known and further details are provided above in the section entitled “Antibodies.”

[0193] The cell culture models can be used to identify chemical agents capable of favorably regulating the expression or activity of a polypeptide of interest, e.g., a polypeptide selected from among SEQ ID NO: 31-60, in a cell culture system as described above. Most typically, this involves exposing the cells to a chemical or biological composition, e.g., a small organic molecule, or biological macromolecule such as a protein, e.g., an antibody, binding protein, or macromolecular cofactor. Following exposure to the one or more compositions, for example, members of a chemical or biological composition library, such as a combinatorial chemical library, a library of peptide or polypeptide products expressed from a library of nucleic acids, an antibody (or other polypeptide) display library such as a phage display library, etc., modulation of the polypeptide of interest is detected. As discussed above, modulation of the polypeptide can be detected as an alteration in expression at the level of transcription or translation, or as an alteration in the activity of the encoded protein or polypeptide. In some instances, it is desirable to monitor expression or activity of multiple expression products in the same cell, or cell line. The monitored expression products, can be exogenous, i.e., introduced as described above, or endogenous, such as transcripts or polypeptides whose expression or activity is dependent on the amount or activity of a polypeptide of interest.

[0194] In cases where the expression or activity of multiple products are of interest, or where the effect of a plurality of different compounds on the expression or activity of one or more expression products, e.g., screening for growth modulating agents as described above, the monitoring assay is conveniently performed in an array. For example, cells can be arrayed by aliquoting into the wells of a multiwell plate, e.g., a 96, 384, 1536, or other convenient format selected according to available equipment. The arrayed cells can exposed to members of a composition library, and the cells sampled and monitored by, e.g., FACS, immunohistochemisty, ELISA, etc. Alternatively, nucleic acids or proteins can be prepared from the arrayed cells, in a manual, semi-automatic or automated procedure, and the products arranged in a liquid or solid phase array for evaluation. Additional details regarding arrays are provided above in the section entitled “Marker Sets.” Alternative high throughput processing methods, such as microfluidic devices, are also available, and can favorably be employed in the context of monitoring modulation of expression products, e.g., corresponding to SEQ ID NO: 1-403.

[0195] Typically, when processing and evaluating large numbers of samples, e.g., in a high throughput assay, data relating to expression or activity is recorded in a database, typically the database includes character strings representing the data recorded on a computer or in a computer readable medium.

[0196] In addition to tissue culture systems, transgenic plants can be produced which have integrated one or more of the polynucleotide sequences of the invention, e.g., selected from SEQ ID NO: 1 to SEQ ID NO: 30. In this context, commonly used experimental plants include, e.g., Arabidopsis and tobacco.

[0197] Such transgenic plant models are useful, in addition to the cultured cells discussed above, for the evaluation of chemical agents suitable for the modulation plant growth traits. Transgenic plant models, e.g., expressing a polypeptide selected from SEQ ID NO: 31-60, are suitable for evaluating fertilizers, hormones and herbicides useful in modulation of plant growth. For example, following administration of a particular herbicide to a transgenic plant expressing a polypeptide of the invention, leaf growth can be monitored. Monitoring can also involve detecting altered expression or activity of an expression product corresponding to one or more of SEQ ID NO: 1-403 as discussed above.

[0198] Kits and Reagents

[0199] Certain embodiments of the present invention can be optionally provided to a user as a kit. For example, a kit of the invention can contain one or more nucleic acid, polypeptide, antibody, and/or cell line described herein. Most often, the kit contains a diagnostic nucleic acid or polypeptide, e.g., antibody, probe set, e.g., as a cDNA microarray packaged in a suitable container, or other nucleic acid such as one or more expression vector. The kit typically further comprises, one or more additional reagents, e.g., substrates, labels, primers, for labeling expression products, tubes and/or other accessories, reagents for collecting samples, buffers, hybridization chambers, cover slips, etc. The kit optionally further comprises an instruction set or user manual detailing preferred methods of using the kit components for discovery or application of gene sets. When used according to the instructions, the kit can be used, e.g., for evaluating expression or polymorphisms in a plant sample, e.g., for evaluating growth traits.

[0200] Digital Systems

[0201] The present invention provides digital systems, e.g., computers, computer readable media, and integrated systems, comprising character strings corresponding to the sequence information herein for the polypeptides and nucleic acids herein, including, e.g., those sequences listed herein and the various silent substitutions and conservative variations thereof. Integrated systems can further include, e.g., gene synthesis equipment for making genes corresponding to the character strings.

[0202] Various methods known in the art can be used to detect homology or similarity between different character strings, or can be used to perform other desirable functions such as to control output files, provide the basis for making presentations of information including the sequences, and the like. Examples include BLAST, discussed supra. Computer systems of the invention can include such programs, e.g., in conjunction with one or more data file or data base comprising a sequence as noted herein.

[0203] Thus, different types of homology and similarity of various stringency and length can be detected and recognized in the integrated systems herein. For example, many homology determination methods have been designed for comparative analysis of sequences of biopolymers, for spell-checking in word processing, and for data retrieval from various databases. With an understanding of double-helix pair-wise complement interactions among 4 principal nucleobases in natural polynucleotides, models that simulate annealing of complementary homologous polynucleotide strings can also be used as a foundation of sequence alignment or other operations typically performed on the character strings corresponding to the sequences herein (e.g., word-processing manipulations, construction of figures comprising sequence or subsequence character strings, output tables, etc.).

[0204] Thus, standard desktop applications such as word processing software (e.g., Microsoft Word™ or Corel WordPerfect™) and database software (e.g., spreadsheet software such as Microsoft Excel™, Corel Quattro Pro™, or database programs such as Microsoft Access™ or Paradox™) can be adapted to the present invention by inputting a character string corresponding to one or more polynucleotides and polypeptides of the invention (either nucleic acids or proteins, or both). For example, a system of the invention can include the foregoing software having the appropriate character string information, e.g., used in conjunction with a user interface (e.g., a GUI in a standard operating system such as a Windows, Macintosh or LINUX system) to manipulate strings of characters corresponding to the sequences herein. As noted, specialized alignment programs such as BLAST can also be incorporated into the systems of the invention for alignment of nucleic acids or proteins (or corresponding character strings).

[0205] Systems in the present invention typically include a digital computer with data sets entered into the software system comprising any of the sequences herein. The computer can be, e.g., a PC (Intel x86 or Pentium chip-compatible DOS™, OS2™ WINDOWS™ WINDOWS NT™, WINDOWS95™, WINDOWS98™ LINUX based machine, a MACINTOSH™, Power PC, or a UNIX based (e.g., SUN™ work station) machine) or other commercially common computer which is known to one of skill. Software for aligning or otherwise manipulating sequences is available, or can easily be constructed by one of skill using a standard programming language such as Visualbasic, Fortran, Basic, Java, or the like.

[0206] Any controller or computer optionally includes a monitor which is often a cathode ray tube (“CRT”) display, a flat panel display (e.g., active matrix liquid crystal display, liquid crystal display), or others. Computer circuitry is often placed in a box which includes numerous integrated circuit chips, such as a microprocessor, memory, interface circuits, and others. The box also optionally includes a hard disk drive, a floppy disk drive, a high capacity removable drive such as a writeable CD-ROM, and other common peripheral elements. Inputting devices such as a keyboard or mouse optionally provide for input from a user and for user selection of sequences to be compared or otherwise manipulated in the relevant computer system.

[0207] The computer typically includes appropriate software for receiving user instructions, either in the form of user input into a set parameter fields, e.g., in a GUI, or in the form of preprogrammed instructions, e.g., preprogrammed for a variety of different specific operations. The software then converts these instructions to appropriate language for instructing the operation of the fluid direction and transport controller to carry out the desired operation.

[0208] The software can also include output elements for controlling nucleic acid synthesis (e.g., based upon a sequence or an alignment of a sequences herein) or other operations.

[0209] General Molecular Techniques

[0210] In the context of the invention, nucleic acids and/or proteins are manipulated according to well known molecular biology methods. Detailed protocols for numerous such procedures are described in, e.g., in Ausubel et al. Current Protocols in Molecular Biology (supplemented through 2000) John Wiley & Sons, New York (“Ausubel”); Sambrook et al. Molecular Cloning—A Laboratory Manual (2nd Ed.), Vol. 1-3, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989 (“Sambrook”), and Berger and Kimmel Guide to Molecular Cloning Techniques, Methods in Enzymology volume 152 Academic Press, Inc., San Diego, Calif. (“Berger”).

[0211] In addition to the above references, protocols for in vitro amplification techniques, such as the polymerase chain reaction (PCR), the ligase chain reaction (LCR), Qβ-replicase amplification, and other RNA polymerase mediated techniques (e.g., NASBA), useful e.g., for amplifying cDNA probes of the invention, are found in Mullis et al. (1987) U.S. Pat. No. 4,683,202; PCR Protocols A Guide to Methods and Applications (Innis et al. eds) Academic Press Inc. San Diego, Calif. (1990) (“Innis”); Arnheim and Levinson (1990) C&EN 36; The Journal Of NIH Research (1991) 3:81; Kwoh et al. (1989) Proc Natl Acad Sci USA 86, 1173; Guatelli et al. (1990) Proc Natl Acad Sci USA 87:1874; Lomell et al. (1989) J Clin Chem 35:1826; Landegren et al. (1988) Science 241:1077; Van Brunt (1990) Biotechnology 8:291; Wu and Wallace (1989) Gene 4: 560; Barringer et al. (1990) Gene 89:117, and Sooknanan and Malek (1995) Biotechnology 13:563. Additional methods, useful for cloning nucleic acids in the context of the present invention, include Wallace et al. U.S. Pat. No. 5,426,039. Improved methods of amplifying large nucleic acids by PCR are summarized in Cheng et al. (1994) Nature 369:684 and the references therein.

[0212] Certain polynucleotides of the invention, e.g., SEQ ID NO: 61-SEQ ID NO: 403, can be synthesized utilizing various solid-phase strategies involving mononucleotide- and/or trinucleotide-based phosphoramidite coupling chemistry. For example, nucleic acid sequences can be synthesized by the sequential addition of activated monomers and/or trimers to an elongating polynucleotide chain. See e.g., Caruthers, M. H. et al. (1992) Meth Enzymol 211:3. In lieu of synthesizing the desired sequences, essentially any nucleic acid can be custom ordered from any of a variety of commercial sources, such as The Midland Certified Reagent Company (mcrc@oligos.com), The Great American Gene Company (www.genco.com), ExpressGen, Inc. (www.expressgen.com), Operon Technologies, Inc. (www.operon.com), and many others.

[0213] Similarly, commercial sources for nucleic acid and protein microarrays are available, and include, e.g., Affymetrix, Santa Clara, Calif. (http://www.affymetrix.com/); and Agilent, Palo Alto, Calif. (http://www.agilent.com) Zyomyx, Hayward, Calif. (http://www.zyomyx.com); and Ciphergen Biosciences, Fremont, Calif. (http://www.ciphergen.com/).

EXAMPLES

[0214] The following examples are offered to illustrate, but not to limit, the claimed invention.

Example 1

Growth Gene Combinations in Different Environments

[0215] Genes associated with a particular plant growth trait, such as root length, can vary depending on the environment in which the plant is grown. For example, as described in “Identification of Fenes Controlling Compex Traits” by Benjamin A. Bowen, et al., filed Dec. 28, 2001 (Attorney Docket No. 37-000800US) incorporated herein by reference, gene expression by massively parallel signature sequence (MPSS) analysis was determined for Arabidopsis plants having long roots and short roots in ammonium nitrate fertilizer. FIG. 1 shows differential gene expression between the plants having long and short roots. Similar analysis was carried out comparing gene expression in long root and short root Arabidopsis plants but grown in ammonium sulfate fertilizer. In the ammonium nitrate environment, 56 genes were found to have differential expression between long and short root plants and also to be correlated to root growth by quantitative trait locus (QTL) analysis. In the ammonium sulfate environment. 80 genes were found to have differential expression between long and short root plants and also to be correlated to root growth by QTL analysis. Only 7 genes were found to be correlated in the same direction in both environments. The combination of genes associated with root length was considerably different depending on the nutritional environment. Sequences of the present invention are similarly expressed in unique combinations depending on environmental factors.

Example 2

Genes Associated with Different Plant Growth Traits

[0216] The combination of genes associated with one plant growth trait, such as root length, is often different from the combination of genes associated with another growth trait, such as aerial mass. FIG. 2 shows Arabidopsis QTL plots for three plant growth traits (root length, aerial mass, and root mass). Although there is some overlap of the plots for each trait, QTL analysis would identify a unique combination of differentially expressed genes associated with each trait. For example, differential expression analyses were carried out on long root and short root plants grown with ammonium nitrate fertilizer. Forty-six genes were found to have differential expression between long and short root plants and also to be correlated to root growth by quantitative trait locus (QTL) analysis. The combination of sequences of the present invention also varies uniquely with different plant growth traits.

[0217] While the foregoing invention has been described in some detail for purposes of clarity and understanding, it will be clear to one skilled in the art from a reading of this disclosure that various changes in form and detail can be made without departing from the true scope of the invention. For example, the sequences, techniques and apparatus described above can be used in various combinations. All publications, patents, patent applications, and/or other documents cited in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent, patent application, and/or other document were individually indicated to be incorporated by reference for all purposes.

[0218] Sequence ID Table:

