Research Project
6504803
DESCRIPTION (provided by applicant): Retroposons, RNA-mediated transposable elements, contribute to genomic variability among mammals. Mammalian genomes may reach to more than one million genomic integrations of short and long interspersed DNA elements (SINEs and LINEs) scattered throughout the chromosomes. The mechanism of retropositional activity and regulation of these "genomic parasites," as well as their impact on the genome and role in evolution, are not well understood. It is therefore imperative to address this subject as these elements have the potential to wreak havoc on the genome as evidenced by recent somatic and germ-line integrations into human genes yielding detrimental results, and by providing a source for disadvantageous unequal homologous recombination. The guinea pig genome contains a paucity of elements from three known rodent SINE families (i.e., only as many as 200 copies), warranting further investigation to help ascertain the critical steps of retroposition. It would seem unlikely that "master genes" for every SINE family have been weak. One preferred hypothesis is that LINEs provide the retropositional machinery for the non-autonomous SINEs, including the enzymes for reverse transcriptase and an endonuclease for genomic integration. It is therefore possible that the guinea pig (and other Hystricognath rodents) have not had an active LINE available for SINE dispersal. An alternative hypothesis is that additional general functioning trans-acting factors either are required for retroposon dispersal but are lacking, or are involved in repression of retroposition. The goal of this study is to elucidate retroposition regulatory mechanisms. This investigation involves: 1) a detailed analysis of the guinea pig genome to verify the presence or absence of any prolific SINE family; 2) an analysis of the level of LINE amplification, and the presence or absence of current LINE activity in the guinea pig; 3) an analysis of known highly active mouse and human LINEs for retroposition competency in guinea pig cells; and 4) an analysis to determine if prolific mouse SINEs utilize a presumptive intermediate step associated with LINEs.
