LINE-1 is a retrotransposon with copies at about 100,000 positions per mammalian genome. Insertional mutagenesis caused by LINE-1 transposition has been shown to cause genetic disease in humans and mice. Most LINE-1 insertions are truncated, or otherwise defective, and incapable of further transposition. New insertions are derived from some number of active LINE- 1 parental loci, at least some of which are widely distributed in the population. The factors that control the activity of these loci are unknown, but evidence is presented that genetic drift of these loci to a high allele frequency in the population is an important part of the overall dynamics of LINE-1 transposition. This proposal exploits two experimental systems to study the spread of LINE-1 sequences within natural populations. Both involve exchanges between the closely related mouse Species: Mus spretus and Mus musculus domesticus. These two species can interbreed to produce fertile female and infertile male offspring in captivity, but apparently interbreed very rarely in nature. As a result of the nearly complete reproductive isolation of the two species, their LINE- 1 elements have distinct sequences. However, evidence is presented that some DNA exchanges between the species in nature: enough to generate a detectable number of LINE-1 sequences that had originated in one species and are now present in the other. It is proposed to study the spread of inactive LINE-1 elements after they cross the species barrier as a means of measuring the rate of gene migration in wild populations. The rate of gene migration is a fundamental biological issue in itself; and it is demonstrated that the use of LINE-1 sequences in this way provides the fundamental advantage of defining how much time passed during the observed migration. Secondly, it is shown that active LINE-1 loci have occasionally crossed the species barrier, and then proceeded to amplify a substantial LINE-1 subfamily in the new species. It is proposed to study the extent and duration of amplification of invading LINE-1 subfamilies to gain clues about the constraints operating on LINE-1 transposition.
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