SEQ ID NO. SEQ
1          cacaaatcct aacgccaata gtatagattc aattagaatt aaaaccgatc caagtataga
           ttgattcaat tagaatatgg aattcaaaga gaagattatt gatggactta cacttatcgc
           aaaccatctt cttcttccga gagagaaata tgaagaaacc ctaacgccta aatcaattcg
           aatgggttag agttacgacg aaaacttatc ggtgttgaaa tttttatcta tgtttaaata
           tatttttttt ccttttctgg atttggaaag tcggatatgt ctcgtcaaaa ctcatagcct
           cacaggtatt ttatgccacg aatcgtaata atccacgtgg tacatcaacc aataaaaacg
           ttccacgtgg tacaaccagc gagataccaa gaacttcgag accttcttct ccagatagag
           gctttccggt aaacggcaaa tacccttttc cttcactttc ttcgtcttct cgaatctgag
           agaacgagag atcaacaaca ATGGCGCTCA AATCAAAACT CGTCTCTCTT CTCTTCCTCA
           TAGCAACACT ATCATCCACA TTCGCAGCTT CGTTTTCCGA TTCGGATTCC GATTCAGATC
           TTCTCAACGA ACTTGTATCT CTCAGATCAA CAAGCGAATC AGGCGTAATC CATCTCGATG
           ACCATGGAAT CTCAAAATTC CTAACCTCCG CTTCCACGCC TCGTCCTTAC TCGTTACTCG
           TCTTCTTCGA CGCTACTCAA CTCCACAGCA AAAACGAGCT TCGTCTTCAA GAGCTCCGTC
           GCGAATTCGG CATCGTCTCC GCTTCATTCC TCGCTAACAA CAATGGATCT GAAGGAACTA
           AGCTTTTCTT CTGTGAGATC GAGTTTTCGA AGTCTCAATC TTCGTTCCAG CTCTTTGGCG
           TTAACGCTTT ACCTCACATT CGTCTTGTAA GTCCTTCGAT ATCGAATCTA CGTGATGAAT
           CTGGTCAAAT GGATCAATCG GATTACTCTA GATTAGCTGA ATCAATGGCT GAGTTTGTTG
           AGCAACGAAC TAAACTCAAG GTCGGTCCTA TTCAACGTCC ACCGCTACTT TCGAAACCAC
           AGATCGGTAT TATCGTTGCG TTGATCGTTA TCGCTACTCC GTTTATCATC AAAAGAGTTT
           TGAAAGGAGA AACTATTCTT CATGATACTA GACTTTGGTT ATCTGGTGCT ATCTTCATTT
           ACTTCTTTAG TGTTGCTGGT ACAATGCACA ACATTATCAG GAAAATGCCG ATGTTTCTTC
           AAGATCGTAA CGATCCGAAT AAGCTTGTGT TTTTCTACCA AGGATCTGGA ATGCAGCTTG
           GAGCTGAAGG ATTTGCTGTT GGATTCTTGT ATACTGTTGT TGGATTGCTT TTGGCGTTTG
           TTACCAATGT GCTTGTTCGA GTGAAGAATA TTACTGCACA AAGGTTGATT ATGCTTTTGG
           CTTTGTTCAT ATCGTTCTGG GCTGTGAAGA AAGTTGTTTA CTTGGATAAC TGGAAGACTG
           GATATGGAAT TCATCCGTAT TGGCCATCGA GTTGGCGTTG Attacatcac acttgaggat
           ctctgtttca caaggtaatg gctttagttt tggaaaaaca gttatgggaa ttgagtaatg
           atgtttctgg atgttttgtg tttcgatttg aaatactttt gaatcggtgt agtactacta
           tttcagatgg tttaaaactc cttactgtta cattagtcca ttgttaagtt atttatctga
           atgagtaact tatataacca agaatatggg atctttagtc gattgaatat aggaaccata
           tttggaaatt caggtactgt ttcttgagat cagtctagga ttgttgttat ttggtacatt
           gacactttta gagtttctat gtgtcttcag ccttgcgccc cttgcttact gcatctattc
           agaaaaaggg actttgtgat tgaggatagt gtttctgttt aagcattatg ggaccttatg
           ttttgtcgtt gactgtgtcc tcttctcgtt ttgctctctg ttttagaatg agtctaagta
           a
2          atttaaatgt gttataatat ttgataaaaa atttgaatct ttttaaaaat atatataatt
           gtgttaaaaa aaactatact ttttattatt ttattttatc ttcctttaaa atgttaaatt
           taaatttatt ttcaaaaaat ttgataattt taggcttttt gataatgttt ttcaactttt
           tatataatat ataagtacat attgttttat tctaaaatcg tttagatctt aacgaatagt
           tataggcgtt agacggcctc aactaattgt tataagtgtt agacggaaag ttaccgtccc
           cttagcgttt attttaacat taaaagaaaa gatacatact attaaactaa tggagtatta
           acaagaaaaa aaagaaagag taaaatacga aaggttcctt aagcaagttt ataaatattt
           atagccaaaa acaaaagcaa aaccaaaaat cacaagtaac cccaaaagaa aaaaagcaaa
           gagagaggaa aagaaaaaaa ATGACGAAGA CGATGATGAT CTTTGCGGCG GCGATGACGG
           TGATGGCTTT GCTTTTGGTT CCGACTATTG AAGCACAAAC TGAGTGCGTG AGCAAGCTAG
           TCCCTTGCTT CAACGACCTG AACACGACAA CAACGCCGGT GAAAGAATGT TGCGACTCGA
           TTAAAGAAGC GGTGGAGAAG GAACTTACAT GTCTCTGTAC AATCTACACC AGTCCAGGTT
           TGCTCGCTCA GTTCAACGTC ACCACTGAGA AAGCTCTCGG TCTTAGCCGT CGTTGCAACG
           TCACCACTGA TCTCTCCGCT TGTACCGgta accaatttca ttttctccga tctccgattt
           tttaattttt ttgtcaacaa catgcattat gaatggattt gtggattctg attaatgtga
           atgtgactaa gaaaattagc atagtttttt gtctactgct aacatttttt agatcttgtt
           gagattatga aacagagatt tgcaatttca tatatcagta ttaatcatgt ttttgttttt
           tgtttagCTA AAGGAGCTCC ATCGCCAAAA GCTTCTTTAC CTCCTCCAGC TCCAGgtatg
           aaccaaactc ttcacctact ccttacaatt atttccttga atactttgtt atcaaaaaaa
           aaaaaaaatg aaatattgat cgacttgatt gtgtattaat tgaattattc gattgatttg
           attagtagag ttaattaacc aaatcaaatg gtgttaatca aggcaattat tcaattgata
           ctctaaatcg atcttataat tttcccagat ttttctctct ttttttgttt tctatataaa
           aaacataaac agagtgtgaa tgccagcttt tacttgtgta ctttattttg tctcgagtat
           tgacttgaat aattcggaca aaaccactaa aaaatgaaac ttgtcagatt ttttattttt
           ttataaattt tttatttgtt atttgctgat tgacgatttg tcttatatta tatggatggg
           tttctaaata ttcagCAGGG AATACCAAAA AAGACGCCGG AGCTGGGAAC AAGCTCGCCG
           GTTATGGAGT CACCACCGTG ATCTTGTCTT TGATCTCATC CATCTTCTTC TGAattcctt
           tacccggttt tattattatt agctcaataa attctcgaga tttgtttgct tttggcttaa
           cttatttaat atttaaagaa aaacaaaaag tattttttgt tcacatgtta tgtattatca
           ttgattcatt attgagtccc atgttagtat atttaccggt tataatcgga ctctatcatt
           tgcatatctg atttgagtgt ggatctgtgt tgttaattga tgtaatcttt attatataaa
           ttgaaaatga aaacaaaata taaaaaactg tgttggttta aaggtcccaa tcctcatttt
           ggtaggtttg actaccaact agaaacaata tcatccataa tattgcttct ttgtgctatc
           ttattaaatg taaaccaaga acgcagtttt attctctaat tgtgttcata aattaaacaa
           caaaagaaca gaatcgcaaa tttaattagg cgatgcgagt aacaacagca tgtatagcat
           cagcgagttg agg
3          ctgtatatga cttatcacca tgagattgta ataactctta tctaataata ctcactcaag
           taaaagatcc aataatcttc aaacgaaagt agtaccaggt atgaaactcc agcgttgatg
           atgtgagctt ctcaatatct actagtcaaa gacgcatcgg atcgatcatc ggagttgcat
           cggaatttat cgggaaagaa tggattgggc ccaatgtgga aatgataagt cgtatgggcc
           taaatcattt agtcgtaggc ccaatatgag tttaagctct ttgatatttc agagaatgtt
           attcaattta ttagtaattt tcaaatgata taaattcaat ttattaatca cttggttaaa
           acttatacac gtgaaaaaat gagaaatcat tttagtacat tgttgaccat ctttttcgta
           tagactacta tctctgatct cttgcgagtt aagtcagtaa ctaggaaaat tcagaagcgc
           tctcaatctc aaaaatatcc ATGGCGGCGA TTACAGAATT TCTACCAAAA GAGTACGGAT
           ATGTCGTTCT CGTCCTCGTC TTCTACTGTT TCCTCAACCT CTGGATGGGT GCTCAAGTCG
           GCAGAGCTCG CAAAAGgttt ccacgaaact cctagatcgt taacgcttga attgccgtga
           tttcgccact aaaatcgaat cgaggacgat gctagatcgt tccctttgtt cttgattgga
           atcgaatttt aactgaaatc tgtagattga tgtgacctaa aactagaatt ttgcaatttt
           cgtcctaagt ttttggattc tgtagtctga ttcattgttt tgatgttatc atcagttcga
           tttcaagttt attgaactta cgatttcaat ctgttgtttg tttgttcatc ttctactaat
           tgattagtat gagcgagatt gtcttatcgg ttagatctgt tgtttgttca tcttcaattt
           tgaatgatct cacatgagtc tatgatcttg atgcagGTAC AACGTCCCGT ATCCAACTCT
           ATATGCAATA GAATCAGAAA ACAAAGATGC TAAGCTCTTC AACTGTGTTC AGgtttgaaa
           tatagttaaa acaatacttg tgtgattctg ttttcttgta ctacttgtta ttgagatgtg
           ataaaatttg tggttgtagA GAGGACATCA AAACTCTTTA GAGATGATGC CAATGTATTT
           CATACTGATG ATCCTCGGTG GGATGAAGCA CCCTTGTATC TGTACTGGCC TTGGTTTGCT
           TTACAACGTT AGCCGATTCT TCTACTTTAA AGGTTATGCT ACTGGAGATC CCATGAAGCG
           TCTTACGATC GGgtttgttc ttttatcctc ttatcagtgt tcattatctt tattgattga
           tttagttatg ttagtcaata ggatatagag tttagacttg tatataaggt tgtaacttgc
           aagtatagtt tcattaactg atttcttcgg ttattgtatc aaagcattga tctaaggctc
           taagctcaac cattttccgt tttgcgtatc aaatgtttct cgctttcttt gtctttgatt
           cttgggaaat ttctttgttt ctgcatacag cttttcccat tcttcgtttc tttactcggt
           tctgtattta ctacgacttt gttccacgtc ttcgtctcta aatcgagttt acgtagataa
           tcgttgtaat ctacaatgtt gcagttaagt tagtcagagt aatagttaag agttaagact
           tgtacatacg gttgtaagtg aacattttcc taaactgact tcttctgtta tggtgtcaga
           gcgtgaagct aagctcaacg atttcttcgt gtttctgata agtaacaagc caccaaagtc
           tgattactta tctttctaat ctataatgtt gcagGAAATA CGGTTTCTTG GGGTTGCTAG
           GTCTGATGAT ATGTACCATC TCGTTTGGTG TCACTCTGAT CCTTGCTTGA gctactcgtt
           tctggggtta atgattctct ggtttgctcg aagaatatag aaccaatgct tgtaagctgt
           ccacaaaact tgtgtaatac tttagagttt gtcactttta aaagtttgta ataaatcatg
           gcttcataga acagttgaaa tttcacatcc gtagacgtta ataaagattt gaattatgaa
           gacactttct ggttatttta taattccatc tatctatatc tctgtactga agtgatcaaa
           acacttacga cacgttatct tggcttgtta ctcaaaaaat gaaaaaaata aactaaaaac
           gtgaacggca ggattcgaac ctgcgcgggc aaagcccaca tgatttctag tcatgcccga
           taaccactcc ggcacgtcca ctgtttgaga tgtaacttaa atattaagat aatataatta
           taaataaaga caacacgtta cgatactacg tggatagtaa ctaactattt gctgaattat
           gataaagtcg
4          ttcaacttta cctatcagtt tgttggatca atttattacc atccaattct cttgttatta
           ttcaaagttc aaacattccg ttccaatgtt aactttgtaa agtagtaaat ggtaagtaac
           aataactcta aatacctacc cttacaaatt aaaaattcaa cgcctacata aattatctac
           ctactagaat ttaaatatat aaaatcctag aataagtcaa caatcatatt aatgactaaa
           aattaccaaa actaaattat ttcattagtt taaaaaaaaa acaatttatt atattttata
           taatattata atgtttgcaa aaacagagta tcacgtcacc ttctctctct ctctatctct
           gtatcctctc attgcactat aagtactacc acaaccacga actctaaagc atcatctcat
           taacaaaaat aaaacacaca atctcaagat tttctacttc ttattacaaa gattcaatct
           tcttgtttct tcttgcaacc ATGAGTCTTC TTGCAGATCT TGTTAACCTT GACATCTCAG
           ACAACAGTGA AAAGATCATC GCTGAATACA TATGgttcgt cttcttcctc tgcttttgac
           catttgagtt tctctggttt tttctgttct tatcggaaaa caagagcttg agttaaagat
           ttgaatctta aagtcaatct tatcttaaag tcaatctttg tcatttacca ttttgtatta
           catctctaat ttggttttaa ttcaaatagG GTTGGTGGTT CTGGTATGGA CATGAGAAGC
           AAAGCCAGGg taatttaatc tttctttaac tataatttct ttgacaaatt gtaacttttc
           tcggagagat ttgattcgat tgaattacta agactctggt ttgttgcctg cagACTCTCC
           CTGGACCTGT GACCGATCCA TCAAAACTTC CAAAGTGGAA CTATGATGGT TCAAGCACTG
           GTCAAGCTCC TGGTCAAGAC AGTGAAGTGA TCTTATAgta agtctcttca agattaaaac
           caaaaaaaaa agtctcttca agattttctc taaagatcca tctcttttgt tttttgttta
           ctttcttaat aatatttgtt gtatttgtgt ttcttagCCC TCAAGCAATT TTCAAAGATC
           CATTCCGTAG AGGCAACAAC ATCCTTgtga gtttaaactt tttttttttt tttcttgcta
           tatgttctgt ttttagcggt taaagattaa cgttttttat cggtttgatc agGTTATGTG
           TGATGCTTAC ACTCCAGCGG GAGAGCCAAT CCCTACTAAC AAGCGACATG CTGCGGCTGA
           GATCTTTGCT AACCCTGATG TTATTGCTGA AGTGCCATGg ttaatccaaa ttcccctgtt
           ctttttatat agctttttcg ctttcttgcg gtggtcgtag atcgctgatt ttttttccgg
           ttaattagGT ATGGAATCGA ACAAGAATAC ACTTTGTTGC AGAAGGATGT GAACTGGCCT
           CTTGGATGGC CCATTGGTGG CTTCCCTGGC CCTCAGgtac attccgtttt tgcggagttt
           tttcgtttgt ttactgctct ttttcgattc tccgttcttg gcttctgaat tatctcttgc
           actcttgcag GGACCATACT ACTGCAGTAT TGGAGCTGAC AAATCTTTTG GAAGAGACAT
           TGTTGATGCT CACTACAAAG CCTCTTTGTA TGCTGGAATC AACATCAGTG GGATCAATGG
           AGAAGTCATG CCGGGACAAT GGGAGTTCCA AGTCGGCCCA TCGGTCGGTA TCTCAGCTGC
           TGATGAAATA TGGATCGCTC GTTACATTTT GGAGgtataa tttaaaacca ttcacttttc
           gattcttgtt gatctcttta aggaaatata aacttataac acaagttttg gtggttttaa
           aaacagAGGA TCACAGAGAT TGCTGGTGTG GTTGTATCTT TTGACCCAAA ACCTATTCCT
           GGTGACTGGA ATGGAGCTGG TGCTCACACC AATTACAGgt aaaaagaatc atgaatcttt
           tctcttgtta gatcattaca atgtttgtga gaacattcaa gaaaatggtg aacgttttta
           tttcagTACT AAATCAATGA GGGAAGAAGG AGGATACGAG ATAATCAAGA AGGCGATCGA
           GAAGCTTGGC TTGAGACACA AGGAACACAT TTCCGCTTAC GGTGAAGGAA ACGAGCGTCG
           TCTCACGGGA CACCATGAAA CTGCTGACAT CAACACTTTC CTTTGGgtaa agattttaga
           acattgtttt atttgtaaaa tgtttgataa cattttctga tctttgtgtt tgaatcttct
           ttaaaaagGG TGTTGCGAAC CGTGGTGCAT CGATCCGAGT AGGACGTGAC ACCGAGAAAG
           AAGGGAAGGG ATACTTTGAG GATAGGAGGC CAGCTTCAAA CATGGACCCT TACGTTGTTA
           CTTCCATGAT TGCAGAGACT ACACTCCTCT GGAACCCTTG Aaaggatgat ccgtaactct
           tgaagttgct tctgattggg ttttttggaa gttccaagct tgtcttttct ctacagtgtg
           tattaagcaa ttgtaccggt tgacactgcc ggagtttgtg atttggggcc tttctttctt
           tttcttcttt ttataatctt ttgggttctg tggttagagc aaattcggtt tgctctgttt
           gtttgacctt tattgaaacc tttggtattg gtactaataa tacaatctga aaaggcctct
           tcatgtttca atgttagaga ctaattaaag atctctttta tttttcattt tatacaaaca
           tgaaacacca atgttgatcc tgtctggtcc gtttttgatc tatgactcac aagatcgttg
           cgtactcata tcaacggctt tttgaacccc tttgtttgca aacaaaccac caatgtggga
           tgcttatcag tagaccgaac aaatgactac ttctccggaa ttttatttcc tttcaccttc
           c
5          taggactttt actatggtaa atcggtttag cacaatacac atgactttat gttattcatt
           cttcattcgt atatggataa aaaatcagcg atgctaaaca gatctcaata tgtatgtgaa
           cttgtgaagt agcaaattgt tgcttattcc actatattaa gtcaagtttc cacaatgtgc
           cagacaatcc ctagttgttt agattccaag atttcgacaa tgtaacaccc gttaataatt
           cacaacagct ctcttattgg caatatattc gataattatt aaatacataa atacaaaatc
           acattttgga atttaagaca ttttacaatt aaaaaaaaag tggaatcacg ttcaaaggtc
           gttgatagtc acaacttaac aatgacgcat taaagtattc aaaagtctat ttaactgatc
           tatgattgac acatagaaat gaagctatat aaaagttgta ctctcttttt gaaccatctc
           acaatcaaac tcaagtcaac ATGTATCAAA AATTTCAGAT CTCCGGCAAA ATTGTTAAGA
           CTTTGGGGCT AAAGATGAAA GTTCTGATAG CAGTCTCCTT TGGTTCCTTA CTATTTATAC
           TATCATACTC AAACAACTTT AACAACAAAC TTCTTGATGC TACAACCAAA Ggtaagaaaa
           ttatccatat cttgtgtttt attgttaagt caatgaatcc tcattttggt tttatgtttt
           cattttgttg tagTAGACAT AAAGGAAACC GAAAAACCGG TGGATAAACT TATAGGAGGG
           CTTTTAACTG CGGATTTTGA TGAAGGTTCT TGCTTGAGTA GGTATCATAA ATATTTCTTG
           TACCGCAAGC CATCCCCGTA CAAGCCTTCT GAATATCTAG TCTCTAAGCT CAGAAGCTAT
           GAGATGCTTC ACAAACGTTG TGGTCCAGAT ACAGAATATT ACAAAGAAGC AATAGAGAAA
           CTTAGTCGTG ATGATGCAAG CGAATCAAAT GGTGAATGCA GATACATTGT ATGGGTGGCA
           GGTTACGGGC TTGGAAACAG ATTACTTACT CTTGCTTCTG TTTTCCTCTA CGCTCTCTTG
           ACCGAGAGAA TCATTCTTGT CGACAACCGC AAGGATGTTA GTGATCTCTT ATGCGAGCCA
           TTTCCAGGTA CTTCATGGTT GCTTCCGCTT GACTTTCCAA TGCTGAATTA TACTTATGCT
           TGGGGCTACA ATAAGGAATA TCCTCGTTGT TACGGAACAA TGTCTGAAAA ACATTCCATC
           AACTCGACTT CAATCCCGCC GCATCTATAC ATGCATAACC TTCATGATTC AAGGGATAGT
           GATAAGCTGT TTGTATGCCA AAAGGATCAA AGTTTGATTG ACAAAGTCCC ATGGTTGATT
           GTTCAAGCCA ATGTTTACTT TGTTCCATCG TTATGGTTTA ATCCAACTTT CCAAACCGAA
           CTAGTTAAGC TGTTCCCGCA GAAAGAAACC GTCTTTCACC ACTTGGCTCG GTATCTTTTT
           CACCCTACAA ATGAAGTTTG GGATATGGTC ACTGACTACT ACCACGCTCA TTTGTCGAAA
           GCCGACGAGA GACTCGGGAT TCAAATAAGG GTTTTCGGCA AACCTGATGG ACGTTTCAAA
           CATGTCATTG ACCAGGTCAT ATCATGTACA CAAAGAGAGA AACTGTTACC TGAATTTGCT
           ACACCAGAGG AATCAAAAGT CAATATATCA AAAACCCCGA AACTCAAATC TGTTCTTGTC
           GCATCTCTCT ATCCAGAGTT CTCTGGCAAC TTAACTAACA TGTTTTCAAA GCGACCAAGT
           TCAACAGGAG AAATTGTTGA AGTTTATCAA CCAAGTGGAG AGAGAGTTCA GCAAACAGAC
           AAGAAAAGTC ACGACCAAAA GGCGCTTGCT GAGATGTATC TTTTGAGCTT AACCGATAAC
           ATTGTCACGA GCGCAAGGTC TACATTTGGA TATGTTTCAT ATAGTCTTGG AGGATTAAAG
           CCATGGTTAC TTTATCAGCC AACAAATTTC ACCACTCCTA ATCCGCCATG TGTTCGATCT
           AAGTCGATGG AGCCATGTTA CCTAACTCCT CCGTCTCATG GATGTGAAGC TGACTGGGGA
           ACTAACTCGG GGAAGATTCT TCCTTTTGTT AGGCATTGTG AGGATCTTAT ATATGGGGGG
           CTTAAGCTAT ATGATGAATT TTAGttctat tttatcacat ttgattttat tggattattg
           agtttttata atctaaggaa aaaatgctat ccgatccctc tttacagttt acacttgtgt
           cctcttctta tgtattaata tgttagtttt cttaaaacgt ttactaggtt tgtatggttt
           ataatattaa ataaaatgaa atttacatat atacttgtat cacttaaaat cattaagact
           ctaatttaat ttatatcatt gtgatgtttt ctcgaggtta ctttatgtgt catgaagata
           atggagtatt ggagttgtga ggtatcatgc gtcgtcgttg ttctactcta gtccaccttt
           aaagaatata aaaagagata tttaatcaat gttatgcgtt acaacatttt attatcgaaa
           aaacgttttg agtataaaag aaaaaataga gaaattttag tgatttccga gatataatat
           tcacctgcaa aagagagtgc tgattttaca caaatattga gagc
6          atcttccaat ataaagtctg aagcgcgggg tagtggagat ttgaacaatg gagtacataa
           aatagttcgg accccacctg tctttgatgg gaccatgcgc gcaaagcgct ctttcctctt
           ggatgatgcg tctgatggta atgaatctgg aacggaagag gatcaatctg cttttatgaa
           agaattggat agttttttta gagagcgaaa catggatttc aaacctccaa aattttacgg
           ggagggcatg aactgcctca agtaagcttg atacccatca ttatttggtc actttactgt
           gttacatttt aaaattttca gcaggagctg atatctaatc aatttctttg gcacaaggtt
           gtggagagct gtaactagat tgggcggata tgacaaggta cgggtcactg tgaatacgcc
           tgttgaatgt cacagcatct tttttgacaa gcaaatgtga cttcggcttt tcatcttttg
           ttccatcctg gcttacttgc ATGCGTACTG TTGTTCATGA TCTAGCAGTG GTGCTTTTGG
           TGATTTTCTA TGATTATTAT ATGCTTTTTA TACTGGATAG GTTACTGGAA GCAAATTATG
           GCGGCAAGTG GGAGAgtctt tcaggccccc aaagtaagaa gaatgctttt cttattagtg
           gtttgtctta gAAATTTTGG GAAATCATGT GGATATTTTT AAGAATTACC CTCTAATTGG
           TCAATTGTTT GTTCAGGACA TGTACAACAG TATCATGGAC TTTCCGAGgt ttctacgaaa
           aggtgagact atattcacca ccttttcctc tctctgcttt tggttcgtct atgtgacttt
           tgtatacact ggcatgggac tgggactcta tgtatcaacc cttctgagaa ataattgaaa
           tgattgaaca gtgaacaact gtgaatcatc ttgagatatg ttttccttaa gatacagtaa
           catcttgtaa cattatagTT TCTTCATTTT TCAGGCTCTT CTTGAATATG AGCGGCATAA
           AGTTAGTGAA GGTGAACTTC AGATACCCCT TCCGTTGGAA CTAGAACCGA TGAATATTGA
           TAATCAGgta aaattgagaa aaccatatca tgtgtctgta gtttttgttt gatcttcttc
           ttctgattaa tgtcagtgtt ttaacttaac ccactgcctt gtttctacac tagGCGTCTG
           GATCAGGGAG AGCAAGGAGA GATGCAGCAT CACGTGCTAT GCAAGGTTGG CATTCACAGC
           GTCTTAATGG TAACGGTGAA GTTAGTGACC CTGCAATCAA Ggtccggtag aatcttttta
           tatgtttcat tttacattca cactagatct ctcgtttttt ttttgtcaaa catttaatct
           atatctcata gtctgaacga acatactgtt ttgtaattaa tagGATAAGA ACTTAGTTCT
           TCATCAAAAG CGCGAAAAAC AGATTGGAAC CACCCCTGgt atgagttctg tttgatgaag
           aagtgttgtt ctcattttta ttttgaaact ttgacatggg ttatcactta catctcacaa
           tgtcatcagG TTTGCTCAAA CGTAAGAGGG CTGCTGAACA TGGTGCAAAA AATGCCATCC
           ATGTATCTAA ATCTATgtac gatttttggc tttgtggtct ggttttcaat gcgtgataat
           tcacatttga attctgattc cagttgttgt ttttcctagG TTGGATGTGA CTGTTGTTGA
           TGTTGGACCA CCAGCTGACT GGGTGAAGAT TAACGTACAG AGAACGgtaa aatcaattgc
           cactttctta aaaacctgag caatcacttt ctggttttac atatattaat aaactcttcc
           actatctgca gCAAGATTGC TTTGAGGTGT ATGCATTAGT CCCAGGATTA GTCCGTGAAG
           AGgtaagctc tcaaatctcg ttgtgtttac atatggatcc taagattgag tttagcactc
           agtttttgtc ttggcaacaa taatacagGT CCGAGTCCAA TCAGATCCGG CTGGGCGGTT
           AGTAATAAGT GGCGAACCCG AGAACCCTAT GAATCCTTGG GGAGCTACTC CTTTCAAAAA
           Ggtaaatgct ggttacatga tttttcagct tacacgtaga atgttgaatg acattttcaa
           acctccattg aaactgcagG TGGTAAGTTT ACCAACGAGA ATCGATCCGC ATCACACATC
           GGCTGTGGTA ACCCTAAACG GGCAGTTATT TGTTCGTGTG CCTCTGGAGC AATTGGAGTA
           Gaaacattta cagtttaaca aagcctttga agatctgaaa gagagaagat tgttagaagt
           agttgttgag agtattttgt ttgtatatta tgagagatta agcacaacat gagaagagcc
           tttaggaatc cttaattagg ccatctagtt tttattgtct ctcctctctt tgattagatt
           cttcttctaa gtgtcatcac tattgatttg ttgtagcacc aaacttcttt aaacctttct
           attaagaaca cacaaatcta caaccttttt atttttttta attgtttatg tgatttgttt
           tctgtggcag tgaatttttt atattatcaa cttatcatgt tagctcaaga ttgcatctca
           atttgtactt atcttagtgg taattagaaa aaaaaacaaa attaggctac aatagttttg
           tttgtttgtt tgtttaggtg ttagggatag ggtttatttt ttccgaagtt tattagtgtt
           tactatttag agtttaatgt t
7          gaaagtatta tgataaagaa ggattaaaaa aaaaaaaatc ttcttaatat agcttacaat
           gttttgttgt taaagtatag ctaagtaaag tatgttataa atggtgcatg attttttatt
           tttgattaaa aagtggtaaa tgatattttt ttcctccatt ttgcattttt acactttgta
           tgatccaatt tgcttttatt tatctacata taataaatct ctataataaa ccatttacat
           accattacta aaactaaaat tataatggaa aaatattatt atgttattta ttgttacttt
           ggtaaagcat tattatttat tttgcttatt ttaagggcta ataattaatt gaaattaagc
           agttgacgaa agtttttttt attaatttat aaagcacaac atttccttgt ctacacgatc
           ataaagctca caaagagaga attgagaaga aacaaactcg tcggagaatt cagtactcgc
           cgaagaggaa gaagaagaag ATGTCTTGGC AATCATACGT CGATGATCAC CTTATGTGTG
           ATGTCGAAGG CAACCATCTC ACCGCCGCCG CAATTCTCGG CCAAGACGGC AGTGTCTGGG
           CTCAGAGCGC CAAATTTCCT CAGgtttttt tacttcttca tcctctcttt tcgccttact
           acgatccgtc gcttgaattg tcggaatcct ccgtgatcgg atctgacgaa tctcggatct
           gattttgaat ttttcaatct ccggaatctg atgaatattt tcgatttgca tttctaaatc
           tatcgatccg tatgcgaaat tgaattcaaa cgtagggctc tagaccatta gtctattgtg
           agatttcttc ggtatcagaa gttattagat cgtagcttcc atagaagaag atccatatgc
           ttgtgaaatt gtacgcatgc gtgtgcaacc atcgatgcaa ggtcttcttc ttcttgtagg
           catgtagatt ctatggtctt agtcagaatt actgcttaac aattgcatct tggataatct
           ctgtttccat ttttcttata tgcttgagga aatgttttga tcaatagcct aaaatgttga
           tttgattttg ccaaaatctg atgatgtgtt attgataatg tgtgtttagT TGAAGCCTCA
           AGAAATCGAT GGAATCAAGA AGGACTTTGA GGAGCCCGGG TTTCTTGCCC CAACCGGACT
           ATTTCTCGGT GGCGAAAAAT ACATGGTTAT CCAAGGTGAA CAAGGAGCTG TGATCCGAGG
           GAAGAAGgta actttcttta cttcatacat cagaaagctg catgtagatt ttgatagaga
           atagaatcgg aattcatgta acaatctgtg aatcttcagG GACCTGGAGG TGTCACTATC
           AAGAAGACAA ACCAAGCTTT GGTCTTTGGC TTCTACGATG AACCAATGAC TGGAGGTCAA
           TGCAACTTGG TTGTCGAAAG GCTCGGGGAT TACCTTATCG AGTCTGAACT CTAAaaccaa
           ggtttcattt caggttcttc ttaactaaag agtgtcaatg cactttttat tgtgattgat
           tgtaatgctt tcaaacacaa atcatttgtt actttagaac caattgtgat tgattggtct
           ccttcgttac cgagtttgag tttgtgtgtt cttgtaatga catttgatca tcttttttct
           ccatatgtat tgagttttga tttttgtttc ttcatattat tactttttct tgaaatgatc
           tgctgtttat gatttggggt tcaaaatatt tttggtttgg caaacaagga agagtttgcc
           aagtattagt agcaagtgct atgagtattt tcggcttggc gaacatcttc gtgtacacgt
           gtgacataac aaacctattt gagaatggtg taagctaggt agatattaca taaacgatgt
           aagttgggaa ttcgtttagg agagagatat tgtatggtaa gaatttcact tcgaattctc
