Selection Against Deleterious LINE-1-Containing Loci in the Human Lineage
TLDR
It is concluded that most FL L1s were deleterious and thus subject to purifying selection and that genetic damage produced by both L1 retrotransposition and ectopic recombination between L1 elements could provide the basis for their negative selection.Abstract:
We compared sex chromosomal and autosomal regions of similar GC contents and found that the human Y chromosome contains nine times as many full-length (FL) ancestral LINE-1 (L1) elements per megabase as do autosomes and that the X chromosome contains three times as many. In addition, both sex chromosomes contain a ca. twofold excess of elements that are >500 bp but not long enough to be capable of autonomous replication. In contrast, the autosomes are not deficient in short (<500 bp) L1 elements or SINE elements relative to the sex chromosomes. Since neither the Y nor the X chromosome, when present in males, can be cleared of deleterious genetic loci by recombination, we conclude that most FL L1s were deleterious and thus subject to purifying selection. Comparison between nonrecombining and recombining regions of autosome 21 supported this conclusion. We were able to identify a subset of loci in the human DNA database that once contained active L1 elements, and we found by using the polymerase chain reaction that 72% of them no longer contain L1 elements in a representative of each of eight different ethnic groups. Genetic damage produced by both L1 retrotransposition and ectopic (nonallelic) recombination between L1 elements could provide the basis for their negative selection.read more
Citations
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Journal ArticleDOI
Natural mutagenesis of human genomes by endogenous retrotransposons.
Rebecca C. Iskow,Michael T. McCabe,Michael T. McCabe,Ryan E. Mills,Spencer Torene,W. Stephen Pittard,Andrew F. Neuwald,Erwin G. Van Meir,Erwin G. Van Meir,Paula M. Vertino,Paula M. Vertino,Scott E. Devine +11 more
TL;DR: The data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases.
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Dynamic interactions between transposable elements and their hosts
Henry L. Levin,John V. Moran +1 more
TL;DR: Recent findings about how, where and when transposable elements insert in diverse organisms are discussed.
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Mobile elements and mammalian genome evolution
TL;DR: The combination of whole-genome sequences and the development of innovative new assays to test the function of mobile elements have increased understanding of how these elements mobilize and how their insertion impacts genome diversity and human disease.
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Roles for retrotransposon insertions in human disease
TL;DR: An overview of LINE-1 biology is provided followed by highlights from new reports of Line-1-mediated genetic disease in humans, which provide a wealth of insight and the foundation for valuable tools to study these genomic parasites.
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Human L1 element target-primed reverse transcription in vitro
TL;DR: The initial stages of L1 element transposition in vitro is reconstituted and evidence for specific positioning of the L1 RNA with the ORF2 protein is found, probably mediated in part by the polyadenosine portion of L 1 RNA.
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