The impact of retrotransposons on human genome evolution

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Abstract
LINE-1 (L1), Alu and SVA elements belong to the non-long terminal repeat retrotransposon class of transposable elements, and they account for approximately one-third of the human genome. L1, Alu and SVA elements are the only transposable elements that have unequivocally been shown to be currently active in humans, as shown by de novo insertions that are responsible for genetic disorders. The expansion of L1, Alu and SVA elements is characterized by the dispersal in a series of subfamilies of elements of different evolutionary age that share common nucleotide substitutions. This expansion follows the 'master gene' model of amplification. The evolutionary impact of L1, Alu and SVA elements on the human genome is substantial and extremely diverse. L1, Alu and SVA elements generate instability at a local genomic scale owing to retrotransposon insertion (for example, insertion mutagenesis and DNA repair) and the effect of L1-encoded proteins (for example, the generation of DNA double-strand breaks). These elements also affect genome sequences across longer timescales through, for example, the seeding of microsatellites and gene conversion. L1, Alu and SVA elements also generate genomic rearrangements such as deletions, duplications and inversions, and therefore create structural variation in the genome through insertion-mediated deletions, ectopic recombination and the transduction of flanking sequences. L1, Alu and SVA elements have fostered genetic innovation during human and primate evolution through transduction-mediated gene formation, gene retrotransposition and exonization. L1, Alu and SVA elements also substantially shape human evolution at the RNA level by modulating the expression of nearby genes, RNA editing and epigenetic regulation.