           tgcttcaacg tggc
8          agaagactag gcggaacatc tcatcaaaac cctatacatt caacagggaa attcttttgc
           acgaatgtta gacttcaata ttgaataaaa ttcatagttt caacaatctc ataaaaaaag
           agctgggctc cattcgaaga cacattaatt tccatgggcc tggtccacat acaaccatac
           taaatttgaa gtaatttacc cgccatttaa aaaagcccat aggctccttc tcctagaagc
           tggcgggaaa atcccaaaac ttttcccggg aaagtagata aaaaatttcg gccattaaag
           gacaaaatca caagaaagta gaaaccctag agattttgaa accgaaaccc caaaaacccc
           tttgacgcct ccttgttctt atctctttat aaaaaaccat ttctttcctg caacatcgtt
           gcttatcatc agacgcacat cacctgttcg ataaaattcc tctgagagtg ttttttttgt
           tttccttctg acaaagaaat ATGTATGTAG TGAAGCGTGA CGGAAGACAG GAAACTGTTC
           ATTTCGATAA GATTACTGCG AGGCTTAAGA AACTTAGCTA TGGGCTTAGC AGTGACCATT
           GTGACCCTGT CCTCGTTGCT CAGAAGGTCT GTGCCGGTGT CTATAAAGGA GTCACTACGA
           GTCAACTTGA TGAGTTGGCT GCTGAAACTG CTGCTGCTAT GACTTGTAAC CATCCTGATT
           ATGCATCTgt gagtatctct cttcgttttc ctttctgggt attgcttgat tttgattagt
           cgtttctgga gaagtgatct ctgtcattgg attggtgttt catttgattg aattgatctg
           tataatttac atgttatctg tgttcatatg tcagCTTGCT GCTAGGATTG CTGTGTCGAA
           TCTCCACAAG AACACTAAGA AGTCATTTTC TGAGACgtga gtgttgagtt ctttcttagt
           gtgtattata cccttgatat gagttcaagt ttccatgtgt gttgactccg atggcttgtg
           tggtatcttg cagGATTAAG GATATGTTCT ATCATGTCAA TGATAGATCT GGACTAAAGT
           CCCCACTAAT AGCCGATGAT GTGTTTGAGA TAATTATGCA Ggtaaagaaa tcttgtgtta
           agctcttgat tcaatctgtt tcttggtgtg atatatatat atatatatat gtatgtatct
           tataaatcac tgacttgtgt gttactggtt tcttcagAAC GCTGCTCGTT TGGACAGTGA
           GATCATCTAT GACCGTGATT TTGAATATGA TTACTTTGGA TTTAAAACTC TTGAGAGATC
           GTACCTCTTG AAAGTCCAAG GGACTGTTGT TGAAAGGCCT CAACACATGC TGATGAGGGT
           TGCTGTTGGG ATCCACAAGG ATGATATTGA TTCCGTGATC CAAACCTACC ATTTGATGTC
           TCAGAGATGG TTCACTCATG CATCTCCTAC TCTCTTCAAC GCAGGAACTC CAAGGCCTCA
           Agtaaatacc tatcacttga tatttattat atctattaaa taaggcgttt tactttgata
           cgtgtctttg ctgatctgct attgaaaata attgaaattg cagTTAAGTA GCTGCTTTCT
           AGTCTGCATG AAAGATGATA GCATTGAGGG CATATATGAA ACACTCAAAG AGTGTGCTGT
           TATAAGCAAA TCTGCTGGGG GTATTGGTGT TTCAGTTCAT AATATTCGTG CTACCGGAAG
           TTACATTCGT GGCACAAATG GAACATCTAA TGGTATTGTT CCTATGCTGC GTGTATTCAA
           CGATACAGCT CGTTATGTTG ACCAAGGAGG AGGCAAGAGA AAGGgtacgt atcagctctt
           tgtactatta gcataatcat ctgtccagta tatggtctaa agtgtatctg atttataatt
           tgtaattggt gaagGAGCCT TTGCTGTTTA CCTGGAGCCA TGGCATGCTG ATGTCTATGA
           GTTTCTGGAG CTGCGAAAGA ACCATGGAAA Ggtatagtca tagctagata attcaccata
           tctactccct aaatgtgatt accatttgac gctgatacaa cctcttaata cactttgtcg
           cattgcagGA AGAACACAGG GCTAGAGATT TGTTTTATGC TCTCTGGCTT CCAGATCTTT
           TCATGGAGAG GGTCCAGAAT AATGGGCAGT GGTCACTGTT TTGTCCTAAC GAAGCTCCAG
           GTTTGGCAGA TTGCTGGGGA GCTGAATTTG AGACACTGTA CACTAAGTAT GAAAGAGAGg
           tgagtcccta tttcatccat gtatatgctg cttctttagt aactcaaatt cctgttatct
           caatacagtt atgtttgttc atatcttcag GGAAAGGCCA AAAAGGTTGT TCAGGCGCAG
           CAGCTTTGGT ACGAAATATT GACATCCCAG GTAGAAACAG GAACACCATA CATGCTTTTC
           AAGgtaagta acagtcatca ttctgtagct acacgttatg gccttataat cattggttct
           tactccaaat ttgaatgctc ttaaactata gGATTCATGC AACCGAAAAA GTAATCAGCA
           AAATCTGGGT ACCATAAAGT CGTCCAACTT ATGCACTGAA ATCATTGAGT ACACTAGTCC
           AACAGAAACT GCTGTGTGCA ATCTTGCATC TATTGCTTTA CCCAGATTTG TAAGGGAGAA
           Ggtgagaggg agactggttt tttaaaattt gctttctctt tattactcaa tgtatagctc
           taacattctt catctcacaa cagGGTGTCC CATTAGACTC TCATCCACCT AAGCTCGCTG
           GCAGTCTGGA CTCAAAGAAT CGTTACTTTG ATTTTGAAAA ATTAGCAGAG gtcagataca
           agcactcgcc ttgcttgacc tgaaatctga ttcttaagga attatctgtg gagatatttc
           cgtgtctgtg atgtgatgtt tgacttttta atttttctgt gtggccagGT GACTGCTACT
           GTTACTGTTA ATCTCAATAA GATAATAGAT GTGAATTACT ATCCTGTGGA GACTGCAAAA
           ACTTCAAACA TGCGTCATAG ACCTATTGGT ATTGGTGTAC AAGGCCTTGC AGATGCATTT
           ATCCTCCTTG GAATGCCATT TGATTCTCCA GAGgtagact tgttttgaat tatgatcaat
           cttggaaaat ataattttgt tatctgttct taagcagttt aatttgttac tcagGCCCAA
           CAACTGAATA AGGATATATT CGAAACCATA TACTACCATG CACTCAAAGC ATCTACAGAG
           CTTGCTGCAA GACTTGGCCC CTATGAAACC TATGCTGGAA GTCCCGTGAG TAAGgtatgc
           atctcagcca tcaattatat caatttggtt ttcccaaact tcataagcta ccattgtgga
           ttgttatgct gactttatcc catgcttctc tagGGAATCC TTCAACCTGA CATGTGGAAT
           GTAATTCCAT CAGACCGCTG GGACTGGGCT GTTCTTAGAG ATATGATATC AAAGAATGGA
           GTGAGGAACT CTCTTTTAGT AGCACCAATG CCAACTGCTT CAACCAGTCA AATCCTTGGG
           AACAATGAAT GTTTTGAGCC CTACACATCA AACATCTACA GCCGCAGAGT CTTGAGgtat
           gtgaatatta aatcatttga caagtatgtt tctggttttc cccatttgat gcttactcac
           ttggttgtct tggtttgtac agTGGTGAAT TCGTAGTGGT TAATAAGCAT CTTCTCCATG
           ACCTAACTGA TATGGGACTT TGGACTCCAA CGCTGAAAAA CAAATTAATT AATGAGAATG
           GTTCTATAGT TAATGTTGCT GAGATACCTG ATGACTTGAA GGCGATTTAC AGgtatagct
           tccacttatt ttgtgttttc actctctact gtctagataa agaaatttga cttgtttctt
           ctgtaaaaca acacagAACT GTCTGGGAAA TCAAACAGAG AACAGTGGTG GACATGGCTG
           CTGATCGTGG ATGCTACATA GATCAAAGCC AAAGCTTAAA CATACACATG GACAAACCCA
           ACTTCGCAAA ACTCACTTCG CTACACTTCT ATACTTGGAA AAAGgtacaa accttaatca
           tctaaactct tcatatgata attgtgaaat aggttagaga ttctatagag tatctgatcc
           ttcactcatc tgacaattac tcttaatctc acttatgttg ttgtgaatct accttaagGG
           TCTGAAAACC GGGATGTACT ACCTGCGATC CCGTGCTGCA GCTGATGCGA TAAAGTTCAC
           CGTTGACACA GCCATGCTCA AGgtagaaaa aacaatgcaa actctttacg ctgattcttc
           ttgtgaactc agacatttta cctatgagtt gttttcgttg gggtgaatgt agGAGAAGCC
           GAGTGTAGCA GAAGGAGACA AAGAAGTAGA AGAAGAGGAT AATGAAACTA AGTTGGCGCA
           GATGGTATGT TCCTTGACAA ACCCTGAAGA GTGTTTGGCC TGCGGAAGTT GAagctctaa
           gttatagttt gggtcttaaa aagttagaaa gtaaaagcat gtctcttgga cggtcttttt
           tatttacttg cttatctggg tgtattttgt taatagtttc ctaatgctta atgttgcttg
           agtttttgtg taatccaatt tcgtttttac cttttctctt gaaacaataa ggatttgtaa
           cgagaattat gtataaccac caccacctta cggtagattt tactatccat atataaatat
           tttaccatcc atttataaat atttgtagtt tggtactact accaatggtt gtaagtaatc
           tgtaagaata tattctgatc attgtagatt agaaaatgtg ttactacagg tttcactagc
           ttatcctaga actagaaaca tgaaaattat gtatcgaatg gtgaaaatat taatacaaac
           atatttacgt ttaaatgcat gtgtacacaa caaagtttct aaagcaagct ctatcatata
           gagaataaag ta
9          ttgctttagg tatccatata gttttgaccg acctcgatga tcatgttata ttctgtggag
           atttatcaac tatttataaa taccttgaaa ccgctactag acattggagt aatccctcac
           cttgtctcat ttggcaaata tttcctatag gttcaactta ttagtagaaa tgacaatgtc
           ttggctgaca cttatcaaga actctccttg taatcactta gttacttcca ttatggaaaa
           gttgaccgat cgaaaaaagg tattaaaaaa aaaaaataga aaaattaaga ttttcatagt
           gtaattgtaa aaaataaaat caaattattt tcagatattc cgtattggga ataaatctca
           gccgttgatt actatcaacg gtgtacaatt actgcctttg cctgttactt gttctgctcc
           gtcgctcaga taggatctca acaagacacc acaaacccta aatttcgtca actccacagc
           gactcgattc gatcaaggaa ATGGCGTACG CTTCTCGTTT TCTCTCCAGA TCTAAGCAGg
           tatatactct ctctccctcg atttttctga ttctcttctt cgttctgttt gattcctttt
           gttttcctcc catttctggg ttttatgtgt ttcgatgcga tggttagagt gagattatcg
           attttactgt atctctatca ctgaatcaca tcttagggtg tgccatttca atatcgtagt
           cgaatttttg ttatctttcg tacgatctca atcggagagt ttgttgaaat caaatgataa
           atttgatggg gtttttttct actcgttgtt gatttctaat acagttcgaa atgataagat
           gatttgcaag aagtattctt ttcatcaaaa cttgttattg atccataatt tttattatct
           tactctcatt acgcagCTAC AGGGGGGTCT GGTCATTTTG CAGCAGCAAC ATGCTATTCC
           AGTCCGAGCT TTTGCTAAGG AAGCTGCTCG TCCAACCTTT AAAGGAGATG gttagtgacc
           aaaactcata cttcggattt gttattatgc atagaacatt acgttttcaa taacacacct
           agttgaaaac agttgctttc ctttctttag cccttcgtgc ttttgagttt aacatcgtga
           ctacttaaga atatgtcaag tcactttttt tatgtcgaat gtgtagaaaa actatattgg
           tcaatgtaat ataatcttgt gaaacccagg ccatgattgc taggactgtt gttctgctta
           cttcttttgt tgagttttat atgtatccag tttatgatgg attatgttta atatgttgct
           gaaatctgta ctatgtgttt agagtgaaga agcattgctg tttactatta ttgactcaag
           ttttacactt tttgacagAG ATGTTGAAGG GTGTCTTTTT TGATATCAAG AACAAATTCC
           AGGCTGCTGT TGATATTCTC CGTAAGGAAA AGATCACCCT TGATCCAGAG GACCCAGCTG
           CCGTAAAACA GTATGCAAAT GTAATGAAGA CCATCAGGCA AAAgtaggcc tcttgttact
           cttttgtagg tgtttgttat ttagcttgaa tcttgtatgt cgtgatctct atttctgttt
           gttgggattg gttttacttt tcgacttttc tgaaacgagt taaatatatg tgtcaatgct
           gctattttaa ccttgttaat ttggttgctt gtcatccgtt tttttggtat gcagGGCAGA
           CATGTTCTCA GAATCTCAGC GCATTAAACA TGACATTGAT ACTGAGACTC AAGACATTCC
           AGATGCTCGT GCATACTTGT TGAAGTTGCA GGAAATTCGC ACCAGgtagc tgttagactt
           tgaataattt tcagttatct taggatagtt ttccctcacc cgtaaacttg ctcttcttat
           gttattataa tattggaatt atcttcctgt aagatcttga atgtgatcgt taagcagtta
           tctgaagact gcatttaact atctatattt tcatctccct ctttgatctg ctattgtttg
           caacatatga agaattgttg gaagcagtct ttagttatac tcccacttgt gatatatctt
           gcagGAGGGG GCTTACTGAT GAGCTTGGTG CTGAGGCCAT GATGTTCGAG GCTTTGGAGA
           AAGTCGAGAA GGACATAAAG AAGCCTCTCC TGAGAAGTGA CAAGAAAGGA ATGGATCTTT
           TGGTTGCAGA GTTTGAGAAA GGCAACAAAA Agtgcgtcat cattcttcaa ccatccatac
           aaaacacgaa caaatgattc tcattactac ttatatgtat atcgatttac atattgatag
           ctaattgaat tgcatgtttg cgtctcatta atctaaacag GCTTGGGATT AGGAAAGAAG
           ATCTTCCTAA GTACGAAGAA AATTTGGAGC TCAGCATGGC CAAAGCACAG TTGGATGAGC
           TGAAGAGTGA TGCTGTTGAA GCTATGGAAT CTCAGAAAAA GAAgtgagtt ttgttttctt
           ttcacttttt ttgtttctca atttatcaat cattgatctt actcatgtca taacgcgatg
           gaacttgcgg attattcagG GAGGAATTCC AGGATGAGGA AATGCCGGAC GTGAAGTCTC
           TAGACATCCG TAACTTCATC TAAggtttga tccttagaaa catttgattt gttgtaagaa
           aaggcaaaga tctctcactt gattgtcttt gaaagagaag atcgttccct tgctgctgtt
           ttggtttggc gttcaataag gtctctcacc tggatttgag tctaactctc tctgtggtta
           ttacgcttga gattcttaga cacaaacgtt gtttcatgtt tttttgataa tggtgatcac
           tggaatttga gataattaat aaaagttgtg atgttaattc gaaacaaaag cgtggcaagc
           aaaatcaacc cgagaaacta ttatagtttt gtatttagta gaccaaattc gaaccaaatc
           taaccgaaat gggatctgga gtatcataca ttctagatga attaaaccaa tcatatcgaa
           cacgtggctt gtctgtgaac aattataatg ggtttgtctg agagacgtta acaactgttt
           tcttcgccat ggcggcgatt cctctcaaag ctccttctct tcc
10         tttcgatcag ctttttcgat tttggatcta ttttctatga aatatcagat ctggtgattg
           ttttacatat ttttgggttg aattcacaag attttctgga aacgagatcg attaattgag
           ttttctgtgt ttttatctta agctagatct cgatttctat gtttttggat tgatttgata
           agattttcga gaattttttg tgtttttgtc aaagttcgat ctcgatttct atatttttgg
           ttgaattcac aagactttct ggaaacgaga tcgattttgt gagttttctt tgtttttaat
           ctcgattttt ggattgattt gagaagattt tctgaaagcg agatcgatgt ttttggggat
           tttctttgtt ttgttcaata attcggtctc tgttttctta tcaaaaaatt cgttttccat
           ctcaaatcga tgttcttatt gatttaattg agttttagtt tgcagggatt tgatcgttgg
           taagctatct ttcagcaaac ATGCATGGTT ATGAAGATgt aagcacgctc atgaattttt
           gttttcagtg attttgtcga attcaattta aggtagatag atttgacatt gttcgataat
           gttatattgc agGACCTTGA TGAGGAAGCT GGGTATGATG ACTATTACAG CGGTGATGAG
           GATGAGTATG AAGATGAGGA AGAGGAGGAT GAAGAACCTC CTAAGGAAGA ATTGGAATTT
           CTTGAGTCAC GCCAAAAGTT GAAGGAATCA ATTCGGAAGA AAATGGGAAA TCGAAGTGCT
           AATGCTCAAT CTTCACAAGA GAGAAGAAGA AAACTTCCTT ATAACGAgta tgtggtggct
           aaatcacatt ttctaattca ttacaatgtc ctggaatgtg ttttgatgct gagcttattg
           atttttctta atgcagCTTT GGTTCTTTCT TTGGTCCTTC ACGGCCTGTT ATTTCCTCAA
           GGGTTATACA AGAAAGCAAA TCCTTGCTTG AAAACGAGCT ACGTAAAATG TCGAATTCGA
           GCCAAACTgt atgtgcattt gatctttgtt actctttgta tttttatcat ttaagATGTT
           TTTGCTGATG GAATTGTTTT TTGGGGTGCA GAAGAAAAGA CCAGTTCCGA CGAATGGTTC
           AGGCTCTAAG AATGTGTCAC AAGAGAAGCG ACCTAAAGTT GTGAATGAGG TGAGAAGGAA
           AGTTGAGACT CTTAAGGATA CAAGAGACTA TTCGTTTTTG TTTTCCGATG ACGCGGAGCT
           TCCTGTTCCG AAGAAGGAAT CTCTTTCACG AAGTGGCTCT TTTCCTAATT CTGgtatgtt
           gtgtcttttg aaaaatcttt ttcgctattt gtgatcttta agCATACCAT TTTCATGAAG
           ATAACTTATA CAGGTTTTTT GCTGATGTTC AAGAGGCTCG ATCTGCTCAA TTATCATCGA
           GGCCCAAACA ATCATCAGGT ATCAATGGTA GAACTGCTCA CAGTCCCCAT CGTGAGGAGA
           AGAGACCTGT TTCAGCGAAT GGACATTCAA GACCGTCTTC CTCGGGCAGT CAAATGAATC
           ATTCAAGACC GTCTTCCTCT GGCAGTAAAA TGAATCATTC AAGACCGGCT ACCTCGGGCA
           GCCAAATGCC AAATTCAAGA CCAGCTTCCT CTGGCAGCCA AATGCAGTCG AGAGCTGTCT
           CAGGCTCAGG GCGACCTGCT TCCTCAGGCA GCCAGATGCA AAATTCAAGA CCACAAAATT
           CAAGACCAGC TTCCGCTGGT AGCCAAATGC AGCAAAGGCC TGCGTCCTCA CGCAGCCAAA
           GGCCTGCGTC CTCAGGCAGC CAAAGGCCTG CGTCCTCAGG CAGCCAAAGG CCAGGTTCGT
           CGACAAACCG TCAAGCACCT ATGAGGCCAC CAGGTTCAGG TTCCACAATG AATGGTCAAT
           CAGCCAACCG GAATGGCCAA CTGAATTCCA GATCAGATTC CCGAAGATCA GCTCCTGCTA
           AAGTGCCAGT GGATCATAGG AAACAGATGA GCAGTAGCAA TGGAGTTGGT CCTGGTCGGT
           CAGCGACCAA TGCAAGACCT TTACCTTCTA AGAGTTCATT GGAAAGAAAA CCCTCAATCT
           CGGCGGGAAA GAGTTCTCTT CAAAGCCCTC AGAGACCGTC CTCATCAAGA CCAATGTCAT
           CTGATCCTAG GCAACGGGTA GTAGAACAGA GAAAGGTTTC TCGTGACATG GCCACACCCC
           GAATGATACC TAAACAATCA GCGCCTACCT CGAAACACCA Ggtatcatga tcatgatctt
           tcacatctct ttcttttgtc cttcctctag ccaaggcact aatttgtcaa gtaatattta
           cagATGATGA GTAAACCAGC GCTCAAGAGA CCTCCCTCGC GTGACATAGA TCATGAAAGG
           AGGCTGTTGA AGAAGAAGAA GCCTGCAAGG TCAGAGGATC AAGAAGCATT CGATATGCTT
           AGACAGTTAT Tgtaagtatt gctccaaact ttcttcctac tctcaaattg taagttacaa
           ttttctaatt ctattttgtc tcctgatact taaatggggg tttgtgtatc aattttagAC
           CACCCAAGCG GTTTTCTCGG TATGACGATG ATGACATAAA CATGGAAGCA GGCTTTGAAG
           ATATCCAAAA GGAAGAGAGA CGAAGgtaca tgagtatttt tgttatcaca cgtttcattt
           atttgtgttt cttggatatt ccttaacgat tgaattggtt gttaaatgca gTGCGAGAAT
           CGCAAGGGAG GAAGATGAAA GAGAACTTAA GCTCTTAGAG GAAGAAGAAA GGAGAGAAAG
           ACTGAAAAAG AATCGGAAGC TGAGCCGTTA Gaagaatcct ttctcctttg tgtctttgtc
           ttcttttagg acttttttag tgttttctca ttgaaatctc tttggccgct tgaggcaaaa
           aagagtttga cctttttttt gttttgtgtt ttcaaattaa ggatcttttt tttgttcatg
           gaaattgtac aattagaaat aatatctttt attggggaca cttcaagaag aatctgttgg
           aaaccttccc agttagtgaa agcttgattc tctttttttt ttttggagta aagctaaaac
           cagaggagga tgataaagaa aaagaaacaa agaatatttc tttattcacg tgtagagttc
           ctttagctga taaaatttca ctttttatga gtctgataac atgattttag tgattctttg
           tctcttttat tctttggcta aacaaattcg ttgagaaatc aaatggtgac caaagaagaa
           gattgccttc ctcctgtaac ggagaccacg tcgagatgtt attctacttc t
11         ataccggaaa tgtcgtaccg tcctgaacat aatgcacata atttgactgt agctaggctg
           taaaagattt taacaaaatt gttttagaat aaaattataa gtttaaaagg tatggtttga
           cttgaactgt actggaattt ataccggaaa tatcgtaccg ttctgaacat aatgcacata
           atttgactgt agttaagcag taaaagattt taacaaaatt gttttaaaat aaaattataa
           gtttaaaagg tatggtttga cttgaactgt accggaattt ataccggaaa tgtcgtaccg
           tcttccacac ttcggagaaa cgacagataa gctctctctg ttctcttgcc acacttccca
           atacatggat ccattttgac gtcatcttta tcactatctc tctattatat aaatctcttc
           gtaccctttt accgattctt caccgtgatc gcttaatcag acctcaattt cgttgttaaa
           gaacaaagct ttaagcagcc ATGGATCCAA ACCAACGTAT CGCGAGAATC TCTGCTCATC
           TCAATCCTCC TAATCTTCAT AATCAGgttc aaatttcgtt gaattctctg attcttaaac
           caatttggtg atcgaagttt gattcttttt tttttgggtt gatctgattt cgatgatttg
           gatttagATT GCTGACGGGT CAGGTTTGAA TCGGGTGGCT TGTCGGGCAA AAGGTGGATC
           ACCCGGATTC AAAGTGGCGA TACTTGGAGC AGCTGGTGGA ATTGGACAAC CTCTTGCGAT
           GTTGATGAAG ATGAATCCTT TGGTTTCGGT TCTTCATCTC TATGATGTTG CTAATGCTCC
           TGGTGTTACT GCTGATATTA GTCATATGGA TACTAGTGCC GTTgtaagtt ctaaattctc
           cggttttcga ttccaaaatt actactttag atgttttaga gctaataaaa ttgatcaata
           gtgatgattg ttgttgttga aatagagaaa tgagcttaaa gatcatatac atgagcttaa
           aaactagtac tttagatgtt gtagagcact agtgatgatt gttgttgtta agatcatata
           gagattgttg tgaatgtttt tggaaaactt tgttttagGT TCGTGGATTT CTCGGGCAGC
           CGCAGTTAGA GGAAGCACTT ACGGGTATGG ATTTAGTGAT CATACCTGCT GGTGTTCCGA
           GGAAACCAGG GATGACGAGG GATGATCTGT TTAACATTAA TGCTGGGATT GTGAGGACAC
           TCTCTGAAGC TATAGCTAAA TGTTGTCCTA AAGCAATTGT GAATATAATC AGTAATCCGG
           TGAACTCCAC GGTGCCAATC GCAGCTGAGG TTTTCAAGAA AGCTGGAACC TTTGATCCAA
           AGAAACTCAT GGGTGTCACT ATGCTTGATG TTGTTAGAGC TAATACCTTT GTGgtatgca
           ctcattattt ggtcttagaa tggtgtttag tattgtccat tagaactcaa ctatcttctt
           ctttgcattt atggggttga atagGCGGAA GTAATGAGTC TTGATCCCCG TGAAGTTGAA
           GTTCCGGTTG TTGGAGGACA CGCAGGAGTT ACGATTTTAC CACTGCTTTC GCAGgtttga
           gatcagatga ttctcatcat tatgtttgtt tgaagcagat ataatattct catcattatg
           ttggctacag GTGAAACCTC CTTGCTCGTT CACTCAAAAA GAGATTGAAT ATCTCACAGA
           CCGCATCCAA AACGGTGGCA CTGAAGTTGT TGAGgtataa actaatcttt cagctttctt
           tgttttgaac ttcgaattaa gcggtgcatt taccgtttaa atcattttgc agGCTAAAGC
           TGGAGCAGGT TCTGCAACAC TATCCATGgt aggtcttttg ttgtaacatg ggagttgtat
           gacaaagctg ggaatttgat tgatatctca atctgttaaa tgataaaata cagGCATATG
           CAGCAGTGGA GTTTGCAGAT GCTTGCCTCA GGGGTCTACG AGGTGATGCA AACATCGTTG
           AGTGCGCATA TGTGGCATCC CATgtacagt cctttaattc aactgtacaa tattgtatct
           ataaaagatc tcttaaccct aaaagatgaa catatggact ttgtcttatt cctcatacag
           GTGACTGAGC TTCCCTTCTT CGCATCGAAG GTGCGTCTGG GACGATGTGG GATCGATGAA
           GTGTACGGCC TTGGACCATT GAACGAATAT GAGAGgtaaa agttaaaatc ttgatcgatc
           tgacatcttg aatttacttc gacatgtttg tatgttcata tcgtttttcc gccctttctt
           tttgctaatt gatcagGATG GGATTAGAGA AGGCAAAGAA AGAGCTTTCA GTAAGTATTC
           ATAAAGGTGT TACCTTTGCG AAGAAATAAa gagactcgat cgtgaataaa cacacttaag
           cgatggtttt ggaatagtca gagttttgga ataagaataa tgcctcacaa taaaagctct
           tgcggtcttc ttggatccaa tcttaaaggt tcaagaaact catctccttt aggtaaaatc
           ttcgattgtt ttatcgttcc atcgaaccac tttgttctta gatacaagaa cgtttatgat
           ttatgtagtt gggctataaa agtgagaaca gagcaataat cttgcaacat tttttctcat
           cttcttggtg tgtttttttt ttgttggttt tcatcttttt gttcttgctc atgagagcat
           ctttagaagg ctattgttgg gaagtaaata agtttgcatc gcggaaaaga tgatcaaggt
           cattcgggat acctcatacc tgtcatttga gttcatctaa gtaacttctt acgcttttag
           gctatctacg gttgttctta ggatttaggt gttagtggtt atgctatta
12         aacaaaaata ctcgaattca aacttaagca gtcacagtaa cttcgtgcag gagcttaccg
           gagatgaatt catcataaac cggcgacggt agcggcggag caaagcaaaa atgcgatgat
           tcatggaata ggtctcaaaa gtcacgagag gatcacgtga gatatcttga aaagaatcgg
           acggctaaga ataaagcaga ctaattctct tatctatctc taaccgttaa ataaaaacta
           aagttttaac cttttaacct gggactaggg ttttcagatt tcactactct tgtcgtgtaa
           gacttgagca actatataat ctcaactttt ctcaatcact atccgctgcg gtctcgccgt
           gctgcccaca acaatctccg acttcgtctt cctcatctat catcgtcgtc gtcaacctta
           tttatctctt aatttatcat taaaaccaaa aaaccaaaaa aaaagcctta gctttcgttt
           cttcaatccc agcaaaaaaa ATGGCTCAGG TTCAAGCTCC TTCTTCACAT TCTCCTCCTC
           CTCCTGCTGT TGTTAACGAC GGGGCTGCGA CGGCTTCTGC TACCCCTGGA ATCGGCGTCG
           GCGGCGGTGG AGACGGAGTC ACTCACGGTG CTCTTTGTTC TCTCTATGTC GGAGATCTGG
           ATTTCAATGT CACCGATTCT CAGCTTTATG ACTATTTCAC CGAGGTGTGT CAGGTTGTAT
           CTGTTCGTGT TTGTCGTGAT GCTGCTACCA ATACTTCTCT TGGTTATGGT TATGTCAACT
           ACAGCAACAC CGACGATGgt ttgtgcccta aaaatttccc cttttttttg ttgattgata
           acatttgata ttttggtaaa gatctgattt ttcggttttg gaatcattcc tttggctagt
           ttgattgatg ggttttgttt gattttgtta atagatatta atttacacga atttaaaatg
           ttgacactga ttagggattt tgttatcatt gttgtttttt gtaatgtcag CGGAGAAGGC
           AATGCAGAAG TTGAACTACA GTTATCTCAA TGGGAAGATG ATTCGGATTA CTTACTCTTC
           TCGTGACTCT TCTGCCCGTA CAAGTGGGGT TGGGAATTTG TTTGTAAAGg tatattcttt
           gtttgatgtc tcttatctag cagcttctct ttttgtttga ttgcctaatt atgtattctt
           tctttatgtg aagAATTTGG ATAAGTCAGT TGACAACAAA ACTCTGCACG AGGCGTTTTC
           CGGGTGTGGG ACTATTGTGT CCTGTAAGGT TGCTACTGAT CACATGGGTC AGTCTAGAGG
           ATATGGGTTT GTGCACTTTG ACACTGAGGA TTCAGCTAAG AATGCTATTG AGAAGCTGAA
           TGGGAAAGTG TTGAATGACA AACAGATTTT TGTTGGACCT TTTCTTCGTA AGGAGGAAAG
           AGAGTCTGCT GCTGATAAGA TGAAGTTTAC TAATGTTTAT GTGAAGAATC TTTCGGAGGC
           GACTACTGAC GATGAGTTGA AGACTACTTT TGGTCAGTAT GGTAGTATCT CGAGCGCTGT
           AGTTATGAGG GATGGAGATG GGAAATCCAG GTGTTTTGGA TTTGTCAACT TTGAGAATCC
           TGAAGATGCA GCTCGTGCTG TTGAAGCTCT CAATGGAAAG AAGTTTGATG ATAAGGAGTG
           GTATGTGGGT AAAGCTCAGA AGAAATCTGA GAGGGAACTT GAGTTGAGCC GGAGATATGA
           ACAAGGCTCA AGTGATGGTG GAAACAAATT TGATGGGTTG AATTTATATG TTAAGAACCT
           TGATGATACC GTCACCGATG AGAAGTTGCG CGAGTTGTTT GCCGAATTTG GTACAATCAC
           CTCTTGCAAG gtcagcattg tttgttttcc gcatacataa taacatgaga gatgcaattt
           tttttgtctc ttgattgatc ggaacctcat acttttgtaa caaacagGTT ATGCGGGACC
           CTAGTGGTAC TAGCAAAGGA TCAGGATTTG TTGCCTTCTC TGCTGCCAGT GAAGCTTCAA
           GAGTGgtaat ttaaataatc ctgtgtcaag acaatattaa atttgttttg agcctctatt
           ttctttcttg attcaatttc ttttggggtc ttctgcagCT GAATGAAATG AATGGTAAAA
           TGGTTGGTGG CAAACCGTTG TATGTTGCTC TTGCACAGAG GAAAGAAGAA AGGAGGGCTA
           AGCTGCAGgt agtacttccc accatagata aacaacccct acgtacactt atgtttgcta
           tgtctcaagt ccttatgttt ctttttcagG CACAGTTTTC TCAAATGAGA CCTGCTTTTA
           TCCCCGGTGT CGGTCCTCGA ATGCCAATAT TTACAGGTGG TGCTCCAGGT CTTGGACAAC
           AGATTTTTTA CGGTCAAGGA CCTCCACCAA TCATCCCTCA CCAGgtacca ttttgttcta
           actgaccact atgtaactct gcttgaatat gggactcttt caatcaataa gcactcactt
           ggttctactt aaatctgtga tatagCCTGG ATTTGGATAT CAGCCTCAGC TGGTTCCTGG
