title: The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.
abstract: Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Sandra R
authors.initials: SR
authors.lastname: Richardson
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Aurélien J
authors.initials: AJ
authors.lastname: Doucet
authors.affiliation: Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: Huira C
authors.initials: HC
authors.lastname: Kopera
authors.affiliation: Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109.
authors.forename: John B
authors.initials: JB
authors.lastname: Moldovan
authors.affiliation: Department of Human DNA Variability, GENYO (Pfizer-University of Granada & Andalusian Regional Government Genomics & Oncology Center), 18016 Granada, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Garcia-Perez
authors.affiliation: Department of Human Genetics; Cellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: John V
authors.initials: JV
authors.lastname: Moran
mesh_terms: D000818:Animals; D030342:Genetic Diseases, Inborn; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D008322:Mammals; D011995:Recombination, Genetic; D020086:Short Interspersed Nucleotide Elements