           AATGAGGCCG GCCTTTTTTG GTGGACCGAT GATGCAGCCA GGTCAGCAAG GTCCACGACC
           AGGTGGCAGA CGGTCAGGTG ATGGACCCAT GCGCCATCAG CATCAGCAGC CAATGCCTTA
           CATGCAGCCA CAGgttagtt tataaaaaaa ggagaatatg tcttaaatcc cagatcaaga
           tgaatctata agtctttgct ttcttctctc ctctagATGA TGCCAAGAGG ACGAGGGTAC
           CGGTACCCTT CTGGTGGTAG AAACATGCCT GACGGTCCAA TGCCAGGAGG AATGGTTCCA
           GTTGCTTATC ACATGAATGT AATGCCGTAT AGTCAGCCTA TGTCCGCTGG TCAATTGGCT
           ACTTCCCTTG CTAATGCTAC ACCTGCTCAA CAGAGAACAg taagtctctc tcaatacctc
           ttgacttgct gctatgtagg agaaaaaata agattactta cattcgatat gtttgttttg
           gggtttttgt agCTTCTTGG TGAGAGTCTA TATCCATTAG TGGACCAGAT AGAGAGTGAG
           CACGCTGCGA AAGTGACTGG TATGCTTCTG GAAATGGATC AGACCGAGGT TTTGCATCTG
           CTCGAGTCAC CAGAGGCTCT AAATGCCAAA GTTTCAGAGG CATTAGATGT GTTGAGAAAC
           GTGAATCAGC CATCTTCACA GGGAAGTGAA GGCAACAAAA GTGGAAGTCC AAGTGATCTC
           TTGGCTTCAC TTTCCATCAA TGATCATTTA TGAgaagctt ttgttcgagt tttttttttt
           actttgactc tcttcctctc tatctctctc tctgattgac aaatttttgc gggaatctat
           ttgctgtttt agactttttt tgctcgatat gattgtttct gttttgactt cttacttttt
           tgggttgact taaaaaagga tggttttatt ttattttgtt ggattatatt ttactgttgc
           aaaattttgc gctcagttta aaacttttta tgattgattt aagtttttag ttatttgttg
           gtaattgtca attttgaacg agaaggtgat gaaattagga tatgtatagt tcattagcta
           attaatccaa ttttagtttt tcacaaatat taacaactga ttataaatgt atcatttttt
           gtgattacca attttcataa ttctaaacca atagtaaatt actttgtagt aaaatcaaca
           caaactcatg gaccatgact cgtaaagaag ataaaaacaa gtggtacatt tat
13         atatcaacat caaacaatat tatagcaaag ataatgtgat tatttggtta ttgtaattga
           aattaatcca tataccaatt cattttgttt tgttatatat atcgagaggt tattgtgatt
           taaaaaaaaa aaatatttaa tcatctaccc agtaaaacta cgccacataa ccaccacaat
           aactctaaga gcacttctta ccttgaaacg tctcttactt aaattaataa ttaaatcttt
           aatttttatc atttattaac ctaagaaaca gctaataaat atttattaat ctaagagact
           tacacgtctc tctttcttat aacatatcaa catcaaacaa tattatagca aagataatgt
           gattatttag ttattgaaat tgaaattatc cacacaccaa ttcattttgt tttgttatat
           atatcgagag gcctaagaca acacttacac gtctatcttt ctttcctttg tataccaaaa
           aatataaaat aaaaaacact ATGGCGGAAA ACTACGACCG TGCCAGTGAG TTAAAAGCAT
           TCGACGAGAT GAAGATTGGC GTGAAAGGAC TCGTCGACGC CGGAGTCACA AAAGTCCCGC
           GCATTTTCCA TAACCCGCAT GTTAACGTAG CAAACCCTAA GCCTACATCG ACGGTGGTGA
           TGATTCCAAC AATCGATCTA GGTGGCGTGT TCGAATCCAC GGTCGTGCGA GAGAGTGTAG
           TTGCGAAGGT TAAAGACGCA ATGGAGAAGT TTGGATTTTT CCAGGCGATT AACCATGGGG
           TTCCACTTGA TGTGATGGAG AAGATGATAA ATGGTATTCG TCGGTTTCAC GACCAAGATC
           CAGAAGTGAG GAAAATGTTC TATACCCGAG ACAAAACCAA AAAGCTTAAA TATCACTCTA
           ATGCTGATCT CTATGAGTCT CCTGCTGCGA GTTGGAGAGA TACCTTAAGT TGTGTCATGG
           CTCCTGATGT TCCAAAAGCA CAGGACTTAC CTGAGGTTTG TGGgtaagaa tacatttctt
           taatttattt ctaatctaag aagaaacaag actagtttaa actttgattt gatattattg
           atgtggtttg aaaattggtt ggtgtgaata ttgttagGGA GATCATGTTG GAGTACTCAA
           AGGAAGTGAT GAAGTTAGCG GAGTTAATGT TTGAAATTTT ATCAGAAGCT TTAGGGTTGA
           GTCCTAACCA CCTCAAAGAA ATGGATTGCG CAAAAGGTTT ATGGATGCTC TGTCATTGTT
           TTCCACCCTG TCCTGAGCCA AACCGAACAT TCGGCGGCGC TCAGCACACA GACAGATCTT
           TCCTTACTAT TCTTCTTAAC GACAACAATG GAGGACTTCA AGTTCTCTAC GATGGATACT
           GGATCGATGT TCCTCCTAAT CCCGAAGCAC TTATCTTTAA CGTAGGAGAT TTCCTCCAGg
           caagtcgttg tttactcttg aattgaatgg tctataaaaa cccataagtc acaaaaagta
           agtctttttt tttttttttg cagCTTATCT CGAATGACAA GTTTGTAAGC ATGGAGCATA
           GAATTTTGGC AAATGGAGGT GAAGAGCCGC GCATTTCGGT CGCTTGTTTC TTTGTGCATA
           CTTTTACTTC ACCAAGTTCG AGAGTATATG GACCCATTAA AGAGCTTCTG TCTGAGCTAA
           ACCCTCCAAA ATACAGAGAC ACCACCTCGG AATCCTCCAA TCACTATGTG GCTAGAAAAC
           CTAATGGGAA TTCTTCGTTG GACCATTTAA GGATCTGAaa cttgaaccta tatctcagag
           gttttcttga gtttccaata aaatttggtg cacgctgtga cgtaccatgt tcaagacctt
           gaacgtatca ttcaataatt cttccgttgt gagtttcggc tgcatgtttg acccaaacca
           gagagagtat ggatcaatca aggagagtga acctaaaaat aaaaaaaaaa taaaaaaaag
           agtgtgaacc tttaattatg taaaatctta aataaacatc gagattgtat ttaaggattt
           tccatttgtt ataatctcaa tttaccttta atatgaggtt tatattcttt cttataacat
           atcaacatca aacaatatta tagcaaagat aatgtgatta tttagttatt gaaattgaaa
           ttatccacac accaattcat tttgttttgt tatatatatc gagaggccta agacaacact
           ttggcgtcta tctttctttc ctttgtatac caaatgtttg attttgttat ttaaatca
14         acgtacgatg cctgagctgc gtagcaacgc acgcagagat cgggataaga agaacccgaa
           gcagaaccca attgctttga aacaatcacc tgttaggaga aatccgaggc ggcagctgaa
           gaagaaagtg gtggtgaagg aagcgatcgt tgcagctgaa aagacgacgc ctttggtgaa
           agaggaagaa gaacagatta gggtttcgag tgaagataag aagatggatg agaacgacag
           tggtggtcaa gcagctccag tgcctgatga tgaaggaaac gctcctccac ttcctgaaaa
           ggtgtcaact ttattgttgg ttttgttgtt tttatgaggt tttagttcat cggaattgtc
           tcttgcattg tgtgttgtgt tttttgatta ggagaaagct ctcaaactta ggcatgccac
           ttaaagttaa aactttctct tgtaggatga tttgattatt gactccttgg tttttacagg
           ttcaggttgg taattcaccc ATGTACAAGT TAGATAGAAA GCTAGGCAAA GGTGGTTTTG
           GACAAGTTTA TGTTGGTCGA AAGATGGGCA CGAGTACTTC TAATGCTAGA TTTGGCCCGG
           GAGCTTTGGA Ggtatgctgt ttgtgtttgc aagtttactt gctttctttt ggttttctgt
           gatctgtaat gtgattttga tgtgtccact tttgtagGTG GCTTTGAAGT TTGAGCATAG
           AACCAGCAAA GGATGTAACT ATGGGCCACC GTATGAGTGG CAAGTTTACA Agtgagcgtt
           atggtctctt gtctttggct ctaggattca tcttctgctt gttcaaatag tttgtttata
           aaaggatgag ataactaatg atgctttatc atctgttcgt ccagTGCACT TGGTGGCAGT
           CATGGTGTGC CACGAGTTCA TTTTAAGGGT CGGCAGGGCG ATTTTTACGT GATGgtatgt
           ggaatttagt caggtctgaa caagagcact tgcagtatga tgaattactg tttttaatct
           ttcatacagG TTATGGATAT CCTTGGGCCT AGCTTATGGG ATGTTTGGAA TAGTACCACC
           CAGGCgtaaa cattcactct gagaaacatt tactttattt tgtagcatct gaagattttg
           ttatatgaac cattgataaa cataattttt cctgagatga gcccttcaat attggtggca
           ctcaccatat gatttgtgtg ttttatacat tccagGATGT CAACAGAGAT GGTTGCATGC
           ATTGCAATTG AGGCAATATC CATATTAGAA AAGATGCATT CTAGAGGgta attttctaat
           atttctgcta ctgtaactct ctttcttcaa gtggttttta tttgctaaga agcagtgctc
           ctgtttctac agATATGTGC ATGGCGATGT AAAACCAGAG AATTTTCTGC TTGGGCCTCC
           TGGAACTCCT GAAGAGAAAA AACTTTTCCT TGTAGACCTC GGCTTAGgta cactttattt
           ttgttataag agtgagcgta ctttattgtc tttctgctgc ttatccaatc tgttgatctt
           gcagCATCCA AATGGCGAGA TACTGCAACT GGACTACATG TTGAATATGA CCAGCGTCCT
           GATGTTTTTA Ggtaagttga ttcagctagg cataaagcct gtgagattga ttcttatcag
           ggacttcaac tttagggtac ttattaacgt gttggctttt tcattttcag AGGAACAGTA
           CGTTATGCTA GTGTACATGC TCATCTTGGC AGAACTTGCA GTCGGAGGGA TGACCTGGAA
           TCTCTTGCTT ACACTCTTGT TTTCCTTCTT CGAGGCCGGC TTCCATGGCA AGGGTACCAG
           GTTGGGGACA CTAAAgttat ttgttttatt tcctggcaac tttccttgtc aatcattaac
           ttggtctatt tgttagggag agAACAAAGG TTTCCTTGTT TGCAAGAAGA AGATGGCCAC
           TTCCCCAGAA ACTCTTTGCT GCTTCTGTCC CCAACCTTTT CGTCAGTTTG TCGAGTATGT
           GGTCAATTTG AAGTTTGATG AGGAGCCTGA TTATGCTAAA TATGTCTCCC TTTTTGATGG
           AATAGTCGGC CCAAACCCAG ACATTAGGCC AATAAATACT GAGGGTGCAC AGAAGGTGAT
           TTGGTGAtct tctttatgaa acatatattg aggtttacta tttagctccg gtctgaatgt
           ctaaagtttt ttcgtgtttg tctggtgtga agctcataca tcaagtgggt caaaagaggg
           ggaggctgac aatggacgag gaggatgaac aaccaacaaa gaagatcaga ttgggcatgc
           cagcaacaca atggatcagc atttacagtg ctcacagacc aatgaaacaa cggtgacatc
           ttggatcata cttgagaatt cttcggctgt acgttgatga ccatgcagct gacatgtctt
           ttatctttgt gcagatatca ttataatgtt actgatacaa ggcttgcaca acacattgaa
           aaaggaaatg aggatgggtt atttatcagc agtgtggctt cttgcacgga tctctgggct
           ttgatcatgg atgcaggaag tggctttacg gatcaagttt accagttatc accaagcttt
           ctccacaagg tagcttcatt taatatt
15         tgtctaactg catgtctatc atgtacatta agatcaagac taatataaaa ctcacaaatc
           aatatactac ttaagaaaaa gaaaaaaatc tggttctttt ttattcatgc acacacatag
           tataagttaa aaaatgacca tattaatttg taaactgacc aatcgtgtat ataaaaggac
           accttctcta cctacttata tattatacat catttctcta cattgttcac cagctctctc
           catctctcta ctccaagcat aagaggtaat ctctcaatag tttgaaacaa ccttttgtaa
           aacgtattgt aacttactta aaattgtaga acgtgagaaa tatcttaaat gtttaaagtc
           ttcctttttc acccaagaac tgaaaatgat tttgcatata tattttctca agtgggtata
           atggatataa agaaattata caatgactaa ggaacaaaat aaaatctctt ttattgaata
           atgatttgaa tcagttctcg ATGGCCCAAA GGTTGGAGGC AAAAGGCGGA AAGGGAGGGA
           ATCAATGGGA TGATGGAGCC GACCATGAAA ATGTAACAAA GATACATGTA CGAGGTGGTC
           TTGAAGGAAT CCAATTCATC AAGTTTGAGT ATGTCAAAGC TGGACAAACA GTTGTTGGAC
           CAATTCATGG TGTCTCGGGT AAAGGTTTCA CACAAACGgt aagcatgtta aatatagaac
           tacctgaact cttttttttt gaagatataa ggttgtatcc tggattgaat gtttagaaaa
           tttgaacaca gaaactaatc ggttgtgaag gtgatatgat gttaatagct agatgtacat
           gtatatcctt actatatata tcagaacttt ttagttggtc aacttttaat gatcggtgct
           taaattttat taattaatcg agtctccata attgttttaa attatccccc acagcttata
           tattactgat caagttttaa tattcttttt tttttcttac agTTTGAGAT TAATCATCTC
           AATGGCGAAC ATGTGGTGTC AGTAAAAGGT TGCTATGATA ACATATCCGG TGTGATCCAA
           GCACTTCAAT TCGAAACCAA TCAAAGGAGT TCTGAAGTCA TGGGATACGA TGACACTGGC
           ACTAAGTTTA CACTTGAAAT CAGTGGAAAC AAAATCACTG GGTTCCATGG ATCTGCTGAC
           GCAAACCTAA AATCTCTTGG AGCTTATTTC ACACCACCTC CTCCTATTAA ACAGGAATAC
           CAAGGTGGTA CTGGAGGCAG CCCATGGGAC CATGGTATTT ACACCGGCAT AAGAAAAGTC
           TATGTTACAT TTAGTCCCGT TAGCATATCG CATATCAAGG TCGACTACGA CAAAGATGGA
           AAAGTGGAAA CGCGTCAAGA CGGGGACATG CTTGGAGAAA ATAGGGTCCA AGGACAACCA
           AACGAGgttc tagttttaac actccttact tcttattatt ttagtttttt ttggtaaaat
           gctaaatctt taatagaaag gaatatgtca agagtaaatc atatatggga agaatcataa
           accattcgtt aacccttcaa ttttttaaaa tatataaatt gaaggatccc tttatttgtt
           ttttgcagTT TGTAGTGGAC TATCCATATG AATATATTAC ATCAATAGAA GTGACCTGTG
           ACAAAGTCTC TGGCAATACA AACCGAGTTA GGTCGTTGAG TTTCAAGACA TCAAAAGACA
           GAACATCTCC TACATATGGA CGTAAGAGCG AGCGAACTTT CGTGTTTGAG AGCAAAGGTA
           GGGCTCTTGT TGGGCTCCAT GGAAGGTGTT GTTGGCCTAT TGATGCTCTA GGTGCACATT
           TTGGTGCGCC TCCTATTCCT CCACCTCCTC CCACGGAGAA ACTACAAGGA TCAGGTGGTG
           ACGGAGGAAA ATCATGGGAC GATGGAGCTT TCGACGGTGT GAGAAAGATA TACGTGGGAC
           AAGGTGAGAA TGGTATCGCA TCTGTCAAGT TTGTGTATGA CAAGAACAAC CAGTTGGTAC
           TAGGAGAAGA GCATGGAAAG CATACTTTGC TTGGATACGA AGAGgtgatt aattatacta
           tacttcgttg ctattttctt aaactataac tataaagttg tgttattgtt attctgatga
           accgctttca cagTTCGAGT TGGACTATCC GAGTGAATAC ATCACAGCGG TAGAGGGTTA
           TTATGATAAA GTGTTTGGTA GTGAATCTTC AGTAATAGTC ATGCTTAAGT TCAAGACCAA
           TAAACGAACC TCCCCGCCTT ATGGAATGGA TGCTGGCGTT AGCTTCATAC TCGGGAAGGA
           AGGTCACAAA GTGGTAGGGT TCCATGGAAA AGCTAGTCCC GAGCTCTATC AGATTGGGGT
           CACTGTTGCC CCAATCACCA AGTGAcgacg tccttgaact ttattctcaa atcaagtttg
           atcatgcata tttgttaagg cgcctctctc gtattgtctc caccactttt ctacgtgttt
           tgttttctcc gatgttttac tttgaaaaat ctatttcaat caagcaatat cgtgtaataa
           aagcaaggtt ctcgaacctg cgggtaaact ttttattttg aataatttat tttcaatcaa
           gcattctttt gactttttgc tttaaccaaa tgtctctagt ttcaaaaaag attaagaact
           caaagatata agaattactt tcttattaag cttactttct tattaagctt aggaaaatta
           ctcaaaacgt aaacaatctc aaagtcttaa tttctctaaa ctcatatagt caaccacagc
           ttgggactca tatatataga gattaataaa ccaaaacata ctaggattag cattagataa
           ctcctaacat atatctttag atatctccta aagatttaac ataat
16         ttctaaggaa atgttttgtt aatatgaatt cattaactgc aacctaaaga aaagtttgtg
           aataactcag cgtgacctaa tcctacaaaa aaagtataat gttccactca gagtcactgg
           tcaaaaagta ttaattcttt aaaagaacct ctttttgtgt tgtataatga actagtttgg
           ttataaactt ataacttaaa gggacatggt tgttgactta aacttaggta gaattgtttt
           ttatatagaa atggagcaag tcgatcttaa atgttagatc ataaataaac ttctcatgaa
           acctaaaaga aaaaatatat aaacacccaa acccattcca ttcacttcaa caactcaatt
           acaattatgc ttatatatct tacatgcaaa acttcatcat tatcatcatc atctctagct
           cctcctttga atcttttcca aattcaactt ccgaaagaga taaccctaat ttctagtctt
           cttcttctaa attttcttcc ATGGATATCG AAAAGGCAGG GAGCAGAAGA GAAGAAGAAG
           AACCCATTGT TCAAAGGCCA AAGCTAGACA AAGGCAAAGG AAAGGCTCAT GTATTTGCTC
           CTCCTATGAA CTACAACCGG ATCATGGACA AACACAAGCA AGAAAAGATG AGCCCTGCCG
           GGTGGAAAAG AGGTGTAGCA ATCTTCGATT TTGTTCTTAG ACTCATCGCA GCAATCACAG
           CTATGGCTGC TGCAGCAAAG ATGGCGACAA CGGAAGAGAC TCTTCCTTTC TTCACTCAGT
           TCTTGCAGTT CCAAGCTGAC TACACTGATC TACCAACTAT GTCgtaagtt tctctccaaa
           tgttactctt actataggtt atgccaagaa tgtagtaacc aactatggaa atgaaacccc
           aaatgtgtat agtcgtacta tagataatac caagactgct acgtagctta acccgttgaa
           tccaaccaaa gccaggctag ttgcaaagtt caagcagtag ttagagagaa aaaatgagct
           acgttttaaa taagggggga aaaaaaacta tcaacatgaa tttcgagcaa tgtgcttggt
           gcttattagg gatttaatta tggtacatga ttttcaatta tataaagatt caaacttata
           tcattttttt ttattgtttt gttttgcagA TCTTTTGTGA TAGTAAACTC AATCGTGGGT
           GGCTACCTAA CCCTCTCATT GCCTTTTTCT ATAGTCTGTA TCCTCCGCCC CCTCGCGGTG
           CCGCCTAGGC TATTCCTGAT CTTATGTGAT ACGgtaacat ttataaaaaa aatttgaaaa
           taaatagtta taataatgca atgccaaaca tacaaatgaa atttctcatt ttgtttgtgg
           tttaacaatg aaacttttcg tagctttaaa aaaaagtaca aacgcaaacg ctaaaataag
           tcaaggcttt acttaagctc gagtaatcct tatattggtc acaaattaca atgaatatgt
           ttgttgagta aacatatgac aaatccctct aactagttcg tacggttgtg ttggtccagG
           TGATGATGGG CCTCACCCTC ATCCCCCCAT CCCCTTCCCC ACCCATACTT TACTTGGCGC
           ACAACGGGAA TTCAAGCTCG AACTGGCTTC CGGTTTGCCA GCAGTTTGGT GACTTTTGCC
           AAGGAACGAG CGGTGCCGTG GTGGCATCCT TTATTGCTGC GACTCTTGTC ATGTTCCTCG
           TCATCCTATC TGCATTTGCT CTCAAGAGAA CAACCTGAaa acttggattg atcctcttga
           ttaaattttt atgtgctttg atattcattt gtgtgaattt ttattaaaag gttcctatgt
           ataatttggt tttgttgtgt ttggtaactc gggttttagt gtggaaaaat gttgtaaatc
           aatcttctat attcacatat tgttttcttt ttccctatat aattttcgtt tcaaagataa
           caaattttaa acttatatct gcccggccat aattttaatt aaattagtaa gggtgttaag
           ttgatgtaat atcacatgat tttaaatatc taagtaacta actaattata
           tatcattata tttatatatt tgactaggtg gggctcaatt ggctccaaag aattttgttt
           gcatgcttaa ttattttgta tttggtggat gatttgattt gaaatgataa aagtttaatc
           cattgtcctt ccacctcttc tagcatttga tattttctcc tattaattgt ttaatatg
17         ttgtaataag taaattcggc cacctagttc tccggtgaaa gaaagaagaa gacacaaatg
           gagctccgtg acgtggaaaa acattattag gcccaaaacc ctctgactta aaaaagactt
           gataattgaa taaatagttt aatgtcgttg acataaacgt aagccgtctt agctcagtgg
           tagagcgcgt ggcttttaac cacgtggccg tgggttcgat ccccacagac ggcgttttcg
           tattccgaca taggttgtct tttttgctgc ttttctttaa ctgaaatatt ccgaccaatt
           ttttccagct gataagccca acggacaatg tgtaatattg cgattttata taaaagtttt
           gggccttttg attttccttg caataattaa cactcggtct tctccaacct aacaattatt
           ctagggtttt agagtttccg cacgaatcac gaatctctct ctctttcaca cacttcacac
           tttcaatata cactctcatt ATGACTACCG AAGAGAAAGA GATCCTCGCC GCCAAATTGG
           AAGAACAGAA GATCGATgta attgattact cttttattct ttacctatct atcatctctg
           tttatttgtt gttatttgtc ttttagtctg gaaatcatta gactgaattc agagtttttt
           aatctgttcc tgcccagatc tttgcttttg ttttgttttg tatatgcaaa tattggacct
           tattataaga ctttagatct gaatttacat gtaattaacc tttgtggatt ctctcatttt
           cccaattagt tcaattattg atgatttgtt gtagCTCGAT AAGCCCGAAG TTGAGGACGA
           TGATGATAAC GAAGACGATG ACTCTGATGA CGATGATAAG GATGATGACG AGGCTGATGg
           taaaagcttt ctacatttca ttcatcaaat tactggaata attagtatag ttcctagtat
           ttctgttagc ttacatctgg ggcagatttg ttgatgctca cgtgtatgtg tagatatgta
           gcaatgataa ttatatggcc atagcttgaa aatttagtga aaatgaatcc atcttctttg
           ttttcaaata atctttgcgt tgacttgtgt tgatagacat gtttgtggaa cttaatgtta
           tcatctattt tattcttgtt gattggtgat tggaaaacag GACTAGATGG AGAGGCAGGA
           GGTAAGTCAA AACAAAGCAG AAGTGAGAAG AAGAGTCGCA AAGCCATGCT CAAGCTTGGC
           ATGAAACCCA TCACTGGTGT TAGCCGAGTC ACCGTCAAAA AGAGCAAGAA Tgtttgtgtt
           ttctctttaa tattcagtca atcttaattt cttttattca cacatcaggc tttaatattg
           atctgttttg gggacatttg ctttggaaca cagATCTTGT TTGTCATATC AAAGCCTGAT
           GTGTTCAAGA GTCCAGCATC AGACACATAT GTGATCTTTG GAGAGGCGAA GATCGAGGAT
           TTGAGCTCTC AGATCCAGTC GCAAGCAGCA GAGCAATTCA AGGCACCAGA TCTCAGCAAT
           GTGATCTCAA AGGGTGAGTC ATCGAGCGCT GCAGTGGTTC AGGATGATGA GGAGGTTGAC
           GAGGAAGGTG TTGAGCCAAA GGACATTGAG TTGGTGATGA CTCAAGCAGG AGTGTCTAGG
           CCAAATGCTG TGAAGGCTCT CAAGGCTGCA GATGGAGATA TTGTCTCTGC CATCATGGAG
           CTTACCACCT AAaccaaagt cttttctact tagatgtggt ttaacctgag ttatgtgcca
           gagattgtcc aaagaattcg gaaatttttg gtttcaatgt ttttcatgaa gtgattttcg
           atgttgtatc agtataaacc tcataagttt ttgattttca gtttgatttt atattgaata
           tcaagtccaa gtgtttacca ttatagactt gtagttataa tttgtcaagt atcagtctgt
           ttaatgaacc gaacccaaag gatatggaca ccccttcact ccaaccaata cgaggtatca
           actgaggtta atcgatacat gcagtacaat gtacaaagtg ctacaagtgg aggttcatag
           actagaaaag tattcaacag gacctgattc taagagaaat tgttataaag ccgatgttta
           ttacctaact cctcaaggaa ggaggctagg gagttgcaag gaaggagctg gttttatcca
           agactacgaa agattcaaag gcacactgat ga
18         tcgatctgtg ttttgatttc tcgatcttga atctgttgga tcttgaatcc agtgagctga
           ttttgagtct tgttcagata tatttgatat tgcctagatt cagtttcggg tttctcaata
           tatttctcga ttgttaggtt tctatattga ttcaaatcga ttcatttgtg gcgagtttga
           ttgatttgag aatgtttgct ttccactatt ctaatggtta attgtgtaat tctttgcttc
           cttgactcac cttgtttgta gaagctacag atctgttgca gaaactatcc ttggactcgc
           cagcaaaagc ttcagagatc cctgagccta acaagaaggt gatttgcaga ttgaattttg
           gttttctgtt gtcacaacct ttgcttcttc cagttttttt taacgctttt gttttgtgtc
           ttgtgtagac tgccgtctac cagtatggag gcgttgatgt tcatggtcaa gttccttctt
           atgatcgatc tttgacacca ATGCTTCCCA GTGATGCTGC TGACCCTTCA GTTTGCTATG
           TTCCTAATCC TTACAATCCC TACCAGTATT ACAATGgtag cttcatcctc aaatcattta
           caatctagaa acattatttc actaaattgt caccactggt ttaacaagtt tttcgttttg
           taacttttca gTATATGGGA GTGGTCAAGA GTGGACTGAC TACCCAGCTT ACACAAATCC
           TGAGGGTGTT GACATGAATT CTgtaagtgt gtgctgacta gttataatag tgcctttcat
           cgtctttata ttttctttgc ttaacaggtt caatatttta ccagGGAATT TATGGAGAGA
           ATGGGACTGT TGTGTATCCT CAGGGTTATG GGTATGCAGC GTATCCTTAC TCGCCAGCAA
           CTAGCCCTGC TCCACAGCTT GGCGGGGAAG GGCAGTTGTA CGGTGCTCAG CAGTATCAGT
           ATCCTAACTA TTTTCCAAAC AGTGGACCGT ATGCTTCATC TGTGGCTACA CCTACCCAGC
           CGGATCTCTC TGCAAACAAA CCTGCTGGTG TGAAGACACT ACCTGCGGAT AGCAATAATG
           TTGCTTCTGC TGCTGGTATC ACAAAAGGAA GTAATGGATC AGCTCCAGTG AAACCAACTA
           ACCAGGCTAC CCTTAACACC TCAAGTAATT TGTATGGTAT GGGTGCTCCA GGAGGAGGTT
           TGGCTGCTGG TTATCAGGAC CCCAGGTATG CCTATGAAGG GTATTATGCT CCTGTGCCGT
           GGCACGATGG CTCTAAGTAC TCTGATGTGC AGAGACCTGT TTCTGGTAGT GGAGTTGCAT
           CCTCCTATTC TAAGTCTAGC ACAGTACCTT CATCGAGGAA TCAAAACTAC CGCTCAAATT
           CTCACTACAC Ggtatgatgt ctttccaaac ttctttttgc taatgaacac cattgtctgc
           tttactggca tatatatata gccgctcaag tcttccaaat ttgttaactg accttcaatc
           aacttttttc tttgcagAGC GTGCACCAGC CTTCATCAGT GACTGGCTAT GGTACAGCTC
           AGGGGTACTA CAACAGGATG TATCAGAACA AGTTATATGG TCAGTATGGT AGCACAGGGA
           GATCTGCTTT GGGTTATGCT TCATCTGGGT ATGATTCAAC AACAAATGGA AGAGGATGGG
           CGGCCACAGA CAACAAATAC AGAAGCTGGG GCAGGGGTAA CAGTTACTAT TACGGAAATG
           AGAACAATGT AGATGGTTTG AATGAACTTA ACAGGGGACC TAGAGCTAAG GGCACAAAGA
           ACCAGAAGGG AAATCTAGAT GATAGCTTAG AGGTTAAGGA GCAGACTGGA GAATCAAATG
           TAACTGAGGT TGGGGAGGCG GATAACACAT GTGTTGTTCC TGACAGAGAA CAGTACAATA
           AAGAAGATTT CCCAGTGGAT TATGCAAATG CCATGTTCTT TATCATCAAG TCATACAGTG
           AAGATGATGT GCACAAGAGC ATTAAATATA ATGTTTGGGC TAGCACACCA AATGGAAACA
           AGAAGCTTGC TGCAGCATAC CAGGAAGCTC AACAGAAAGC TGGCGGCTGT CCCATCTTTC
           TGTTTTTCTC Ggtgtgtata taatcctgaa attaaaaact gtgctctttt tactttgttt
           tatgatattg ttctttatac tccagttttt gtctttcagG TCAATGCAAG TGGACAATTT
           GTTGGTCTTG CTGAAATGAC AGGACCAGTT GATTTCAACA CAAATGTGGA GTACTGGCAG
           CAAGATAAGT GGACCGGCTC TTTCCCCCTC AAGTGGCATA TTGTGAAGGA TGTGCCAAAC
           AGTTTACTGA AGCATATTAC TTTAGAGAAC AATGAGAACA AACCTGTTAC CAACAGCAGA
           GACACACAAG AGgtaaatat ttgtgacatc ttttggcttg ttttactgat tactccacga
           gcgtttttgt tttcttgtgc ctaactttct ttgtttggat catattagGT TAAGTTGGAG
           CAAGGTTTGA AGATTGTGAA AATTTTCAAG GAGCATAGCA GCAAGACTTG CATTTTGGAT
           GATTTCTCAT TCTACGAGGT TCGACAGAAG ACTATCTTGG AGAAGAAAGC CAAGCAAACC
           CAGAAACAGg taagaactag aaaacaattt cagaaatctt tttcattcag tatatatata
           acttgagtgt ttctaatgta ttaaagctta acagGTAAGC GAGGAGAAGG TAACCGATGA
           AAAGAAGGAA TCTGCAACTG CAGAGTCAGC GAGCAAGGAA TCTCCTGCAG CTGTTCAAAC
           GTCCAGTGAT GTTAAGGTTG CTGAGAATGG GTCTGTTGCT AAACCAGTCA CAGGCGATGT
           GGTGGCAAAT GGTTGCTAAc taagaggatg gtgtcgctca cggcatgggc ataaaactga
           ctagagatga agatatgaac aatcccgttt aacgtttctc ttgagaagaa gattgccgtg
           agccttgaag catggaagga gctttagtac ctgagacgga tccgtttctt tgcccttaga
           agtttaaatc ccagttattt ttttttcaat cttttcttgt tttcattttt ccttttcttc
           aaaatcgcag tctcgttaca agtttatgtt gggtttcttt ttcattttct gttgttccta
           ccctgtaaaa atgcgcatag gacctactaa atcgtgggaa gaattagaga aaaggagata
           aaagcagggt gggattttgt tttttcatgt ctgttggatt tttaggcaga gttttctttt
           cttttggttt cttgctttgg tttcagactt gactctcttg agtcgtttag aatttgagat
           ggtcttttgc ctctctcgtc ttgtttctgt cattctcca
19         gagcgaggtc ttgtgtccag tttatgtttg aatcggtgat caaaacacaa tcctaaacag
           tgttagttaa tttaaaagct tcaatagcga aagacttact ttttgttttt ggtttctaca
           cttttataag tttactaatg cagaacttga tgaagctttt ttctgaattc attgattagt
           gaatatcatt atcttgttat tatcgtagac aaattgatat gagatcctta attatgatac
           caaataaaaa ccaccactaa agtgaaagaa aaaacaaagt caaagtaata tacaatatca
           tacaaatatc tgcaaaacgt ggaggaaaag aaaaatcgaa taattcgatg attctctcta
           tcaaagaaac gaaaaagtcg tattgaagtt ttgccatttg tttataaaag aagtggctgt
           tcaacgattc taaagtcatt tactttacca ttttgatctg ttgctctgtt tcactgtgcg
           tgatcgggaa gaagaagaaa ATGTTGGCGA TTTTCGACAA GAACGTGGCG AAAACACCCG
           AGGCTCTTCA GGGTCAAGAG GGTGGATCGG TTTGTGCTCT TAAAGATAGG TTCTTGCCGA
           ACCATTTCTC CTCTGTTTAT CCTGGTGCTG TCACCATCAA TCTCGGATCT TCTGGTTTCA
           TTGCTTGCTC TCTCGAGAAA CAGAACCCTC TTCTTCCCAG gttttgtaca atagtttatt
           cctcaggatg atgttttctt cttctgtcct agatatgaga gatttgctat cttaatgttt
           cactggcttg caaagatagt ttaggatatg tttcactgaa tctgagagat tgagatatcg
           atctgttgtt atgttttgat ggaataatga agttatatat ctactttgtt gtgatgttta
           aaatgtgttg aaactggaag gatgtgatta gataagtggt ggtgattttt tcaaaacaat
           tttgtgtgtg tgacagATTG TTTGCTGTGG TGGATGATAT GTTCTGCATA TTCCAAGGAC
           ATATAGAGAA CGTTCCAATT CTTAAGCAAC AATATGGACT AACCAAAACA GCTACAGAGG
           TTACCATTGT GATTGAAGCC TACAGAACTC TAAGAGATCG TGGTCCGTAT TCAGCTGAAC
           AAGTTGTTAG AGATTTTCAA GGCAAATTCG GGTTTATGCT CTATGACTGC TCCACACAAA
           ATGTCTTCCT TGCCGGGgta agtttgaatt ctgcttcttt actatttgac acttatttct
           gcatattgta atgctgaggt tattattatt atacgcgttt cagGATGTAG ATGGGAGTGT
           TCCTCTCTAC TGGGGAACCG ATGCTGAAGG ACATCTTGTT GTTTCTGATG ATGTTGAGAC
           TGTCAAGAAG GGTTGTGGTA AATCCTTTGC GCCATTCCCT AAAGgtatgt agcaagccgt
           ttttcgggtt ttgaagacat ctcactgttc tttgatctag tgcaaatatg aattaggatg
           tggttgtgtg tatgcataat gcagGATGTT TCTTTACCTC ATCTGGAGGT TTGAGGAGCT
           ATGAGCATCC ATCAAATGAG TTAAAGCCGG TACCAAGGGT AGACAGTTCG GGTGAGGTTT
           GCGGTGTAAC GTTTAAAGTG GATTCTGAGG CCAAGAAAGA AGCGATGCCT AGGGTTGGGA
           GTGTTCAGAA TTGGTCTAAA CAAATCTGAa ctagctgaaa aaggcttgtt ttatttttta
           cttgttggac tcctgtggct gtgttccaca gatttactct tttcctgata ttctcactgt
           agccattcta aggactaatg gtgctcttat tgctattgta cctgtacttg gtaacaagga
           agctaagaat aaaatatttt ataaacgtct aatgattcca gtgtatgcat atgatgtcat
           attgataaaa ccagagctgc aagaacatga gctccaacaa taacaattca taaacaacct
           ttggtaacaa aacaaaacct aaaactgtaa tgaaacataa tgacaggtct tagactctta
           gtaagagcct aaggttaaca ctgcctgcag atttctccac attctcttta cgcagaaacg
           cctcgggtaa gacttgagcc atccattttc agacctctgt tgtctgatgc tgctgctgca
           tagtcctgac tgttttccct tctccttgaa gtcatatcaa ggccaacac
20         ttgcttaaca ctcttaaatt attctcaagg aatctttcga ttgtgttctt aggattcaat
           tagtaataga cttgagtgtg tttgacatat ctattgggct tcgattgttt gttgcgttta
           catgttataa taggttttta tttcttggtt caaacgaaac caaaacttaa aagtaaatca
           tttttttcta ctgaattttg tttttgatgc ttttgatttc atttgatcac ttcaacttta
           gttccagggt cttgacgatt taattcaaaa agcaaaaaaa tcaataggaa acaaaaactc
           ataaaggact ttgacataca gatgggccca ttgtttatga ccaatcctta tactatatat
           gggccttatt agttaaacct aaggcccaaa gtcagattag ggttttcaga aagtgtacta
           taaattcttc ttctttaaac aacttcgtct agtggaacga cgacggcaca aaagcttcac
           cggagatcag agacgcgaaa ATGgtaaatt gtttcttctc tttcgatgtg attttggaat
           ttgtaaagtt cgttgacttt gaagaacaac aatacatggt tgattgattt attgtattgt
           ttttcagatc tatcataaaa gttttcaatc taaatgatgt ttgtattttg attaacctta
           aaagtctctt gattttgtat gtgtgtgagt gattcatttt tgattttatg aattttgaag
           GTGAACATTC CAAAGACAAA GAACACTTAC TGTAAGAACA AGGAATGCAA AAAGCATACT
           TTGCACAAGG TTACCCAATA CAAGAAGGGT AAAGACAGTC TTGCTGCTCA AGGAAAGCGT
           CGTTATGACC GTAAACAATC TGGTTATGGT GGTCAGACTA AGCCTGTCTT CCACAAAAAG
           gtaacattga ttatcatgca ttgattgttt tttcagtttg aattaggtct agttagttga
           aatgaggtag ttttaaggaa ccatttatag tagaattttg gaagtgagct gtgaggaaac
           agacattcca atagtctcag ttttggactg agatacatct tgtgaatctt gttaacagGC
           TAAGACCACG AAGAAGATTG TTTTGAGGCT TCAGTGTCAA AGCTGCAAGC ACTTTTCGCA
           GCGTCCTATC AAGgtgcata gaacatagat cagttcatta taccggattt gtaacttggt
           aatttgctta cattgtgttg gtttgttgtt tatttcagAG GTGCAAGCAT TTCGAGATCG
           GTGGTGACAA GAAGGGAAAG GGAACATCTC TGTTTTAAgt tggtttcatc ttattttctg
           cgatttttgt acttgctgga tttggaatcc atttgtttta gctctctcgt ataagattgt
           ctcatctttg cttgttaact ctatattttg aatcatcaag atatggtttt gctgttaatc
           attgaccttc gatatttttt tgccaatccg ttctctctac caacctaaga aaaaatcact
           aatatctcac attagagggt gcaaaatttg gaaggtctat atcattgtcc aattttctga
           gtcatacaaa ttctttcata tgattcattg aacaagacac tcatttactt ataaagcgca
           tttatatgtt cacatgattt gtacaaaact catgagactg catcaagcag aaagtattta
           tttatcttta catgtcaaag ctttgagaat taagcaatga cgaataccct aagttcacct
           ctgtccccgc gagttatgcg catggtatca tcaacatagg taacttcgaa atccccag
21         gacgccctat ctttgggttg aaaacttgag tttccttagc agcttttgtg atattttgaa
           tcatttttat gggatatgtt tgagttattt tgtttttacg atatggtatt ggtaatacat
           actagttact acatagtcgt agactttcat gtttatttac aaatggatac aggtttaaaa
           acatttactt gcgactattt gatacacgtt agttacctgt taaaccagat taaataaaac
           taaaccactt gcacttgtta attgttagtg cttcgttagt tgtaaagctg agtaattttg
           tttccactcg agagagagaa aatggatctt atcttctttt ttttttttat catcacatcg
           atcgagaagc ctagagttag ggcctagggg tccactctca tattaataac ataaatgatt
           tcttgtgtga tatagcttca ctgatttatc agatcttttt gcatttgggt cgacaaacaa
           gaaagaagaa gaaagcttca ATGGAGAAGA GTAATGGCCT TCGAGTGATT CTGTTTCCAC
           TTCCATTACA AGGCTGCATC AACCCCATGA TTCAGCTCGC CAAGATCCTC CACTCAAGAG
           GTTTCTCCAT CACTGTGATC CACACGTGCT TCAACGCGCC AAAAGCTTCA AGCCATCCTC
           TCTTCACCTT CTTAGAGATC CCAGATGGCT TGTCCGAAAC AGAGAAAAGA ACTAACAATA
           CCAAACTTCT CCTAACGCTT CTCAACCGGA ACTGTGAGTC TCCGTTTCGT GAATGTTTGA
           GTAAACTGTT GCAGTCTGCA GATTCAGAAA CAGGGGAAGA GAAACAGAGG ATTAGCTGTT
           TGATCGCTGA TTCTGGATGG ATGTTCACAC AACCCATTGC TCAGAGTTTG AAACTCCCAA
           TATTGGTCCT CAGTGTGTTT ACAGTCTCCT TCTTTCGCTG CCAATTTGTT CTTCCTAAGC
           TTCGGCGTGA AGTGTATCTT CCACTTCAAG gtattgttat ttcttacatt tttcgtatag
           accaagcaac tcgttaacct aaaaacatat atctaaattt tctcacagAT TCAGAACAGG
           AGGATCTAGT TCAAGAGTTT CCGCCGCTTC GAAAGAAGGA TATTGTACGT ATTCTTGATG
           TAGAAACAGA TATACTAGAT CCATTCTTGG ACAAAGTTCT ACAAATGACA AAGGCGTCTT
           CAGGTCTTAT ATTCATGTCA TGTGAAGAGT TGGACCACGA CTCAGTGAGT CAGGCACGTG
           AAGATTTCAA AATTCCTATC TTTGGGATTG GACCATCTCA CAGCCACTTT CCAGCTACCT
           CTAGTAGCTT GTCCACACCC GACGAGACTT GCATTCCATG GTTAGACAAA CAAGAAGACA
           AATCCGTGAT TTACGTCAGT TACGGGAGCA TCGTGACCAT CAGCGAATCA GATTTAATAG
           AGATTGCTTG GGGTCTAAGA AACAGCGACC AACCCTTCTT GTTGGTCGTA CGGGTTGGTT
           CAGTCCGTGG CAGAGAATGG ATCGAGACAA TCCCGGAAGA GATCATGGAA AAGCTTAATG
           AGAAGGGAAA GATAGTGAAA TGGGCTCCGC AACAAGACGT TCTAAAGCAT CGAGCCATTG
           GGGGATTCCT GACACATAAT GGTTGGAGCT CGACTGTTGA GAGTGTTTGT GAAGCAGTCC
           CTATGATCTG TTTGCCTTTT CGTTGGGACC AAATGCTAAA TGCAAGATTT GTTAGCGATG
           TATGGATGGT CGGGATAAAC CTAGAGGATC GGGTTGAAAG GAATGAGATC GAGGGAGCGA
           TAAGGAGATT ATTGGTGGAA CCTGAAGGAG AAGCCATCCG AGAGAGGATA GAACATCTTA
           AGGAGAAAGT AGGACGATCG TTTCAACAAA ACGGTTCCGC ATATCAATCG TTACAAAATT
           TGATTGATTA TATATCATCT TTTTAGccac tgacatgttg tttctttgtg ttttaagttt
           ttcaaccgat aaattgtttg tgtatcagaa atttcttcct ttgtgtgttt tgtattgtta
           gaataaaatt ttcttcgtaa gttggaattt acatatatac ttaccactta attatcagcc
           acgttttcag caacttttta ctattatttt gcaacctact aatacaaacg catcttgtct
           ttttatgtcc cttaactaat gaaaatcaaa tataaattag accactagtt acatgcccta
           gagggaaaac gaatctggtc tttctttatt agcacatcat gaagagtata gttttgtctc
           actctcgagt aataaagaat gcgaagtgct aataaagaaa gaccagattc ggaaatttct
           ttatgttata tatagatgtt tgttatcaaa agggaaagaa ttacaccatt cactgaaata
           tcaggagatt tacatttgga aagaaggtca aaaggagaaa gcttca
22         tattgttgat tctctatgcc gatttcgcta gatctgttta gcatgcgttg tggttttatg
           agaaaatctt tgttttgggg gttgcttgtt atgtgattcg atccgtgctt gttggatcga
           tctgagctaa ttcttaaggt ttatgtgtta gatctatgga gtttgaggat tcttctcgct
           tctgtcgatc tctcgctgtt atttttgttt ttttcagtga agtgaagttg tttagttcga
           aatgacttcg tgtatgctcg attgatctgg ttttaatctt cgatctgtta ggtgttgatg
           tttacaagtg aattctagtg ttttctcttt gagatctgtg aagtttgaac ctagttttct
           caataatcaa catatgaagc gatgtttgag tttcaataaa cgctgctaat cttcgaaact
           aagttgtgat ctgattcgtg tttacttcat gagcttatcc aattcatttc ggtttcattt
           tacttttttt ttagtgaaaa ATGGCCGATG GTGAGGATAT TCAGCCACTT GTCTGTGACA
           ATGGAACTGG AATGGTGAAG gtgagttaga ctgtttattt agatactgta tggttctaac
           cttctttgtt gtacatgtgt aagactactg atcatgattt ttgtatatta acagGCTGGT
           TTTGCTGGTG ATGATGCCCC GAGAGCAGTG TTCCCAAGTA TTGTTGGTCG TCCTAGGCAC
           ACTGGTGTCA TGGTTGGTAT GGGTCAGAAA GATGCTTACG TTGGTGATGA AGCTCAGTCC
           AAGAGAGGTA TCCTCACTCT GAAGTATCCA ATCGAACATG GTATTGTAAG TAACTGGGAT
           GACATGGAAA AGATATGGCA TCACACTTTC TACAACGAGC TTCGTGTTGC CCCTGAGGAG
           CACCCAGTTC TACTCACAGA GGCACCTCTT AACCCTAAAG CTAACAGGGA GAAGATGACT
           CAGATCATGT TTGAGACATT CAATGTCCCT GCCATGTATG TTGCCATTCA GGCCGTTCTT
           TCTCTCTATG CCAGTGGTCG TACAACCGgt tagttcttaa ctctaaacat ccaagtctga
           gttatattat cttcttactt gtatttactt aaagtcgttc tctttttgta acagGTATTG
           TGCTCGATTC TGGTGATGGT GTGTCTCACA CTGTGCCAAT CTACGAGGGG TATGCTCTTC
           CTCATGCTAT CCTTCGTCTT GATCTTGCGG GTCGGGATCT CACAGACTCA CTCATGAAGA
           TTCTCACTGA GAGAGGTTAC ATGTTCACCA CTACCGCAGA ACGGGAAATT GTCCGTGACA
           TAAAGGAGAA ACTTGCTTAT GTCGCTCTTG ACTACGAGCA AGAGCTAGAG ACAGCCAAGA
           GCAGTTCTTC AGTGGAGAAG AACTACGAGC TACCTGATGG ACAAGTCATA ACCATCGGAG
           CTGAGAGATT CCGTTGTCCT GAGGTTCTGT TCCAGCCATC GCTCATCGGA ATGGAAGCTC
           CTGGAATCCA TGAAACAACT TACAACTCCA TCATGAAATG TGATGTCGAT ATCAGGAAGG
           ATCTCTATGG AAACATCGTT CTCAGTGGTG GTTCCACCAT GTTCCCAGGA ATTGCTGACC
           GTATGAGCAA AGAGATCACC GCTCTTGCAC CTAGCAGCAT GAAGATCAAG GTGGTTGCAC
           CGCCAGAGAG AAAATACAGT GTCTGGATCG GAGGATCAAT CCTTGCATCC CTCAGCACCT
           TCCAACAGgt aaaaatccca attccgcctc tttaaaactt tcagctccat ttatgaaaca
           tgagtgaaaa tactgaaatt ttgttttgtt tgtgtgtgtg aatcagATGT GGATTTCAAA
           GAGTGAGTAC GATGAGTCAG GTCCATCGAT TGTTCACAGG AAATGCTTCT AAgtgtgtct
           tgtcttatct ggttcgtggt ggtgagtttg ttacaaaaaa atctattttc cctagttgag
           atgggaattg aactatctgt tgttatgtgg attttatttt cttttttctc tttagaacct
           tatggttgtg tcaagaagtc ttgtgtactt tagttttata tctctgtttt atctcttcta
           ttttctttag gatgcttgtg atgatgctgt ttttttttgt ccctaagcaa aaaaatatca
           tattatattt ggtccttggt tcattttttt ggtttttttt tgtcttcaca tataaatatt
           gtttgaatgt cttcaatctt ttatttgtat gagacaatta tttaagtatc gggtgacaat
           gcagctatta tgtattgtcg atttggatat tggcgcccaa aatatatact tagcctaaga
           atttggtaag tgagtggctt atgttttact ccagcaaaaa ttgtgtgtgt attaccattc
           tgatgcgaaa ca
23         aaaccatcta atctaagtct tgtctccttt atctacatat acggacaatt agatatcaca
           tgtacgaata tacaggcaat gtgggacaaa attcaaaaaa atgtgtctaa aaggggacaa
           gtggtcatta accttaattt aaattacggc caaatgttta gtaactaaat aaatatgggg
           tcgaaatgta aattctaaat tatctcacaa agtggggtac agaagtgaac actaataagt
           cataaagaga gatttaaagg agaaacgaaa agcattaaga tttaatttat atgaaattag
           tgaaaaccaa ccaaaaagaa tttatatgaa attctaaggg gcaaattgcg gaacaaagat
           tgtaaatagc aaaaggagtt tcagtataaa tatatgggga caagggccat aaaaataaca
           aaaacattct tagagagctt tggagataac gagaacaaga aagaaagaga agattatata
           catagaaaag gagagatcaa ATGGAGTGGG AGAAATGGTA CTTAGATGCG GTTCTTGTGC
           CAAGTGCTTT ACTTATGATG TTTGGTTACC ACATCTATTT GTGGTATAAG GTTCGAACCG
           ATCCTTTCTG CACCATTGTT GGTACAAATT CCCGCGCCCG TCGATCTTGG GTAGCAGCCA
           TCATGAAGgt agttatatta ctcaaaaacg atatatatcc cgaaataatc tttcaaaaat
           cttgtgttaa gtgattgtag taactagtaa gtagtaatta ctaattaatc atcatattag
           cgaaagtaat tagcttcatt gaacatatat accataatgt ttactaactg caatttttct
           atgaaaattg cttatgcaaa aacttagtat aggtgtcggc ccaaaatttt attaagtccg
           tatgaataca aaataaataa atttgcatgc atatttggcc aataagagac tataaatcca
           tacaatgtca taatatctct atgtatacat cattaacttt cttcatatat atgtacacag
           tatatacata gaattacttc tcaaatagta acaatatact gtgtctttgt tcagGACAAC
           GAGAAGAAGA ACATCTTAGC GGTACAAACA CTACGAAACA CGATAATGGG AGGGACGTTA
           ATGGCAACCA CTTGCATCCT CCTCTGCGCA GGTCTCGCTG CCGTTTTAAG CAGTACTTAT
           AGCATCAAGA AACCTTTAAA CGACGCCGTA TATGGAGCTC ATGGTGACTT CACTGTTGCA
           CTCAAATACG TAACCATCCT CACAATCTTC CTCTTCGCCT TCTTCTCTCA TTCTCTCTCC
           ATTCGCTTCA TCAACCAAGT CAACATCCTT ATTAACGCTC CTCAAGAACC TTTTTCTGAT
           GATTTCGGCG AAATAGGAAG CTTTGTGACT CCCGAGTATG TCTCTGAACT ACTCGAGAAA
           GCTTTCTTGC TCAATACGGT AGGTAATAGG CTGTTCTACA TGGGCTTGCC TTTGATGCTA
           TGGATCTTTG GGCCTGTGCT TGTGTTCTTG AGCTCTGCTT TGATAATCCC TGTTCTTTAT
           AACCTCGACT TCGTGTTTTT GTTGAGCAAT AAGGAGAAGG GTAAAGTCGA TTGCAATGGA
           GGTTGTGATG ACAACTTCTC GCCTTAAtta tctgttgatg ttgaattcga ataatgataa
           agctgtttgt tattactgat ttactagtct aaaaagtctt tcgatttact cttttcaaag
           cttaccaaaa aaaaaatgta ctagatccga gtcttttttt aatttttaat tttttttcct
           ggtgaagata ttcatgatct gctatatata attagtaaaa gttccatgga tagtcaaaat
           ggaaattaat taacaaaact atctttttta taaaattttt tattactatg ctgctaacaa
           gtaacaatga tgcgaccatc cttagtccct tacacttgat tcgtctatta ttttttctaa
           ttcaaatgtc aattttttaa tggcacagat actcgttttc aagtcaatgg agtgatactc
           atctgaattg gtcgtgtctt tttcctttat attagcccta tcagcggctt taataattat
           aacagacatt attatattga tgattattgg gatccaatga agaaagc
24         cattgttatt aagggaaatg aaatatctta actaaaccaa tttgttatct attgtgctct
           actgttctgt tcgtattgac tcgaacccac taaaccaaga cgagccctga ccgtcattgt
           ctaaattgac tcgaacccac taaagaaaaa aagaaaaaaa aacttagata ataattggcg
           cagaagggcc gattaataaa aactttaggc ccattaaagt aaagcttatt gtcaacccta
           tccagtctcc ttgtatatat ttatttacga caccaacgcg gcgttggtga ttcattctct
           tcagtcagag atttcgaaac cctagtcgat ttcgagatcc aaccaactct gctccttatc
           tcaggtaaaa ttctcgctcg agaactcaat tgcttatcca aagttccaat ggaagatgct
           ttcctactga atcttaggtt aatgttttgg atttggaatc ttacccgaaa tttctctgca
           gcttgttgaa tttgcgaagt ATGGGAGACG CTAGAGACAA CGAAGCCTAC GAGGAGGAGC
           TCTTGGACTA TGAAGAAGAA GACGAGAAGG TCCCAGATTC TGGAAACAAA GTTAACGGTG
           AAGCCGTGAA AAAgtgagtt ttatgatttc ctcgatctgt ttcatgagat agtggatgtt
           taaatttagg gttttcttag attactgctt gataacaacc gactaagttc ttcaattatc
           tatgtgtttg gttagttgct taactttatg acaattgact aagttcttca atgctaaaat
           tcctggaacc tacccaatat tagacggtca tgtgtttatc atcttgtatt ttctctttgt
           gacagAGGGT ACGTGGGAAT ACACAGTTCT GGATTCAGAG ACTTCCTTTT AAAACCGGAG
           CTTCTCAGAG CTATTGTTGA CTCTGGATTT GAACATCCAT CTGAAGgtta ttacaatgaa
           atacagcgta gctttgactt ttctgccttg cctttcacca ttctattacc gaatgatatt
           gtataattta cagaagtgac ttctccataa gatgttttag ttgtccggaa acttttaatt
           atatgtactt cgtctagttt tgagaagata tgttggttaa agatatttta tactttatct
           tggtcctttg cttatcatct aactaaatta aaaaaagttt gtgttgaggt caaattcttt
           tttatttcct gttataatgg tttttgtttt ctttgtttat taacgtttca ctgattactt
           tttccaggta ataaacgata tttcaatcta ttggtttgga gtgagcttaa acatgtgcta
           aagccaccaa tttaaaagat atggaggtta tcatctactt ataaaggctt tcttcggtac
           aattttcttt ggttctccac cagTGCAACA TGAATGTATC CCTCAAGCTA TCTTGGGCAT
           GGATGTCATC TGCCAAGCAA AGTCTGGTAT GGGGAAGACT GCTGTGTTTG TCCTGTCTAC
           TCTACAACAG ATTGAACCAT CTCCTGGCCA GGTTTCTGCA CTTGTCTTGT GCCATACAAG
           AGAGCTAGCT TACCAGgtat gaccttcttg tttcactcag gttcttggct tatagttttg
           ttgtacgtct tcttcctcta atgctttttg ccttgatgct gacaattact tgcagATCTG
           CAATGAGTTT GTGCGATTCA GTACCTATCT GCCTGATACA AAGGTTTCGG TGTTCTATGG
           TGGAGTCAAC ATTAAAATTC ACAAAGACTT GCTGAAGAAT GAATGTCCTC ACATTGTTGT
           TGGTACCCCT GGTCGGGTGC TTGCACTTGC CAGGGAGAAA GATCTCTCTT TGAAGAATGT
           GAGGCATTTT ATTCTTGATG AATGTGATAA AATGCTCGAG TCACTTGgta tgctgatttc
           tgacatcatt attacatcga tccctgaata attttatgtt ttaacacttt aacttttttt
           ttaccagACA TGCGAAGGGA TGTGCAGGAG ATTTTCAAGA TGACTCCTCA TGACAAACAA
           GTAATGATGT TCTCAGCAAC GCTCAGCAAA GAGATACGCC CAGTCTGCAA AAAATTTATG
           CAAGATgtaa tgttccatgg ccaattctct ctccctttgc aagtcttcta gttttcaact
           atttttagcc ttctatgagt gatcatagca ttagttgagc gtcttctgcg gttctgccct
           ggaaaagcgg caactgatct ctcaatgggt ctcaatccaa taatggttgg gtagtttgta
           gggaacgaga actgtgagtg tgagactctg tagctttggt atggtttcta tgggtgatta
           tagcattatt tgggcatctt ctgcggttct gccctggaaa agctgcaact gatctctcga
           tgggtctcaa tccactaatg ctttgggtag tttgtaggga tcgagaactg tgagtgtgag
           cctctgtagc attggtatga atgagtgacc attgcacaac aggatcttct ttcgtcatta
           ccttttattc agtttcaatt tctttgcaat tctagcagtg ctgggtgggt tttgggtggg
           gtactgtgtt gtcccaaggt ttcattgtga ttgtatgggc cttaatgttc cgagcaatat
           cgctgtatca tagcaaaact cacatctatg aagagaacct ggtggacgag gatctcagat
           caggggtttt acatccatct tcacttttgt agtgtaaatc atttcctgag aaaagcttgc
           taattattac ctgatatcta ttcctttcag CCAATGGAAA TATATGTCGA TGATGAAGCC
           AAGTTGACTC TTCATGGGCT TGTCCAGgta ctcttatctg gtgttaggtc ttcttattca
           atggaaatat agtttgttgt ttgatactta aaagaccttt tactgtcata ctgtaacagC
           ACTATATCAA ACTGAGCGAG ATGGAGAAAA CCCGGAAGTT GAATGACCTT CTTGATGCGT
           TGGACTTCAA TCAAGTTGTC ATTTTTGTGA AGAGCGTGAG CAGGGCTGCT GAGCTGAACA
           AGTTACTGGT GGAATGCAAT TTCCCCTCAA TATGCATCCA CTCTGGAATG TCTCAAGAAG
           AGAGgtctgt acattctctt caaaattcaa tgtttttgaa ggaccctacc tgctcttaaa
           gccctcatgg agaggagtcc aattcttaag gctaatacga tatgttatgt agGTTGACTC
           GATACAAAAG TTTCAAGGAA GGGCACAAAA GGATCCTTGT GGCGACTGAC TTGGTAGGAA
           GAGGGATTGA CATTGAGCGT GTCAACATTG TCATCAACTA TGACATGCCA GATTCTGCTG
           ATACCTATCT TCACAGGgta agtacataat actgaaattt attatttgat tgttgatctc
           actgaaaggg ctcttgtaac tttaccgttt tgctgtgtat ggtatagGTT GGCAGAGCTG
           GTAGATTTGG AACCAAGGGT CTTGCAATCA CATTTGTTGC ATCTGCTTCA GATTCAGAGG
           TTCTTAACCA Ggtatggtgt tcaatctttg taataagtcc acggaaaact cctcttgaaa
           ttgagttgga tatttagtaa agtggcaatt ataaatcttg gacagGTACA AGAGAGGTTT
           GAGGTTGATA TAAAGGAACT TCCGGAGCAG ATTGATACTT CAACCTACAG TAAGTGTGAA
           ATCCCTTACC AATTGTTTGT TTAAaagctt ggttttgtct ggttgtgata ttaatgttgt
           ttcttcttct ttctttgttc agtgccttct taaacaagta gcacgtccct caggaaagaa
           gctcttcaga tttcaacctt gtaggtgttc aaagggtcat gggggttcac aactatctct
           cgctccgttt gttttagtgt tttctatgac gacatttttt tccatatgtt tagaacgtct
           gttgtactct ttaaaggaga ttcgagtcac tctccaaatc gcacagttaa aagctgtcca
           gttttttgta caagagatta ttatgtttga aatatcagga tttagtctcg acctgattac
           tgtgttcctt aggaatcgat ctattatcaa tttatcatgg tgttgctaag aatcgtcatt
           catcagcgtt acttccttca tgtgatgctt tttttttata acacatttca tttagtgtgg
           aagagataca acacgtatat atggttactt tatatattga aaag
25         cttgtaagtt gttttccttt tgggatatgg gaagtgactt ctccgaccct tgcaaactaa
           caatggccat tacacactaa ttacaagcca aatttcctca ctaagcaacc tctcgtgttt
           atcataagac accgctctat ctcttattat tttattcatt gttttctaat ttcagactga
           ttaatcatac attagagaaa gtttattaaa accatctgat gtaaaaaatc acatttatct
           aaattaaata aatttgttat ctagtatata actatttatt gttttaacat ttggataaat
           tgtaagaaat tagaatgtaa aataagacag aaaatggtca actatgagca tctatcgcca
           tcatgatata gtttcgtcgt ttgcgttccc gacctaactc aaaacttcac caaccccatt
           tttaagcccc tttctttgtt tttatcctcc gatcgatcaa accaagaaaa aacactttcg
           tatttccctc gacgaaaaaa ATGGCAACCA TTTCGAATCT CGCTAATCTT CCCCGCGCCA
           CCTGCGTCGA CTCCAAATCT TCTTCCTCTT CCTCCGTCTT ACCTAGATCC TTCGTCAATT
           TCCGCGCTTT GAATGCAAAG CTTTCCTCTT CTCAGCTTTC TCTTCGTTAT AACCAACGAT
           CAATACCTTC CCTCTCgtaa gtctttatat ccatttgatg catgtctttt gtctctgttt
           ctcgctcttg gggttcacca aaaattgaat ctttttagct ggaaacgtac cacgaatctc
           aaagtaacat tttttataag atggattagg aaaagcaact gtatttcccc tttttggttg
           gtaaaagtct gatttttttg tttaatttgc agTGTGAGGT GTTCAGTGTC TGGTGGAAAT
           GGAACTGCTG GAAAGAGAAC GACTCTTCAT GATCTATATG AGAAGGAAGG TCAGAGTCCT
           TGGTATGATA ATCTTTGCCG TCCAGTCACA GATCTTCTCC CGTTGATTGC TCGTGGTGTT
           AGAGGTGTTA CTAGCAACCC TGCGgtaatt ttatcatctc tctttgtgtg tttggttttg
           cttttgctct gtgtttgttc atttgtcttt acttcttcac tttttataca tttgcagATC
           TTCCAAAAAG CCATTTCCAC TTCAAATGCT TATAATGATC AATTCAGgta tctttttgtg
           attgtcttag acttgtggtt gttaacaaca tgctattaaa actttagagt tcttctttat
           atgaaaagtt gtctgatatg ttaatggtat acctgacatg cactattagG ACACTTGTGG
           AATCGGGAAA GGACATTGAA AGTGCGTATT GGGAACTTGT GGTGAAGGAT ATTCAGGATG
           CCTGCAAACT TTTTGAGCCA ATCTATGACC AGACAGAAGG TGCGGATGGC TATGTCTCTG
           TTGAAGTTTC ACCTAGGCTT GCTGATGATA CCCAAGGAAC TGTTGAAGCT GCTAAATATC
           TTAGCAAGGT TGTCAACCGT CGTAATGTCT ACATTAAGAT TCCTGCTACT GCTCCATGCA
           TTCCTTCCAT CAGGGATGTC ATTGCAGCTG GAATAAGTGT CAATGTCACG gtaagttatc
           ctagtatgtt tcattattca agtttcttat tgcaagtttt aaagaacttc aaaataaaat
           aagtcataat acttcaaatt catgtattgt gtgatgatgt gctagatcac tggatttctt
           gggcgtttta aacctgaaac tagattagtt caagggtgtt ccaaggatgc actgatgtta
           ccttttctaa atcgtttctc atatgttctg ttctgtttca gCTTATATTC TCAATCGCCA
           GATATGAAGC AGTGATCGAT GCATATTTGG ATGGCCTCGA GGCGTCTGGA CTTGATGACC
           TCTCAAGAGT TACCAGTGTT GCTTCCTTCT TTGTCAGTCG GGTGGATACT CTCATGGACA
           AGATGCTTGA GCAAATTGGT ACCCCTGAAG CCTTAGATCT CCGTGGGAAG gtaaagctct
           attcatcgct gagatcttac accagccact gtgagtagag tattagctta tgacacatga
           tatgtttact cttgcagGCG GCTGTGGCTC AAGCTGCATT AGCATACAAG CTATACCAGC
           AGAAATTCTC TGGCCCAAGA TGGGAAGCTC TGGTAAAGAA AGGTGCCAAG AAACAGAGAC
           TTCTCTGGGC ATCAACAAGT GTAAAGAACC CAGCTTACTC TGACACCTTA TATGTCGCTC
           CTCTCATCGG ACCTGACACT gtaagtcatc tttttgtttg tgttgaagtc aataggctgt
           attaacgctt tggaagtata ttcatagttt ttgtgggtgt gatttagGTA TCAACCATGC
           CGGATCAAGC CCTGGAAGCA TTCGCAGATC ATGGAATAGT GAAGAGGACA ATAGATGCGA
           ATGTGTCAGA AGCAGAAGGG ATTTACAGTG CACTAGAGAA GCTGGGAATA GACTGGAACA
           AAGTAGGAGA ACAGTTGGAA GACGAAGGAG TAGATTCCTT CAAGAAGAGT TTCGAGAGTC
           TGCTCGGTAC ACTGCAAGAC AAGGCCAACA CTCTCAAACT AGCCAGCCAT TGAggaaatg
           agtcatcatt atgtttttgg ttacgctaaa ataaaaagaa gaacctttgg cttttgttct
           tcaatcctta tgcatgcttt ctaaagtggt tatgatggat tttgcttgat gttccacatt
           atgggttatt ctattttctt tgttcttgta agatgatgct tcagaagagt ttgttacttt
           ttaccgtatt tgtaatttac attttcactg aaaacaattg gcgagtaaaa aagtgtcctt
           gtcttcttct ttgttcggat tatatgaaca attgttccta gaagcctctc tacataaaaa
           gctgagactt tatctctcat ctctctttag acgtacaaaa aaatcagttt tttaagtttc
           actctaatgg cgtcaatttc gtcctttggc tgcttccctc aatccacagc gctcgccgga
           acttcctcca ccaccgtacg acgccgcacc atctctctgt ttcttcttct tcttcctttt
           tattcactga atc
26         attaagctct catttcggga agaattacta caaaagctac taatttgacc taattcatgc
           acaaatttga ttacaatgaa gaaataactt acaacgttga cgagcagaga aaccttgtag
           ccggtaattg tcggcgagag agcttctacc cttctggttg gattttttag ggttttagaa
           tttcattttc caacaaaaga taaacaaata aaaattggaa cttgtcgtta atacagccct
           ttaatgggtc aacgggtctt atgtctcttg aaaaagccca tgggccaaga caggtaaaat
           aacaatgtca ctttcgtaat tatcgcaaag tatatgcctt gttccatcag attccatttg
           cccaataaag cccgagtttc gagagttaat acctcattgg tgcttttggt tttggcaaag
           cgtgagtgag atcgggaatc aaacatcgcc tccgtctctc atttcaaacg ctatctccat
           ctccttcctc cgccgccgcc ATGGAATCTC CGAAGAATTC TCTGATCCCG AGCTTCCTCT
           ATTCATCATC TTCATCTCCG AGATCTTTCC TCCTCGACCA GGTGCTCAAT TCCAACTCCA
           ACGCTGCATT CGAGAAATCT CCTTCTCCGG CCCCGCGTTC CTCTCCTACG TCGATGATTT
           CTCGGAAGAA TTTCCTTATT GCATCTCCCA CCGAGCCAGG GAAGGGGATC GAGATGTATT
           CACCTGCCTT CTACGCTGCT TGTACCTTTG GTGGAATTCT CAGCTGTGGT CTTACTCACA
           TGACCGTGAC TCCTCTCGAT CTCGTCAAGT GCAATATGCA Ggtatgtaac ctttagatcc
           gttgtctttc gtttgttttc tgagctcatg tttgtggatc tgtgttcctg tgttgtttag
           gtagtgagat ctgtgttgct agatctgtga tttgattttc tttatcgctt tgttgttttc
           ctgactattg gttttgtgtt tgatttcaat atctgaagaa ttgtttgatc tctgataaac
           gcatcttcgt ctatccattt ccatgttata tatgaatcat tctatttcaa tatacgttaa
           tatggtctga tttctggttc ttctttcgaa atattgttac ttgacgtgtt atgtgttgaa
           tggttcactt ggtcttgcaa aactgatata tcttgttatc cagATTGATC CAGCGAAGTA
           CAAGAGCATC TCGTCTGGTT TTGGAATTTT GCTGAAAGAG CAAGGAGTCA AAGGCTTTTT
           CCGTGGATGG GTTCCTACTC TTTTGGGTTA CAGTGCTCAG GGTGCCTGCA AGTTTGGATT
           CTACGAGTAC TTTAAGAAGA CTTACTCTGA CCTTGCTGGA CCTGAGTACA CTGCCAAATA
           CAAGACTCTC ATCTACCTTG CTGGTTCTGC TTCTGCTGAG ATCATTGCCG ATATTGCACT
           TTGCCCATTT GAAGCTGTGA AGGTTCGTGT TCAGACACAG CCTGGATTTG CTAGGGGGAT
           GTCTGATGGA TTTCCCAAGT TTATCAAGTC CGAAGGATAC GGAGGgtgag tttttcaata
           ccaataacat tatctccctt gttactgcta gccttttggt ctgatttctg atttttttgc
           agCTTGTATA AGGGTCTTGC TCCACTCTGG GGACGTCAGA TTCCTTgtaa gttctggcct
           ctattttgca acctgttgca caatcttttt tttttttttt ttttgtttat tgatgaaaca
           tatgtagttc tttaaaagca aaaggtggtg atgatatcta tgaattttac agACACTATG
           ATGAAGTTTG CTTCCTTTGA GACCATTGTT GAGATGATTT ACAAGTACGC AATCCCCAAC
           CCAAAGAGTG AGTGCAGCAA AGGTCTGCAA CTCGGAGTGA GTTTTGCCGG AGGTTACGTT
           GCCGGAGTGT TCTGTGCCAT CGTTTCTCAT CCAGCAGACA ATCTAGTGTC ATTCCTCAAC
           AACGCTAAGG GAGCAACCGT TGGAGATgta agtcactatg tttgaataca atagcctaat
           gctagaatgg ctgtggtttg gtagttgtat acaagctatt gatttctgtt acggtagaaa
           taatatttaa tgtttgtaaa tgacatgttg cagGCGGTGA AGAAGATTGG TATGGTGGGA
           CTGTTCACAA GAGGGCTTCC TCTTAGAATT GTGATGATCG GGACGTTGAC TGGAGCACAG
           TGGGGATTAT ACGATGCCTT CAAAGTGTTT GTTGGCCTgt aagttcctct ctctcttcac
           ttactttcgt accttaattg taccttcaaa atgcaaaact ctcaattctt ttgatttggt
           attcagGCCA ACCACTGGTG GTGTTGCTCC AGCTCCTGCC ATCGCAGCTA CTGAAGCCAA
           AGCCTAAaca atgacgaaaa aggttattag gagttcgatg gggtaggatt tttgtttgga
           aaaataagag aaaccatacg gtgatgagga agagtgagta agctcaattt cttcctgatt
           tgaactttat catttttgtt ttttttgaaa tttgtgttcc tgaattcagg atagtgctct
           ctctctcttt acatactctc ttcctattgt ttcttgtcct ttttttcttt gtgtgatgta
           atcttaaaag atgagaggga cacactccaa gatagagaga gtgggcatac acccactcac
           tactttttat tcagtttcag ttgaaattct cttttggttg ctctatctat tattttactt
           ttttgtttta gagattatat aaaatctcgt tttaaaacat caaatcatag atagatcttg
           aatactaatc atatgtatac gtttaaccgc taagcgctaa cataaggaaa atattatgta
           ggcaaatgat taataaacat atgataa
27         aatgattttg acctttttaa ataatatatt caaatgtgtt tcaaacacga atcaaactat
           accaaaaaaa aaaaaaaagt tggataaaaa ataaaacctg actacacctc aactttggat
           caaaatctat gaatatattt tcaaaattat cttagtcaaa ttttaaatta attaattatt
           tatataaaat ttaataatta tcataacctt ggattaaatt tatctacagt caaaaattaa
           ttttaaatca attaattaat agcattatta caatccctaa ttgtacggga cgaataaaaa
           agtagaaaac tcaagttcct ttctttacca tacagctttt tcgattggag ttgaataagt
           cttcatctga cacgtgtaac cctggcacat gccgtccact aaaacacgtg cgagatctgt
           ataaatcaaa cctacgcgtt tcatctctct tttcaaaact caccgacgcg atccgatctc
           atctctctca tttcgaaacc ATGGTTGAGC CGGCGAATAC TGTTGGTCTT CCGGTGAACC
           CGACTCCGTT GCTGAAAGAT GAGCTCGATA TCGTGATTCC GACTATCAGA AACCTCGATT
           TCCTCGAGAT GTGGAGGCCT TTTCTTCAGC CTTACCATCT GATCATCGTC CAGGACGGAG
           ATCCATCGAA GAAGATCCAT GTCCCTGAAG GTTACGACTA CGAGCTCTAC AACAGGAACG
           ACATTAACCG AATCCTCGGA CCTAAGGCTT CTTGTATCTC GTTTAAGGAT TCTGCTTGTC
           GATGCTTTGG GTACATGGTG TCTAAGAAGA AGTATATCTT CACCATTGAT GACGATTGCT
           TCgtaagtta cttgaatttt gagttttgta ttcgttttta tgcttgattt gagagttttg
           tcaattttgg ttctagatct gtttttttga gcttatttgt ttgtgtttgt gtggattttt
           caagttcatt gcttgaattt cgtagatttg gtgagagatc aattatacga ttcactaaat
           ttgacggatc ttaggtttgt gagataatcc ttggttcgat tagctaggca attcaatgtt
           ttgtaccaga tccatagatc tgcttgttga gtctgaatat gttttcactt ttgtgtaatt
           agccatgatc tctaatgttt acttgtagat tttctgtgag ctgatgtctc ttttgttgac
           gacattgttg ttgagctgat atctctgagt cattatagct acctttacga tatggttgca
           cgtccttgtt catcactttt ttcttttgtt ttaccttttt gagatttgtg gggcatatcc
           aaggatgagt ctcgatgacg cttgtgttta gtttataatt ttctgagttt tttttggagg
           aactctttga tcaatggctt gatctggatt ttaaccgctt tttaattcat gtatttcttt
           gatgtgtaca tgtagGTTGC CAAGGATCCA TCAGGCAAAG CAGTGAACGC TCTTGAGCAA
           CACATCAAGA ACCTTCTCTG CCCATCGTCT CCCTTTTTCT TCAACACCTT GTATGATCCT
           TACCGTGAAG GTGCTGATTT CGTCCGTGGA TACCCTTTCA GTCTCCGTGA AGGTGTTTCC
           ACTGCTGTTT CCCATGGTCT TTGGCTCAAC ATCCCTGACT ACGATGCCCC GACCCAACTC
           GTGAAGCCTA AGGAGAGGAA CACCAGgtga caataattat catcataaca tgtttatgtg
           tttttttgtc aggatattca aatgtcagtt tttgctaaac gtttgatatg tcagGTATGT
           GGATGCTGTC ATGACCATCC CAAAGGGAAC ACTTTTCCCA ATGTGTGGTA TGAACTTGGC
           TTTTGACCGT GATTTGATTG GCCCGGCTAT GTACTTTGGT CTCATGGGTG ATGGTCAGCC
           TATTGGTCGT TACGACGATA TGTGGGCTGG TTGGTGCATC AAGgtaattt cttcttattc
           ccttgtaaga ctcataattg agtatagcta aatatgaagc acatgctctg tactaagcga
           tacctccatt tggggttgaa tcttttatag GTGATCTGTG ACCACTTGAG CTTGGGAGTG
           AAGACCGGTT TACCGTATAT CTACCACAGC AAAGCGAGCA ACCCTTTTGT TAACCTGAAG
           AAGGAATACA AGGGAATCTT CTGGCAGGAG GAGATCATTC CGTTCTTCCA GAACGCAAAG
           CTATCGAAAG AAGCAGTAAC TGTTCAGCAA TGCTACATTG AGCTCTCAAA GATGGTCAAG
           GAGAAGTTGA GCTCCTTAGA CCCGTACTTT GACAAGCTTG CAGATGCCAT GGTTACATGG
           ATTGAAGCTT GGGATGAGCT TAACCCACCA GCAGCCAGTG GCAAAGCTTG Agagcagtat
           gagccaaaaa gaaaaagcca ccaaagtttt ggttattttt agctcaaatt atcgttactt
           ttaaatttct gattttacga acctttcttg ctttttttac acatttgagt agttttcatc
           atcagtactt tctcattgtc cggttatggt ttttgcattt ggtttaaata tcaccggttt
           atttataaac agtggtggat tagtagtact attttctgag tttttttctt tgtttcatta
           ataaaaaggc cttttcatag gtgtttgcaa ttagtttttt tcccccatta atcatcgatt
           atcataggta tgttatggct ttaaatggta taaggaaatt gcttatagac caaaaaaaag
           ttgaattgct attgagagag cttttacaaa agaaagagca ttgttcaata agcttttcac
           atttggtcga tattttgatc aacctatcat aggtatctca attaataaac cggaatgtta
           atatgttttg c
28         ttctttaatt tcttcgccaa gaagagcacg aaatgtttgc caaacgcata tgcaacaacc
           ccacgttaca tatttctatt tgtagctata gagcaagcta tattgttaaa aactaaaaag
           aaaatcttta ctataacata tagatagagg attcgagata tcttgaaaga ctcaacttaa
           taaataaagt cgaaaagaaa acacggaggc gagaggacca cacactcgca cagaaagagt
           ctcatatcct ctataacaaa ttgataaact aaactaaaac gacacgtgat gtcttgatca
           gccaataaaa agctaccgac ataaggcaaa aatgatcgta ccattaaacg taatccacgt
           ggtttcagat tacacgtggc accacacaag tatctccatt tggcctataa atataaaccc
           ttaagcccac atatcttctc aatccatcac aaacaaaaca cacatcaaaa acgattttac
           aagaaaaaaa tatctgaaaa ATGTCAGAGA CCAACAAGAA TGCCTTCCAA GCCGGTCAGG
           CCGCTGGCAA AGCTGAGgta ctctttctct cttagaacag agtactgata gattgttcaa
           gttataactc tttgaaaaca gttgaaactt gatcactcct agaacttcca ttttcttgtt
           taatttagtt tgtcgtaatt atgtaattga ttttgtgttg accatggttg ttatatagGA
           GAAGAGCAAT GTTCTGCTGG ACAAGGCCAA GGATGCTGCT GCTGCAGCTG GAGCTTCCGC
           GCAACAGgta aacgatctat acacacatta tgacatttat gtaaagaatg aaaagtcttc
           ttagagcata catttacgca gatttctgat attttcatat ggtttgatgt aaatgttata
           gGCGGGAAAG AGTATATCGG ATGCGGCAGT GGGAGGTGTT AACTTCGTGA AGGACAAGAC
           CGGCCTGAAC AAGTAGcgat ccgagtcaac tttgggagtt ataatttccc ttttctaatt
           aattgttggg attttcaaat aaaatttggg agtcataatt gattctcgta ctcatcgtac
           ttgttgttgt ttttagtgtt gtaatgtttt aatgtttctt ctccctttag atgtactacg
           tttggaactt taagtttaat caacaaaatc tagtttaagt tctaagaact ttgttttacc
           atcctctttt ttattgcact taatgcttat agacttttat gtccatccat ttctcaattc
           ggctacgttg aattataagg gtcacataag caaaaaaata tcttaaaaag tcataacatt
           aaggcaaaga tagattctta aaagtactca aattgagatc acgaaaataa caagttagaa
           gttagaactt ccgtaggata tttataagaa caaaagatta ataaatgaag gcaatgattc
           tggattcctt gcaagttagg aagttcgaaa tcgttg
29         cgttattatt actacttcgc ttttagtgtg attcgtttca ttctcgtttt tttatattcc
           tcgatctgtt tgctcatttg ttgagatcta ttcgctatgt gagttcattt gactcagatc
           tggatatttc gtgttgttcg atttatagat ctggtttctg gatctgttta cgatctatcg
           tcatctttcc tttgaaaatg attggtgttt ctgtgttcgt attcgtttag atctaaagtt
           tttgatcgat gaatgtcgca tgtgttttta tctgaaagtt ttcgattaca gtatcaagtg
           gtggtagtag tagtagtaga ctcaaaaagc tgcacaaact ttttatacac gtgaattgtg
           attgctttac ggttttcttg gagtttgtta attaaatcat ttaatattaa gaagtttatg
           aattaagaga acgttatttt atactatgat tttgattttg atttggtttg tgtgttttaa
           tgcagtaaaa gaaaatcaaa ATGGCTTCAC ACATTGTTGG ATACCCACGT ATGGGCCCTA
           AGAGAGAGCT CAAGTTTGCA TTGGAATCTT TCTGGGATGG TAAGAGCACT GCTGAGGATC
           TTCAGAAGGT GTCTGCTGAT CTCAGGTCAT CCATCTGGAA ACAGATGTCT GCCGCTGGGA
           CTAAGTTCAT CCCTAGCAAC ACCTTTGCTC ACTACGACCA GGTTCTTGAC ACCACCGCCA
           TGCTCGGTGC TGTTCCACCT AGGTATGGAT ACACTGGTGG TGAGATCGGC CTTGATGTTT
           ACTTCTCCAT GGCTAGAGGA AATGCCTCTG TGCCTGCCAT GGAAATGACC AAGTGGTTCG
           ACACCAACTA gtgagtcttc attgatctct tgtgttcttt ttgttgacat tggtcttttt
           gagttgtgga ctaatttgat tatgcttttg ttgatgcagC CATTACATCG TCCCTGAGTT
           GGGCCCTGAG GTTAACTTCT CTTACGCATC CCACAAGGCG GTGAATGAGT ACAAGGAGGC
           CAAGGCTgta cgtatcattc tttactaata tccgtttctt aggaaattac tgtttgctcg
           tctaattaac tattagagat cataggcttt agtttgagga tatagtgttt aagcttagat
           tcattgagtg gtgtttcact gaggatgcta atatgctagg aaggtctcgg atgcattgaa
           tataaaaacc gttagaaaag tcatctggca ctggttgtct aaagtagttt ttttttctac
           gaagttctga tctggtttac ttgatgttta tgcagCTTGG TGTTGACACC GTCCCTGTAC
           TTGTTGGCCC AGTCTCTTAC TTGCTGCTTT CCAAGGCTGC CAAGGGTGTT GACAAGTCAT
           TCGAACTTCT TTCTCTTCTC CCTAAGATTC TCCCGATCTA CAAgtaagaa atcactttat
           tgtttttctt tattatgcca tccgtatcct tgatgttatc aatgatcctc tgacatacca
           ctgatataat gactttgatt tgtgtacagG GAAGTGATTA CCGAGCTTAA GGCTGCTGGT
           GCCACCTGGA TTCAGCTTGA CGAGCCTGTC CTTGTTATGG ATCTTGAGGG TCAGAAACTC
           CAGGCCTTTA CTGGTGCCTA TGCTGAACTT GAATCAACTC TTTCTGGTTT GAATGTTCTT
           GTCGAGACCT ACTTCGCTGA TATCCCTGCT GAGGCATACA AGACCCTAAC CTCATTGAAG
           GGTGTGACTG CCTTTGGATT TGATTTGGTT CGTGGCACCA AGACCCTTGA TTTGGTCAAG
           GCAGGTTTCC CTGAGGGAAA GTACCTCTTT GCTGGTGTTG TTGATGGAAG GAACATCTGG
           GCCAACGACT TTGCTGCGTC CCTAAGCACC TTGCAGGCAC TTGAAGGCAT TGTTGGTAAA
           Ggtaattgtt cttccaaaat catctgcctt ttacctgaca ttactaggga attattgaaa
           aacaactgta tgaaatgttg atctgttgtc tttttgatgc agACAAGCTT GTGGTCTCAA
           CCTCCTGCTC TCTTCTCCAC ACCGCTGTTG ATCTTATCAA TGAGACTAAG CTTGATGATG
           AAATCAAGTC ATGGTTGGCG TTTGCTGCCC AGAAGGTCGT TGAAGTGAAC GCTTTGGCCA
           AGGCTTTGGC TGGTCAGAAG GACGAGgtat tttacccaca tgctccccta gtagtggacc
           cttgaattat ctgtagtgta attgatccag aaaaatctag aactcaatat tttttttctt
           tcagGCTCTT TTCTCTGCCA ATGCTGCGGC TTTGGCTTCA AGGAGATCTT CCCCAAGAGT
           CACCAACGAG GGTGTCCAGA AGGCTgtaag tttgatttca aactgatgca ctgtgctcac
           ccaatggttt attttcctaa tcttgtattg attgagatag tttctcattc ttgttatctc
           agGCTGCTGC TTTGAAGGGA TCTGACCACC GTCGTGCAAC CAATGTTAGT GCTAGGCTAG
           ATGCTCAGCA GAAGAAGCTC AATCTCCCAA TCCTACCAAC CACAACCATT GGATCCTTCC
           CACAGACTGT AGAGCTCAGG AGAGTTCGTC GTGAGTACAA GGCCAAAAAg ttagtctcct
           aaatttaatc cttgggctta tgcgtcacac attttcttaa attgttgtga tgctaatggt
           ttctttaatc tctcttttac tagGGTCTCA GAGGAGGACT ACGTTAAAGC CATCAAGGAA
           GAGATCAAGA AAGTTGTTGA CCTCCAAGAG GAACTTGACA TCGATGTTCT TGTCCACGGA
           GAGCCAGAGg tgaatttttt ttattattct atgtttttgc ctgatatttc tagtaatcct
           tggtactgtt tctgatgaga catgttttca caattttgta gAGAAACGAC ATGGTTGAGT
           ACTTTGGTGA GCAGTTGTCT GGTTTTGCCT TCACTGCAAA CGGATGGGTC CAATCTTATG
           GATCTCGCTG TGTGAAGCCA CCAGTTATCT ATGGTGATGT GAGCCGTCCC AAGGCAATGA
           CCGTCTTCTG GTCCGCAATG GCTCAGAGCA TGACCTCTCG CCCAATGAAG GGTATGCTTA
           CTGGTCCCGT CACCATTCTC AACTGGTCCT TTGTCAGGAA CGACCAGCCC AGgtacataa
           tgttactata atctaaaaac aaacataaac accaaataaa gaacaaaaca ctaagacaat
           cttggaatca ttgtagGCAC GAAACCTGTT ACCAGATCGC TTTGGCCATC AAGGACGAAG
           TCGAGGATCT TGAGAAAGGT GGAATCGGTG TCATTCAGAT TGATGAGGCT GCACTTAGAG
           AAGGACTACC ACTCAGGAAA TCCGAGCATG CTTTCTACTT GGACTGGGCC GTCCACTCCT
           TCAGAATCAC CAACTGTGGA GTCCAAGACA GCACCCAGgt ttgcttaaat aaaaactaca
           cataacgagt ctcatgtagt gtaatgcttt ctcagttgct cataacttat gtgtttctgg
           tgtttttttt ttgcagATCC ACACTCACAT GTGCTACTCC CACTTCAATG ACATCATACA
           CTCCATCATC GACATGGATG CTGATGTCAT CACCATTGAG AACTCCAGGT CTGATGAGAA
           GCTTCTTTCC GTGTTCCGTG AAGGAGTGAA GTACGGTGCT GGAATCGGTC CAGGAGTCTA
           CGACATCCAC TCTCCAAGAA TACCATCTTC TGAGGAAATC GCAGACAGGG TCAACAAGAT
           GCTTGCTGTC CTAGAGCAGA ACATCCTTTG GGTTAACCCT GACTGTGGTC TCAAGACCCG
           TAAGTACACC GAGGTCAAGC CTGCACTCAA GAACATGGTT GATGCGGCTA AGCTCATCCG
           CTCCCAGCTC GCCAGTGCCA AGTGAagaaa agcttgattt gaacaaggaa acgttttttt
           ttctctaaaa tggttgtgtt ttatttggtt taataacttt cttaaaaata tttttagtcg
           aaggtagatt tgatgcatat ggtttctttc ttgttgagag agagaaaggc tatagcatcc
           tttggatttg atgcaatgtt tgtgattttc tttttgtctc caatatattt ctctgatgga
           atgtcttttt tctaaagtat cttgaaaagg aataagagga ttgattctta tacaaatact
           tttgtttgcg ttgtcctaaa ctcactactt ttttttatcc gacgcaatca gtgctttgta
           gcctgttctt gaagtaggcc cctttgtatg tctctatctg gctcctgtat cagattgttg
           tttcccttag atttctttat ttcgttggca aaaagaaaat ctgaattgcc ccacaaagag
           cgtggtggct gatgttaggt tgcagtctca tggtccacca cttta
30         ttttgcagaa acattacatt acagatggag aacgccaaaa atcgattctt ttttttaatt
           ttcttttttg acaaatcgca ttctgcacac attccttttt tttttaattt tctccactac
           accactaatc ttgccgtgat aggtgcatgt gtatgtgttt aagacatatc tcttttgttc
           cggttggatt agtttatgta ataaccaaca actatactta atacattttg tccacttttg
           aattttctgt ttcttatttt gtttactgta aaaaagaatg aaaatcattg agatattaaa
           actaactaat cactaaggcc catttagtag acccaataag gcccatatgc tatttttttt
           ctccagaatt tgacctttat gtatttgacc gagtggaaaa gtaatacagt tcttttcttc
           tctcctcctc tttcttcttc atgattggaa ttttagggct tttgaaagca cgaacgcgtg
           aagctctaat cgagaaaaaa ATGGAGGTTT TGGATAGGAG AGACGATGAG ATCAGGGACT
           CGGGAAACAT GGACAGCATC AAGTCACACT ATGTTACCGA CTCTGTTTCC GAGGAACGCC
           GCTCTCGTGA GCTCAAGGAT GGAGACCATC CTTTACGGgt ttgtccttta tccttagtat
           cgattcattt gcaatttgaa tctgatctta gctgaaaatt tgattcccgt tcgtcaaaga
           tttctgaact ggtgatatga cggtttatag ctagagtagt ggaagattcg gattctaaat
           ctttgtttgt tggagttttt gttttcaaat taggttttgc gaatttgttt agatgtatgt
           gagctcaaat gttataggat tttcgtattg gtggtattga ttgtagctag aacaaggcag
           attgatttag aggaactgat ttcattgtta agagtaagta ctggctcagt gactctagga
           tttttggtaa tgatgcagTA CAAGTTTTCG ATATGGTACA CTCGTCGCAC ACCAGGGGTT
           CGGAACCAGT CTTATGAAGA TAACATCAAG AAGATGGTAG AATTCAGCAC Ggtaagtcta
           aatatactac tggaagttca ttgttgaagc tgtttgcgat actatcttgt tcgtttctga
           gttatggctt ttataaacta gGTTGAAGGA TTTTGGGCCT GCTACTGTCA CCTTGCTCGT
           TCTTCTCTCT TGCCTAGTCC AACAGATCTT CATTTCTTTA AGGATGGGAT TCGTCCATTG
           TGGGAGgtac gtattcccct gtgttgattt ttcgtattgt gtttttatct ggatcatcga
           tatagaggga accttttata caacaaaagt ttctcaagag ttgtatcttc ttcaataaac
           caactaaact agctaaattc atcaccttta gGATGGTGCC AACTGCAATG GAGGAAAGTG
           GATCATACGT TTCTCAAAAG TTGTATCTGC TCGCTTCTGG GAGGATCTGg tgagttttat
           tttcttgtgg gcactactat tggagtattg acacctttct actttattca aaagaaaccc
           ttttgtcaat gttatttata atccatttta catacttagg gtctgagaat catgttaaat
           actcttccgt ttatttgttt tcttcagCTT CTTGCGTTGG TAGGCGACCA GCTTGATGAT
           GCTGATAACA TATGTGGGGC AGTACTGAGT GTCCGTTTCA ACGAGGACAT CATTAGTGTA
           TGGAATCGCA ATGCTTCTGA CCATCAGgtg agaaaactgt tcacaagaag aactgtctct
           ctccctctcc ttttgattgg tacttacaca gtgcaatgtt ttccttaaac agGCAGTGAT
           GGGTTTGAGA GACTCAATCA AGCGGCATTT GAAGTTGCCT CATGCATATG TCATGGAATA
           CAAGCCACAC GATGCTTCTC TCCGCGACAA CTCTTCCTAC AGAAACACAT GGCTGAGAGG
           ATAGgcccaa agtcgatgat tgtatcatgt aatgtggaga agatttggga agctcatctg
           caacctggga agatatctgg attgaaccct gtatccaata ccatactgta ccggaggctt
           acaatatcag aaaaaacaaa atccgggcta cttctgtgtc agtatgtgtt catttcgttt
           ttcttttaca gtacatcttg ttaacttcaa tggtttgact cttgatcaaa actataagga
           tgtattttca atgaaaactg gaaattacgt tctggtttac attataactc atgtcttaaa
           aagtaacagg atgtcaatat acaatgtcac ttcgtacgat gatctctaat gtacatctac
           tgatgaaaaa ctgagtgtgg ctctgtccgt tgatctcaaa agctatagtt tagcatccgc
           agatgattga agtccgatga tacctggttc aacatcaaag cctcgagtga attacttcac
           acaatggaaa ctagaaaata agag
31         MALKSKLVSL LFLIATLSST FAASFSDSDS DSDLLNELVS LRSTSESGVI HLDDHGISKF
           LTSASTPRPY SLLVFFDATQ LHSKNELRLQ ELRREFGIVS ASFLANNNGS EGTKLFFCEI
           EFSKSQSSFQ LFGVNALPHI RLVSPSISNL RDESGQMDQS DYSRLAESMA EFVEQRTKLK
           VGPIQRPPLL SKPQIGIIVA LIVIATPFII KRVLKGETIL HDTRLWLSGA IFIYFFSVAG
           TMHNIIRKMP MFLQDRNDPN KLVFFYQGSG MQLGAEGFAV GFLYTVVGLL LAFVTNVLVR
           VKNITAQRLI MLLALFISFW AVKKVVYLDN WKTGYGIHPY WPSSWR*
32         MTKTMMIFAA AMTVMALLLV PTIEAQTECV SKLVPCFNDL NTTTTPVKEC CDSIKEAVEK
           ELTCLCTIYT SPGLLAQFNV TTEKALGLSR RCNVTTDLSA CTAKGAPSPK ASLPPPAPAG
           NTKKDAGAGN KLAGYGVTTV ILSLISSIFF *
33         MAAITEFLPK EYGYVVLVLV FYCFLNLWMG AQVGRARKRY NVPYPTLYAI ESENKDAKLF
           NCVQRGHQNS LEMMPMYFIL MILGGMKHPC ICTGLGLLYN VSRFFYFKGY ATGDPMKRLT
           IGKYGFLGLL GLMICTISFG VTLILA*
34         MSLLADLVNL DISDNSEKII AEYIWVGGSG MDMRSKARTL PGPVTDPSKL PKWNYDGSST
           GQAPGQDSEV ILYPQAIFKD PFRRGNNILV MCDAYTPAGE PIPTNKRHAA AEIFANPDVI
           AEVPWYGIEQ EYTLLQKDVN WPLGWPIGGF PGPQGPYYCS IGADKSFGRD IVDAHYKASL
           YAGINISGIN GEVMPGQWEF QVGPSVGISA ADEIWIARYI LERITEIAGV VVSFDPKPIP
           GDWNGAGAHT NYSTKSMREE GGYEIIKKAI EKLGLRHKEH ISAYGEGNER RLTGHHETAD
           INTFLWGVAN RGASIRVGRD TEKEGKGYFE DRRPASNMDP YVVTSMIAET TLLWNP*
35         MYQKFQISGK IVKTLGLKMK VLIAVSFGSL LFILSYSNNF NNKLLDATTK VDIKETEKPV
           DKLIGGLLTA DFDEGSCLSR YHKYFLYRKP SPYKPSEYLV SKLRSYEMLH KRCGPDTEYY
           KEAIEKLSRD DASESNGECR YIVWVAGYGL GNRLLTLASV FLYALLTERI ILVDNRKDVS
           DLLCEPFPGT SWLLPLDFPM LNYTYAWGYN KEYPRCYGTM SEKHSINSTS IPPHLYMHNL
           HDSRDSDKLF VCQKDQSLID KVPWLIVQAN VYFVPSLWFN PTFQTELVKL FPQKETVFHH
           LARYLFHPTN EVWDMVTDYY HAHLSKADER LGIQIRVFGK PDGRFKHVID QVISCTQREK
           LLPEFATPEE SKVNISKTPK LKSVLVASLY PEFSGNLTNM FSKRPSSTGE IVEVYQPSGE
           RVQQTDKKSH DQKALAEMYL LSLTDNIVTS ARSTFGYVSY SLGGLKPWLL YQPTNFTTPN
           PPCVRSKSME PCYLTPPSHG CEADWGTNSG KILPFVRHCE DLIYGGLKLY DEF*
36         MRTVVHDLAV VLLVIFYDYY MLFILDRLLE ANYGGKWEKI LGNHVDIFKN YPLIGQLFVQ
           DMYNSIMDFP SFFIFQALLE YERHKVSEGE LQIPLPLELE PMNIDNQASG SGRARRDAAS
           RAMQGWHSQR LNGNGEVSDP AIKDKNLVLH QKREKQIGTT PGLLKRKRAA EHGAKNAIHV
           SKSMLDVTVV DVGPPADWVK INVQRTQDCF EVYALVPGLV REEVRVQSDP AGRLVISGEP
           ENPMNPWGAT PFKKVVSLPT RIDPHHTSAV VTLNGQLFVR VPLEQLE*
37         MSWQSYVDDH LMCDVEGNHL TAAAILGQDG SVWAQSAKFP QLKPQEIDGI KKDFEEPGFL
           APTGLFLGGE KYMVIQGEQG AVIRGKKGPG GGVIKKTNQA LVFGFYDEPM TGGQCNLVVE
           RLGDYLIESE L*
38         MYVVKRDGRQ ETVHFDKITA RLKKLSYGLS SDHCDPVLVA QKVCAGVYKG VTTSQLDELA
           AETAAAMTCN HPDYASLAAR IAVSNLHKNT KKSFSETIKD MFYEVNDRSG LKSPLIADDV
           FEIIMQNAAR LDSEIIYDRD FEYDYFGFKT LERSYLLKVQ GTVVERPQHM LMRVAVGIHK
           DDIDSVIQTY HLMSQRWFTH ASPTLFNAGT PRPQLSSCFL VCMKDDSIEG IYETLKECAV
           ISKSAGGIGV SVHNIRATGS YIRGTNGTSN GIVPMLRVFN DTARYVDQGG GKRKGAFAVY
           LEPWHADVYE FLELRKNHGK EEHRARDLFY ALWLPDLFME RVQNNGQWSL FCPNEAPGLA
           DCWGAEFETL YTKYEREGKA KKVVQAQQLW YEILTSQVET GTPYMLFKDS CNRKSNQQNL
           GTIKSSNLCT EIIEYTSPTE TAVCNLASIA LPRFVREKGV PLDSHPPKLA GSLDSKNRYF
           DFEKLAEVTA TVTVNLNKII DVNYYPVETA KTSNMRHRPI GIGVQGLADA FILLGMPFDS
           PEAQQLNKDI FETIYYHALK ASTELAARLG PYETYAGSPV SKGILQPDMW NVIPSDRWDW
           AVLRDMISKN GVRNSLLVAP MPTASTSQIL GNNECFEPYT SNIYSRRVLS GEFVVVNKHL
           LHDLTDMGLW TPTLKNKLIN ENGSIVNVAE IPDDLKAIYR TVWEIKQRTV VDMAADRGCY
           IDQSQSLNIH MDKPNFAKLT SLHFYTWKKG LKTGMYYLRS RAAADAIKFT VDTAMLKEKP
           SVAEGDKEVE EEDNETKLAQ MVCSLTNPEE CLACGS*
39         MAYASRFLSR SKQLQGGLVI LQQQHAIPVR AFAKEAARPT FKGDEMLKGV FFDIKNKFQA
           AVDILRKEKI TLDPEDPAAV KQYANVMKTI RQKADMFSES QRIKHDIDTE TQDIPDARAY
           LLKLQEIRTR RGLTDELGAE AMMFEALEKV EKDIKKPLLR SDKKGMDLLV AEFEKGNKKL
           GIRKEDLPKY EENLELSMAK AQLDELKSDA VEAMESQKKK EEFQDEEMPD VKSLDIRNFI
           *
40         MHGYEDDLDE EAGYDDYYSG DEDEYEDEEE EDEEPPKEEL EFLESRQKLK ESIRKKMGNG
           SANAQSSQER RRKLPYNDFG SFFGPSRPVI SSRVIQESKS LLENELRKMS NSSQTMFLLM
           ELFFGVQKKR PVPTNGSGSK NVSQEKRPKV VNEVRRKVET LKDTRDYSFL FSDDAELPVP
           KKESLSRSGS FPNSAYHFHE DNLYRFFADV QEARSAQLSS RPKQSSGING RTAHSPHREE
           KRPVSANGHS RPSSSGSQMN HSRPSSSGSK MNHSRPATSG SQMPNSRPAS SGSQMQSRAV
           SGSGRPASSG SQMQNSRPQN SRPASAGSQM QQRPASSGSQ RPASSGSQRP ASSGSQRPGS
           STNRQAPMRP PGSGSTMNGQ SANRNGQLNS RSDSRRSAPA KVPVDHRKQM SSSNGVGPGR
           SATNARPLPS KSSLERKPSI SAGKSSLQSP QRPSSSRPMS SDPRQRVVEQ RKVSRDMATP
           RMIPKQSAPT SKHQMMSKPA LKRPPSRDID HERRLLKKKK PARSEDQEAF DMLRQLLPPK
           RFSRYDDDDI NMEAGFEDIQ KEERRSARIA REEDERELKL LEEEERRERL KKNRKLSR*
41         MDPNQRIARI SAHLNPPNLH NQIADGSGLN RVACRAKGGS PGFKVAILGA AGGIGQPLAM
           LMKMNPLVSV LHLYDVANAP GVTADISHMD TSAVVRGFLG QPQLEEALTG MDLVIIPAGV
           PRKPGMTRDD LFNINAGIVR TLSEAIAKCC PKAIVNIISN PVNSTVPIAA EVFKKAGTFD
           PKKLMGVTML DVVRANTFVA EVMSLDPREV EVPVVGGHAG VTILPLLSQV KPPCSFTQKE
           IEYLTDRIQN GGTEVVEAKA GAGSATLSMA YAAVEFADAC LRGLRGDANI VECAYVASHV
           TELPFFASKV RLGRCGIDEV YGLGPLNEYE RMGLEKAKKE LSVSIHKGVT FAKK*
42         MAQVQAPSSH SPPPPAVVND GAATASATPG IGVGGGGDGV THGALCSLYV GDLDFNVTDS
           QLYDYFTEVC QVVSVRVCRD AATNTSLGYG YVNYSNTDDA EKAMQKLNYS YLNGKMIRIT
           YSSRDSSARR SGVGNLFVKN LDRSVDNKTL HEAFSGCGTI VSCKVATDHM GQSRGYGFVQ
           FDTEDSAKNA TEKLNGKVLN DKQIFVGPFL RKEERESAAD KMKFTNVYVK NLSEATTDDE
           LKTTPGQYGS ISSAVVMRDG DGKSRCFGFV NFENPEDAAR AVEALNGKKF DDKEWYVGKA
           QKKSERELEL SRRYEQGSSD GGNKFDGLNL YVKNLDDTVT DEKLRELFAE FGTITSCKVM
           RDPSGTSKGS GFVAFSAASE ASRVLNEMNG KMVGGKPLYV ALAQRKEERR AKLQAQFSQM
           RPAFIPGVGP RMPIFTGGAP GLGQQIFYGQ GPPPIIPHQP GFGYQPQLVP GMRPAFFGGP
           MMQPGQQGPR PGGRRSGDGP MRHQHQQPMP YMQPQMMPRG RGYRYPSGGR NMPDGPMPGG
           MVPVAYDMNV MPYSQPMSAG QLATSLANAT PAQQRTLLGE SLYPLVDQIE SEHAAKVTGM
           LLEMDQTEVL HLLESPEALN AKVSEALDVL RNVNQPSSQG SEGNKSGSPS DLLASLSIND
           HL*
43         MAENYDRASE LKAFDEMKIG VKGLVDAGVT KVPRIFHNPH VNVANPKPTS TVVMIPTIDL
           GGVFESTVVR ESVVAKVKDA MEKFGFFQAI NHGVPLDVME KMINGIRRFH DQDPEVRKMF
           YTRDKTKKLK YHSNADLYES PAASWRDTLS CVMAPDVPKA QDLPEVCGEI MLEYSKEVMK
           LAELMFEILS EALGLSPNHL KEMDCAKGLW MLCHCFPPCP EPNRTFGGAQ HTDRSFLTIL
           LNDNNGGLQV LYDGYWIDVP PNPEALIFNV GDFLQLISND KFVSMEHRIL ANGGEEPRIS
           VACFFVHTFT SPSSRVYGPI KELLSELNPP KYRDTTSESS NHYVARKPNG NSSLDHLRI*
44         MYKLDRKLGK GGFGQVYVGR KMGTSTSNAR FGPGALEVAL KFEHRTSKGC NYGPPYEWQV
           YNALGGSHGV PRVHFKGRQG DFYVMVMDIL GPSLWDVWNS TTQAMSTEMV ACIAIEAISI
           LEKMHSRGYV HGDVKPENFL LGPPGTPEEK KLFLVDLGLA SKWRDTATGL HVEYDQRPDV
           FRGTVRYASV HAHLGRTCSR RDDLESLAYT LVFLLRGRLP WQGYQVGDTK NKGFLVCKKK
           MATSPETLCC FCPQPFRQFV EYVVNLKFDE EPDYAKYVSL FDGIVGPNPD IRPINTEGAQ
           KVIW*
45         MAQRLEAKGG KGGNQWDDGA DHENVTKIHV RGGLEGIQFI KFEYVKAGQT VVGPIHGVSG
           KGFTQTFEIN HLNGEHVVSV KGCYDNISGV IQALQFETNQ RSSEVMGYDD TGTKFTLEIS
           GNKITGFHGS ADANLKSLGA YFTPPPPIKQ EYQGGTGGSP WDHGIYTGIR KVYVTFSPVS
           ISHIKVDYDK DGKVETRQDG DMLGENRVQG QPNEFVVDYP YEYITSIEVT CDKVSGNTNR
           VRSLSFKTSK DRTSPTYGRK SERTFVFESK GRALVGLHGR CCWAIDALGA HFGAPPIPPP
           PPTEKLQGSG GDGGESWDDG AFDGVRKIYV GQGENGIASV KFVYDKNNQL VLGEEHGKHT
           LLGYEEFELD YPSEYITAVE GYYDKVFGSE SSVIVMLKFK TNKRTSPPYG MDAGVSFILG
           KEGHKVVGFH GKASPELYQT GVTVAPITK*
46         MDIEKAGSRR EEEEPIVQRP RLDKGKGKAH VFAPPMNYNR IMDKHKQEKM SPAGWKRGVA
           IFDFVLRLIA AITAMAAAAK MATTEETLPF FTQFLQFQAD YTDLPTMSSF VIVNSIVGGY
           LTLSLPFSIV CILRPLAVPP RLFLILCDTV MMGLTLMAAS ASAAIVYLAR NGNSSSNWLP
           VCQQFGDFCQ GTSGAVVASF IAATLLMFLV ILSAFALKRT T*
47         MTTEEKEILA AKLEEQKIDL DKPEVEDDDD NEDDDSDDDD KDDDEADGLD GEAGGKSKQS
           RSEKKSRKAM LKLGMKPITG VSRVTVKKSK NILFVISKPD VFKSPASDTY VIFGEAKIED
           LSSQIQSQAA EQFKAPDLSN VISKGESSSA AVVQDDEEVD EEGVEPKDIE LVMTQAGVSR
           PNAVKALKAA DGDIVSAIME LTT*
48         MLPSDAADPS VCYVPNPYNP YQYYNVYGSG QEWTDYPAYT NPEGVDMNSG IYGENGTVVY
           PQGYGYAAYP YSPATSPAPQ LGGEGQLYGA QQYQYPNYFP NSGPYASSVA TPTQPDLSAN
           KPAGVKTLPA DSNNVASAAG ITKGSNGSAP VKPTNQATLN TSSNLYGMGA PGGGLAAGYQ
           DPRYAYEGYY APVPWHDGSK YSDVQRPVSG SGVASSYSKS STVPSSRNQN YRSNSHYTSV
           HQPSSVTGYG TAQGYYNRMY QNKLYGQYGS TGRSALGYGS SGYDSRTNGR GWAATDNKYR
           SWGRGNSYYY GNENNVDGLN ELNRGPRAKG TKNQKGNLDD SLEVKEQTGE SNVTEVGEAD
           NTCVVPDREQ YNKEDFPVDY ANAMFFIIKS YSEDDVHKSI KYNVWASTPN GNKKLAAAYQ
           EAQQKAGGCP IFLFFSVNAS GQFVGLAEMT GPVDFNTNVE YWQQDKWTGS FPLKWHIVKD
           VPNSLLKHIT LENNENKPVT NSRDTQEVKL EQGLKIVKIF KEHSSKTCIL DDFSFYEVRQ
           KTILEKKAKQ TQKQVSEEKV TDEKKESATA ESASKESPAA VQTSSDVKVA ENGSVAKPVT
           GDVVANGC*
49         MLAIFDKNVA KTPEALQGQE GGSVCALKDR FLPNHFSSVY PGAVTINLGS SGFIACSLEK
           QNPLLPRLFA VVDDMFCIFQ GHIENVPILK QQYGLTKTAT EVTIVIEAYR TLRDRGPYSA
           EQVVRDFQGK FGFMLYDCST QNVFLAGDVD GSVPLYWGTD AEGHLVVSDD VETVKKGCGK
           SFAPFPKGCF FTSSGGLRSY EHPSNELKPV PRVDSSGEVC GVTFKVDSEA KKEAMPRVGS
           VQNWSKQI*
50         MVNIPKTKNT YCKNKECKKH TLHKVTQYKK GKDSLAAQGK RRYDRKQSGY GGQTKPVFHK
           KAKTTKKIVL RLQCQSCKHF SQRPIKRCKH FEIGGDKKGK GTSLF*
51         MEKSNGLRVI LFPLPLQGCI NPMIQLAKIL HSRGFSITVI HTCFNAPKAS SHPLFTFLEI
           PDGLSETEKR TNNTKLLLTL LNRNCESPFR ECLSKLLQSA DSETGEEKQR ISCLIADSGW
           MFTQPIAQSL KLPILVLSVF TVSFFRCQFV LPKLRREVYL PLQDSEQEDL VQEFPPLRKK
           DIVRILDVET DILDPFLDKV LQMTKASSGL IFMSCEELDH DSVSQAREDF KIPIFGIGPS
           HSHFPATSSS LSTPDETCIP WLDKQEDKSV IYVSYGSIVT ISESDLIEIA WGLRNSDQPF
           LLVVRVGSVR GREWIETIPE EIMEKLNEKG KIVKWAPQQD VLKHRAIGGF LTHNGWSSTV
           ESVCEAVPMI CLPFRWDQML NARFVSDVWM VGINLEDRVE RNEIEGAIRR LLVEPEGEAI
           RERIEHLKEK VGRSFQQNGS AYQSLQNLID YISSF*
52         MADGEDIQPL VCDNGTGMVK AGFAGDDAPR AVFPSIVGRP RHTGVMVGMG QKDAYVGDEA
           QSKRGILTLK YPIEHGIVSN WDDMEKIWHH TFYNELRVAP EEHPVLLTEA PLNPKANREK
           MTQIMFETFN VPAMYVAIQA VLSLYASGRT TGIVLDSGDG VSHTVPIYEG YALPHAILRL
           DLAGRDLTDS LMKILTERGY MFTTTAEREI TRDIKEKLAY VALDYEQELE TAKSSSSVEK
           NYELPDGQVI TIGAERFRCP EVLFQPSLIG MEAPGIHETT YNSIMKCDVD IRKDLYGNIV
           LSGGSTMFPG IADRMSKEIT ALAPSSMKIK VVAPPERKYS VWIGGSILAS LSTFQQMWIS
           KSEYDESGPS IVHRKCF*
53         MEWEKWYLDA VLVPSALLMM FGYHIYLWYK VRTDPFCTIV GTNSRARRSW VAAIMKDNEK
           KNILAVQTLR NTIMGGTLMA TTCILLCAGL AAVLSSTYSI KKPLNDAVYG AHGDFTVALK
           YVTILTIFLF AFFSHSLSIR FINQVNILIN APQEPFSDDF GEIGSFVTPE YVSELLEKAF
           LLNTVGNRLF YMGLPLMLWI FGPVLVFLSS ALIIPVLYNL DFVFLLSNKE KGKVDCNGGC
           DDNFSP*
54         MGDARDNEAY EEELLDYEEE DEKVPDSGNK VNGEAVKKGY VGIHSSGFRD FLLKPELLRA
           IVDSGFEHPS EVQHECIPQA ILGMDVICQA KSGMGKTAVF VLSTLQQIEP SPGQVSALVL
           CETRELAYQI CNEFVRESTY LPDTKVSVFY GGVNIKIHKD LLKNECPHIV VGTPGRVLAL
           AREKDLSLKN VRHFILDECD KMLESLDMRR DVQEIFKMTP HDKQVMMFSA TLSKEIRPVC
           KKFMQDPMEI YVDDEAKLTL HGLVQHYIKL SEMEKTRKLN DLLDALDFNQ VVIFVKSVSR
           AAELNKLLVE CNFPSICIHS GMSQEERLTR YKSFKEGHKR ILVATDLVGR GIDIERVNIV
           INYDMPDSAD TYLHRVGRAG RFGTKGLAIT FVASASDSEV LNQVQERFEV DIKELPEQID
           TSTYSKCEIP YQLFV*
55         MATISNLANL PRATCVDSKS SSSSSVLPRS FVNFRALNAK LSSSQLSLRY NQRSIPSLSV
           RCSVSGGNGT AGKRTTLHDL YEKEGQSPWY DNLCRPVTDL LPLIARGVRG VTSNPAIFQK
           AISTSNAYND QFRTLVESGK DIESAYWELV VKDIQDACKL FEPIYDQTEG ADGYVSVEVS
           PRLADDTQGT VEAAKYLSKV VNRRNVYIKI PATAPCIPSI RDVIAAGISV NVTLIFSIAR
           YEAVIDAYLD GLEASGLDDL SRVTSVASFF VSRVDTLMDK MLEQIGTPEA LDLRGKAAVA
           QAALAYKLYQ QKFSGPRWEA LVKKGAKKQR LLWASTSVKN PAYSDTLYVA PLIGPDTVST
           MPDQALEAFA DHGIVKRTID ANVSEAEGIY SALEKLGIDW NKVGEQLEDE GVDSFKKSFE
           SLLGTLQDKA NTLKLASH*
56         MESPKNSLIP SFLYSSSSSP RSFLLDQVLN SNSNAAFEKS PSPAPRSSPT SMISRKNFLI
           ASPTEPGKGI EMYSPAFYAA CTFGGILSCG LTHMTVTPLD LVKCNMQIDP AKYKSISSGF
           GILLKEQGVK GFFRGWVPTL LGYSAQGACK FGFYEYFKKT YSDLAGPEYT AKYKTLIYLA
           GSASAEIIAD IALCPFEAVK VRVQTQPGFA RGMSDGFPKF IKSEGYGGLY KGLAPLWGRQ
           IPYTMMKFAS FETIVEMIYK YAIPNPKSEC SKGLQLGVSF AGGYVAGVFC AIVSHPADNL
           VSFLNNAKGA TVGDAVKKIG MVGLFTRGLP LRIVMIGTLT GAQWGLYDAF KVFVGLPTTG
           GVAPAPAIAA TEAKA*
57         MVEPANTVGL PVNPTPLLKD ELDIVIPTIR NLDFLEMWRP FLQPYHLIIV QDGDPSKKIH
           VPEGYDYELY NRNDINRILG PKASCISFKD SACRCFGYMV SKKKYIFTID DDCFVAKDPS
           GKAVNALEQH IKNLLCPSSP FFFNTLYDPY REGADFVRGY PFSLREGVST AVSHGLWLNI
           PDYDAPTQLV KPKERNTRYV DAVMTIPKGT LFPMCGMNLA FDRDLIGPAM YFGLMGDGQP
           IGRYDDMWAG WCIKVICDHL SLGVKTGLPY IYHSKASNPF VNLKKEYKGI FWQEEIIPFF
           QNAKLSKEAV TVQQCYIELS KMVKEKLSSL DPYFDKLADA MVTWIEAWDE LNPPAASGKA
           *
58         MSETNKNAFQ AGQAAGKAEE KSNVLLDKAK DAAAAAGASA QQAGKSISDA AVGGVNFVKD
           KTGLNK*
59         MASHIVGYPR MGPKRELKFA LESFWDGKST AEDLQKVSAD LRSSIWKQMS AAGTKFIPSN
           TFAHYDQVLD TTAMLGAVPP RYGYTGGEIG LDVYFSMARG NASVPAMEMT KWFDTNYHYI
           VPELGPEVNF SYASHKAVNE YKEAKALGVD TVPVLVGPVS YLLLSKAAKG VDKSFELLSL
           LPKILPIYKE VITELKAAGA TWIQLDEPVL VMDLEGQKLQ AFTGAYAELE STLSGLNVLV
           ETYFADIPAE AYKTLTSLKG VTAFGFDLVR GTKTLDLVKA GFPEGKYLFA GVVDGRNIWA
           NDFAASLSTL QALEGIVGKD KLVVSTSCSL LHTAVDLINE TKLDDEIKSW LAFAAQKVVE
           VNALAKALAG QKDEALFSAN AAALASRRSS PRVTNEGVQK AAAALKGSDH RRATNVSARL
           DAQQKKLNLP ILPTTTTGSF PQTVELRRVR REYKAKKVSE EDYVKAIKEE IKKVVDLQEE
           LDIDVLVHGE PERNDMVEYF GEQLSGFAFT ANGWVQSYGS RCVKPPVIYG DVSRPKAMTV
           FWSAMAQSMT SRPMKGMLTG PVTILNWSFV RNDQPRHETC YQIALAIKDE VEDLEKGGIG
           VIQIDEAALR EGLPLRKSEH AFYLDWAVHS FRITNCGVQD STQIHTHMCY SHFNDIIHSI
           IDMDADVITI ENSRSDEKLL SVFREGVKYG AGIGPGVYDI HSPRIPSSEE IADRVNKMLA
           VLEQNILWVN PDCGLKTRKY TEVKPALKNM VDAAKLIRSQ LASAK*
60         MEVLDRRDDE IRDSGNMDSI KSHYVTDSVS EERRSRELKD GDHPLRYKFS IWYTRRTPGV
           RNQSYEDNIK KMVEFSTVEG FWACYCHLAR SSLLPSPTDL HFFKDGIRPL WEDGANCNGG
           KWIIRFSKVV SARFWEDLLL ALVGDQLDDA DNICGAVLSV RFNEDIISVW NRNASDHQAV
           MGLRDSIKRH LKLPHAYVME YKPHDASLRD NSSYRNTWLR G*
61         GATCTCTGTTTCACAAG
62         GATCTGTGTTGTTAATT
63         GATCCTTGCTTGAGCTA
64         GATCCGTAACTCTTGAA
65         GATCCCTCTTTACAGTT
66         GATCCCGTGCTGCAGCT
67         GATCACTGGAATTTGAG
68         GATCGTTCCCTTGCTGC
69         GATCTTTTTTTTGTTCA
70         GATCCAATCTTAAAGGT
71         GATCATTTATGAGAAGC
72         GATCAATCAAGGAGAGT
73         GATCAGCATTTACAGTG
74         GATCCTCTTGATTAAAT
75         GATCTCAAAGGGTGAGT
76         GATCCGTTTCTTTGCCC
77         GATCAAAACACAATCCT
78         GATCGGTGGTGACAAGA
79         GATCGTTTCAACAAAAC
80         GATCAATCCTTGCATCC
81         GATCTTTGGGCCTGTGC
82         GATCTATTATCAATTTA
83         GATCATGGAATAGTGAA
84         GATCGGGACGTTGACTG
85         GATCATTCCGTTCTTCC
86         GATCCGAGTCAACTTTG
87         GATCCACACTCACATGT
88         GATCAAAACTATAAGGA
89         GATCTGAAAGAGAGAAG
90         GATCATCTTTTTTCTCC
91         GATCATGCATATTTGTT
92         GATCATTGAGAATCCAG
93         GATCATTCAAATCTTGT
94         GATCTCGACTTCTCTGC
95         GATCGTCTTCAAGGGCA
96         GATCACACCTCTGAGTC
97         GATCTACTATTATTAAG
98         GATCCGTTGATTTGCTC
99         GATCCAGACAACATGAA
100        GATCCCAATTCCTTGTT
101        GATCTCTCTGTCTCCCA
102        GATCTCTATTGGCAATA
103        GATCTCTACTCTCTTCT
104        GATCTGAGATAGAGACA
105        GATCCATTGAGATAATT
106        GATCTATTCCAGCGGAA
107        GATCCTAGAATATTTTT
108        GATCCTGTCATGGAATA
109        GATCGTTCGTGGTACTT
110        GATCGGCTTCTGCTCGA
111        GATCGGCATTACGACCC
112        GATCTCCTTTTGATTCT
113        GATCAAAATTCTCAACC
114        GATCTTGCCTTTTAAAC
115        GATCTTGTATAATGACA
116        GATCTTTATGGTGCTAG
117        GATCAACCCGATTCTTG
118        GATCAAGATTTTTTTTA
119        GATCACGCCTTTGTTTC
120        GATCAAGAATGTGTATG
121        GATCTGATTTTCTCAAC
122        GATCACACCGCAATGCT
123        GATCGACTCTTCTCGTT
124        GATCAATATGGTTTTGA
125        GATCGCGTCTGAATTGT
126        GATCTCTGTCATAGACT
127        GATCTCGGCATGTGTGT
128        GATCTTGGGTGCAATTT
129        GATCAACATGAATGAGG
130        GATCTTCTGCTAGGGAT
131        GATCCCGTATCTTGAAC
132        GATCCAGAAATTTCCAA
133        GATCGCGTCGTGTTACT
134        GATCTTAGCTTATGACT
135        GATCTATATTTTTCTAA
136        GATCCTTTTTGTAGTTT
137        GATCGACGATGTCATCT
138        GATCATTGAGTATGTTT
139        GATCAATCAATGGTTCA
140        GATCGACTCTCTTACTT
141        GATCTTTGTTTTTAAGA
142        GATCTTGGTTTTTAGAG
143        GATCTATTCGGTGAAAA
144        GATCACAGTGAACCCCG
145        GATCTTGTGGACATCTC
146        GATCGTTAATTCAATGC
147        GATCGAAGAAGCAGACC
148        GATCTGTGTGTCGTCCA
149        GATCTTCTGTGCTATGT
150        GATCTCTGGATTCATCG
151        GATCAGATGCAATTTGC
152        GATCCTCTCCTATGATG
153        GATCTTTGTAACGCACC
154        GATCTCATAAATGTTGG
155        GATCTCTGTGAGATTTG
156        GATCTGTAGCAAACACA
157        GATCATGCCTCTGTTCA
158        GATCTGGCGGAGCACCA
159        GATCTGACAAACGCAAC
160        GATCAATCAACCTTATG
161        GATCTGTAAAATACTAC
162        GATCATAAAGAGACAGA
163        GATCCGTGGTGTTAAGA
164        GATCCTTAACTTGAGGA
165        GATCGCAGTCGAGGAAT
166        GATCTTCTTGTTCGCAT
167        GATCATTCTTCTTTTGG
168        GATCTCGTCTTTGTTTT
169        GATCAGATAAAACACCT
170        GATCTGTAGCCAATGGA
171        GATCCAAATCCAAAGAG
172        GATCAGAGGAGAACGTG
173        GATCTAAGCTTAGCATC
174        GATCACAGTTTTGAAAT
175        GATCCAGAGGCGTTCAA
176        GATCTGATGAGCCAAAG
177        GATCAAAGCCATTGAAG
178        GATCCCGTGAGTGGATG
179        GATCCTGTTTTTGATTG
180        GATCTGAATAGCTGCGC
181        GATCATATACCAGTATT
182        GATCACATCTTTACCAG
183        GATCCTTCTAAGACTAA
184        GATCATTTCTGTTAGAA
185        GATCGTGGCCGTTGGAT
186        GATCATGCTCTCCAAAC
187        GATCCCAAACCGATGGT
188        GATCATTAGTCTCTCAT
189        GATCGGTGTGTTATACA
190        GATCTTGTCTCTGAGTA
191        GATCTTTCGCCTCTTCT
192        GATCTGCTGAAACTGAA
193        GATCTTTTTTTTTGTGT
194        GATCTCATCCATCTTCT
195        GATCTAAATCTGTGAAA
196        GATCAAAAAAAAAAAAA
197        GATCAAAACAACCTGCG
198        GATCAAAACAATGAGGG
199        GATCAAAACTGTTACAC
200        GATCAAAAGCTCTTACA
201        GATCAAAATTTGAGGGG
202        GATCAAAATTTGTAGTG
203        GATCAAACTGGTGAAGG
204        GATCAAACTTTGCTTGC
205        GATCAAATCATCTTCCA
206        GATCAAATGTCCCCACC
207        GATCAACGCAGCCAAGG
208        GATCAACTCTTTACATG
209        GATCAACTGTCAATTCA
210        GATCAACTTAAGCAAAA
211        GATCAACTTATAAGTGC
212        GATCAAGAAAGAAGAAG
213        GATCAAGAAGGTAACGC
214        GATCAAGCTGTCTTCAA
215        GATCAAGTTTACAGGAT
216        GATCAATAATTGTTTCT
217        GATCAATCTAGCGAACA
218        GATCAATTGATGGCGCA
219        GATCACAGATTCTGAAT
220        GATCACAGCAAGAGTGG
221        GATCACATGAGGAAGAT
222        GATCACCTTGTTGCTGC
223        GATCACGACCAAGTCAT
224        GATCACGGTTCTCGTCG
225        GATCACTGCTTTGGCTC
226        GATCACTTTCAGTGATA
227        GATCACTTTTAACTGTT
228        GATCACTTTTTTGTGGG
229        GATCAGAAGAGCAACGT
230        GATCAGAAGCAGTGCGT
231        GATCAGAAGGAACTGCA
232        GATCAGAATCATCAATA
233        GATCAGATGCAATGTGT
234        GATCAGATGGGATGGTA
235        GATCAGATTTTCTTGGG
236        GATCAGCGCCACTCTTC
237        GATCAGTTAGCTTCTCT
238        GATCAGTTGATGCTGGA
239        GATCATATGTTGCTGGA
240        GATCATCAAAACCATCC
241        GATCATCAAAATCAGTC
242        GATCATCACTATTTCAT
243        GATCATCCCCTGTCTGT
244        GATCATCCTTCTTTGCC
245        GATCATCGTTTCGTGTA
246        GATCATCTATTGGATGA
247        GATCATCTCACCTTTGT
248        GATCATCTGAAACCATC
249        GATCATCTGTGAATTTT
250        GATCATCTTTTGAATGT
251        GATCATGAAATGGTATG
252        GATCATGATTTCCTTCT
253        GATCATGCAATCAAGCA
254        GATCATGTGTTTGGTTT
255        GATCATTCTCCTCGCAA
256        GATCATTGGGAAATGAT
257        GATCATTGTTGTCTCAC
258        GATCATTTTATGTGATT
259        GATCATTTTCCAAACGC
260        GATCATTTTGATGCTTT
261        GATCATTTTTCTCTAAT
262        GATCATTTTTTTTTTTT
263        GATCCAAAAGACAAACA
264        GATCCAAAGAGTTGGAG
265        GATCCAAATCAACCTAA
266        GATCCAAGCTTTTAATG
267        GATCCAATAATACATAC
268        GATCCAATGGCACCAGC
269        GATCCAATTTGGTCAGA
270        GATCCACATGGAGGTAG
271        GATCCACCTGATGATGT
272        GATCCACGAGTTTCAGG
273        GATCCACGCGTGGGAGA
274        GATCCAGAAGCCGGAGT
275        GATCCAGAAGTTCTTGC
276        GATCCAGAGGTCTGGTT
277        GATCCAGCAGTGGTGTT
278        GATCCAGTTATTATGGA
279        GATCCAGTTTTTGTTTG
280        GATCCATGAACTGGACC
281        GATCCATTCACTGTTAA
282        GATCCATTCCGCAGTTC
283        GATCCATTTGTGATGAA
284        GATCCCAAACGACAAAA
285        GATCCCAAATTCCCAAT
286        GATCCCAGATTACGATT
287        GATCCCATTATCGCTAA
288        GATCCCATTTCTCACTG
289        GATCCCGATTGGAGTGC
290        GATCCCTCCGAAGCAGT
291        GATCCCTGCATACGGTG
292        GATCCGCTTCGCCTTCA
293        GATCCGGATATTTACAC
294        GATCCGTATCGTCGATT
295        GATCCGTCCTACTTGTC
296        GATCCGTCTTATTGCGT
297        GATCCTAACCATTATCC
298        GATCCTAGGAGAATACA
299        GATCCTATTCGTTGTTG
300        GATCCTCATCTTTCCTA
301        GATCCTCCTCGGACGAA
302        GATCCTCGGATGTGGCA
303        GATCCTGACGCCGTAGC
304        GATCCTGAGAATTTCTT
305        GATCCTTATCATCCGAG
306        GATCCTTATTTGGTGCC
307        GATCCTTCCGCAATGTT
308        GATCCTTCGTTAACGGC
309        GATCCTTGGATTTGGTC
310        GATCCTTGTGGCGACTG
311        GATCCTTTAGAACATTT
312        GATCCTTTCGACAAGAT
313        GATCCTTTCTTGGAAGA
314        GATCCTTTCTTTGGGGT
315        GATCCTTTTATCGAATC
316        GATCGAACCAAGTTTCA
317        GATCGAACCAGAGATAT
318        GATCGAATTCCTGGAAG
319        GATCGACAGTCTGGAGA
320        GATCGACGACTGGACTC
321        GATCGATGCCCTTGTGA
322        GATCGCCATTGAGAACA
323        GATCGCTGCAACGATGA
324        GATCGCTGCTCAGTTTG
325        GATCGGAAAGATTGTGG
326        GATCGGAATTCGTGATG
327        GATCGGAATTTCATGTG
328        GATCGGATTTTTTCTGA
329        GATCGGGAAGAGAGGAG
330        GATCGTATACTTCGTCC
331        GATCGTCAAGAAGAAGC
332        GATCGTCGTTCGATGAT
333        GATCGTGGTGTCCTCGC
334        GATCGTTAATTTTTTTT
335        GATCTAAACTTTTATGC
336        GATCTAAGTGGAATCTT
337        GATCTAATAGCAGAGTT
338        GATCTACCCGATTCTTT
339        GATCTACGCGTCCCTCT
340        GATCTACGTAAGTTTTC
341        GATCTACTCAACGAAGC
342        GATCTAGGCGCTTTTAC
343        GATCTATCCAGTTTGGT
344        GATCTATCTATTATTCC
345        GATCTATTCATAGAAGT
346        GATCTATTCTGTCCAAG
347        GATCTCAAAGTGACTGT
348        GATCTCAAGTTTCAATC
349        GATCTCAGATATTTTAA
350        GATCTCATACATTATGT
351        GATCTCATTATGCAATT
352        GATCTCCAGTTCGATAT
353        GATCTCCGTCCCAAGAA
354        GATCTCGAAAGCTATCA
355        GATCTCGGTGTTCCTTC
356        GATCTCTACAATTAGTG
357        GATCTCTCTAGCCTTTG
358        GATCTCTCTCGGCCTTG
359        GATCTCTCTTTATTGTC
360        GATCTCTTACACGTGCC
361        GATCTCTTTATGAAAGA
362        GATCTCTTTGTGACTAT
363        GATCTCTTTCTTTTTCT
364        GATCTGAAATCCGCCGT
365        GATCTGACTAATGTCAT
366        GATCTGAGTTTTATTTT
367        GATCTGATTGGTTTTGG
368        GATCTGATTGTGTTACC
369        GATCTGCACAAAGCATG
370        GATCTGCCAAAAGCACC
371        GATCTGCTGAAGAAAGT
372        GATCTGCTGGGAAAGTC
373        GATCTGGACCTTGTCCC
374        GATCTGGAGGTGCCTAA
375        GATCTGGTCTACTATAT
376        GATCTGGTTCGTTCCGT
377        GATCTGTTCTTCCAGCA
378        GATCTGTTTCATTAGAC
379        GATCTTAGTGACGATGA
380        GATCTTATTGTTGGTGA
381        GATCTTCAGTCTTGAGT
382        GATCTTCCCTTTTCTTT
383        GATCTTCTTGAGGAGGA
384        GATCTTCTTGGCATGCA
385        GATCTTGCAGCATTGGA
386        GATCTTGCTCGGCTTGC
387        GATCTTGTACCTTCTGA
388        GATCTTGTTGAAGGATG
389        GATCTTGTTTCTCGGTC
390        GATCTTTATCTTTATCT
391        GATCTTTCTTGTTTTGT
392        GATCTTTGTTGGTGTAA
393        GATCTTTTCTTGGATGA
394        GATCTTTTGGTCTTTTT
395        GATCTTTTTGGGGATAA
396        GATCTTTTTGTATGTTG
397        GATCTGAAAGAGAGAAG
398        GATCATCTTTTTTCTCC
399        GATCACTGGAATTTGAG
400        GATCGTTCCCTTGCTGC
401        GATCCAATCTTAAAGGT
402        GATCAATCAAGGAGAGT
403        GATCATGCATATTTGTT

Claims

1. A composition comprising at least one expression vector, wherein the at least one expression vector comprises a nucleic acid comprising: (a) at least one polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30 or a sequence complementary thereto; (b) at least one polynucleotide sequence comprising a conservative variation of a polynucleotide sequence of (a); (c) at least one polynucleotide encoding a polypeptide sequence selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60, or conservative variations thereof; (d) at least one polynucleotide sequence that hybridizes under stringent conditions to a polynucleotide sequence of (a) or (b); (e) at least one polynucleotide that is at least about 70% identical to a polynucleotide sequence of (a), or (b); or, (f) at least one polynucleotide sequence comprising at least 10 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30, or a sequence complementary thereto.

2. The composition of claim 1, wherein the at least one expression vector comprises a promoter operably linked to the nucleic acid comprising the polynucleotide of (a), (b), (c), (d) or (e).

3. The composition of claim 1, wherein the nucleic acid encodes a polypeptide.

4. The composition of claim 1, wherein the polypeptide comprises a polypeptide subsequence of SEQ ID NO: 31-SEQ ID NO: 60.

5. The composition of claim 1, wherein the nucleic acid encodes a sense or antisense RNA.

6. A cell comprising the at least one expression vector of claim 1.

7. The cell of claim 6, which cell expresses a polypeptide selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60, and conservative variations thereof.

8. An isolated or recombinant polypeptide comprising: (a) an amino acid sequence selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60, and conservative variants thereof; (b) an amino acid sequence encoded by a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 30, and conservative variations thereof; (c) an amino acid sequence encoded by a polynucleotide sequence that hybridizes under stringent conditions to a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 30; (d) an amino acid sequence encoded by a polynucleotide sequence that is at least about 70% identical to a polynucleotide selected from the group consisting of SEQ ID NO: 1 to SEQ ID NO: 30, or (e) a polypeptide comprising an amino acid subsequence of (a), (b), (c) or (d).

9. The isolated or recombinant polypeptide of claim 8, comprising a fusion protein.

10. The isolated or recombinant polypeptide of claim 8, comprising a peptide or polypeptide tag.

11. The isolated or recombinant polypeptide of claim 10, wherein the peptide or polypeptide tag comprises a reporter peptide or polypeptide.

12. The isolated or recombinant polypeptide of claim 10, wherein the peptide or polypeptide tag comprises an epitope.

13. The isolated or recombinant polypeptide of claim 10, wherein the peptide or polypeptide tag comprises a localization signal or sequence.

14. An array of polypeptides comprising two or more different polypeptides of claim 8.

15. An antibody specific for the isolated or recombinant polypeptide of claim 8.

16. The antibody of claim 15, wherein the antibody comprises a monoclonal antibody or polyclonal serum.

17. The antibody of claim 15, which antibody is specific for an epitope comprising a subsequence of a polypeptide selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60.

18. An isolated or recombinant polypeptide which specifically binds to the antibody of claim 15.

19. A cell comprising at least one exogenous nucleic acid, which cell expresses a polypeptide of claim 8.

20. The cell of claim 19, wherein the expressed polypeptide is encoded by the exogenous nucleic acid.

21. The cell of claim 19, wherein the exogenous nucleic acid comprises a promoter, which promoter regulates transcription of an endogenous nucleic acid encoding the polypeptide.

22. A labeled probe comprising a nucleic acid or polypeptide comprising: (a) a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30; conservative variants of any one of SEQ ID NO: 1-SEQ ID NO: 30; or, a subsequence of SEQ ID NO: 1-SEQ ID NO: 30; or a conservative variant thereof comprising at least 10 nucleotides; or a complementary sequence thereof; (b) a polypeptide or peptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 31-SEQ ID NO: 60; a conservative variant of any one of SEQ ID NO: 31-SEQ ID NO: 60, or, a subsequence of one or more of SEQ ID NO: 31-SEQ ID NO: 60, or one or more conservative variants thereof, comprising at least six amino acids; or, (c) an antibody specific for a polypeptide or peptide sequence of (b).

23. The labeled probe of claim 22, wherein the polynucleotide sequence comprises a subsequence of SEQ ID NO: 1-SEQ ID NO: 30, comprising at least 12 nucleotides.

24. The labeled probe of claim 22, wherein the polynucleotide sequence comprises a subsequence of SEQ ID NO: 1-SEQ ID NO: 30, comprising at least 14 nucleotides.

25. The labeled probe of claim 22, wherein the polynucleotide sequence comprises a subsequence of SEQ ID NO: 1-SEQ ID NO: 30, comprising at least 16 nucleotides.

26. The labeled probe of claim 22, wherein the polynucleotide sequence comprises subsequence of SEQ ID NO: 1-SEQ ID NO: 30 comprising at least 17 nucleotides.

27. The labeled probe of claim 22, comprising an antigenic peptide.

28. The labeled probe of claim 22, comprising a fusion protein.

29. The labeled probe of claim 22, comprising an epitope tag.

30. The labeled probe of claim 22, comprising an isotopic, fluorescent, fluorogenic or colorimetric label.

31. The labeled probe of claim 22, comprising a DNA or RNA molecule.

32. A labeled probe of claim 22, comprising a cDNA, an amplification product, a transcript, a restriction fragment, or an oligonucleotide.

33. A labeled probe of claim 22, comprising an oligonucleotide consisting of a polynucleotide sequence selected from a subsequence of SEQ ID NO: 61 to SEQ ID NO: 403, or a conservative variation thereof.

34. A marker set for predicting at least one growth trait of a plant cell, the marker set comprising a plurality of members, which members comprise: (a) one or more polynucleotides sequences selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30 or SEQ ID NO: 61-SEQ ID NO: 403; a conservative variant of any one of SEQ ID NO: 1-SEQ ID NO: 30 or SEQ ID NO: 61-SEQ ID NO: 403; a subsequence of SEQ ID NO: 1-SEQ ID NO: 30, SEQ ID NO: 61-SEQ ID NO: 403, or a conservative variant thereof comprising at least 10 nucleotides; and, a complementary sequence thereof; (b) one or more polypeptides or peptides comprising an amino acid selected from the group consisting of: SEQ ID NO: 31 to SEQ ID NO: 60; a conservative variant of any one of SEQ ID NO: 31 to SEQ ID NO: 60; or a subsequence of SEQ ID NO: 31-SEQ ID NO: 60 or a conservative variant thereof comprising at least six amino acids; and/or, (c) one or more antibodies specific for a polypeptide or peptide sequence of (b).

35. The marker set of claim 34, wherein the nucleic acids comprise oligonucleotides, expression products, or amplification products.

36. The marker set of claim 35, wherein the oligonucleotides are synthetic oligonucleotides.

37. The marker set of claim 34, comprising a plurality of labeled nucleic acid probes.

38. The marker set of claim 34, comprising a plurality of polypeptides or peptides.

39. The marker set of claim 34, comprising a plurality of antibodies.

40. The marker set of claim 34, comprising a plurality of members, which members include nucleic acids and polypeptides.

41. The marker set of claim 34, wherein the nucleic acids or polypeptides are logically or physically arrayed.

42. The marker set of claim 34, wherein the nucleic acids or polypeptides are physically arrayed in a solid phase or liquid phase array.

43. The marker set of claim 41, wherein the array comprises a bead array.

44. The marker set of claim 34, wherein each member of the marker set comprises at least 10 contiguous nucleotides from at least one of SEQ ID NO: 1-SEQ ID NO: 30.

45. The marker set of claim 34, comprising a plurality of members that together comprise a plurality of sequences or subsequences selected from a plurality of nucleic acids represented by SEQ ID NO: 61-SEQ ID NO: 403.

46. The marker set of claim 34, comprising a majority of members that together comprise a majority of sequences or subsequences selected from a majority of nucleic acids represented by SEQ ID NO: 61-SEQ ID NO: 403.

47. The marker set of claim 34, wherein each member of the marker set comprises at least 10 contiguous nucleotides from at least one of SEQ ID NO: 61-SEQ ID NO: 403.

48. The marker set of claim 34, wherein each member of the marker set comprises at least six contiguous amino acids from at least one of SEQ ID NO: 31-SEQ ID NO: 60.

49. The marker set of claim 34, comprising at least one antibody specific for each of SEQ ID NO: 31-SEQ ID NO: 60, or a subsequence thereof.

50. The marker set of claim 34, wherein a plant growth trait is predicted by hybridizing the nucleic acids of the marker set to a DNA or RNA sample from a cell or tissue, and detecting at least one polymorphic polynucleotide or differentially expressed expression product.

51. An array comprising the marker set of claim 34.

52. A method for modulating a plant growth trait, the method comprising: modulating expression or activity of at least one polypeptide encoded by a nucleic acid comprising: (a) at least one polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30 or a sequence complementary thereto; (b) at least one polynucleotide sequence comprising a conservative variation of a polynucleotide sequence of (a); (c) at least one polynucleotide encoding a polypeptide sequence selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60, or conservative variations thereof; (d) at least one polynucleotide sequence that hybridizes under stringent conditions to a polynucleotide sequence of (a) or (b); (e) at least one polynucleotide that is at least about 70% identical to a polynucleotide sequence of (a), or (b); or, (f) at least one polynucleotide sequence comprising at least 10 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30, or a sequence complementary thereto.

53. The method of claim 52, comprising modulating expression or activity of at least one polypeptide contributing to a plant growth trait.

54. The method of claim 52, comprising modulating a plant growth trait in a flowering plant.

55. The method of claim 52, comprising modulating a plant growth trait in a member of the family Brassicaceae.

56. The method of claim 52, comprising modulating a plant growth trait in a plant selected from the group consisting of Arabidopsis, Brassica, Zea, Oryza, Triticum, Hordeum, Lolium, Sorghum, Glycine, Medicago, Helianthus, Lactuca, Beta, Vitis, Solanum, Lycopersicon, Capsicum, Gossypium, Hevea, Linum, Prunus, Citrus, Populus, Pinus, Quercus, and Saccharomyces.

57. The method of claim 52, comprising modulating expression by expressing an exogenous nucleic acid comprising a polynucleotide sequence selected from SEQ ID NO: 1 to SEQ ID NO: 30.

58. The method of claim 57, comprising modulating expression by inducing or suppressing expression of an endogenous nucleic acid.

59. The method of claim 58, wherein the endogenous nucleic acid encodes a polypeptide selected from among SEQ ID NO: 31-SEQ ID NO: 60, or homologues thereof.

60. The method of claim 57, comprising introducing the exogenous nucleic acid comprising at least one promoter, which promoter regulates expression of an endogenous nucleic acid modulating a plant growth trait.

61. The method of claim 57, further comprising detecting altered expression or activity of an expression product encoded by a nucleic acid comprising a polynucleotide sequence selected from SEQ ID NO: 1-SEQ ID NO: 30, or conservative variants thereof.

62. The method of claim 61, comprising detecting altered expression or activity in a high throughput assay.

63. The method of claim 52, wherein expression is modulated in response to an environmental factor, a chemical or biological agent, a pathogen, a bacteria, a virus, a fungus, or an insect.

64. The method of claim 63, comprising detecting altered expression or activity in response to the presence of a fertilizer, or an herbicide.

65. The method of claim 63, wherein a plurality of expression products are detected.

66. The method of claim 65, wherein the plurality of expression products are detected in an array.

67. The method of claim 66, wherein the array comprises a bead array.

68. The method of claim 63, wherein a data record comprising the altered expression or activity is recorded in a database.

69. The method of claim 68, wherein the database comprises a plurality of character strings recorded on a computer or in a computer readable medium.

70. A method for detecting genes for a plant growth trait, the method comprising: (i) providing a subject cell or tissue sample of nucleic acids; (ii) detecting at least one polymorphic nucleic acid or at least one expression product corresponding to a polynucleotide sequence, comprising; (a) at least one polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30 or a sequence complementary thereto; (b) at least one polynucleotide sequence comprising a conservative variation of a polynucleotide sequence of (a); (c) at least one polynucleotide encoding a polypeptide sequence selected from the group consisting of SEQ ID NO: 31-SEQ ID NO: 60, or conservative variations thereof; (d) at least one polynucleotide sequence that hybridizes under stringent conditions to a polynucleotide sequence of (a) or (b); (e) at least one polynucleotide that is about 70% identical to a polynucleotide sequence of (a), or (b); or, (f) at least one polynucleotide sequence comprising at least 10 contiguous nucleotides of a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1-SEQ ID NO: 30, or a sequence complementary thereto.

71. The method of claim 70, wherein the expression product comprises an RNA.

72. The method of claim 70, wherein the detecting step comprises qualitative detection.

73. The method of claim 70, wherein the detecting step comprises quantitative detection.