van de Lagemaat Louie N, Gagnier Liane, Medstrand Patrik, Mager Dixie L
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
Genome Res. 2005 Sep;15(9):1243-9. doi: 10.1101/gr.3910705.
Insertion of transposable elements is a major cause of genomic expansion in eukaryotes. Less is understood, however, about mechanisms underlying contraction of genomes. In this study, we show that retroelements can, in rare cases, be precisely deleted from primate genomes, most likely via recombination between 10- to 20-bp target site duplications (TSDs) flanking the retroelement. The deleted loci are indistinguishable from pre-integration sites, effectively reversing the insertion. Through human-chimpanzee-Rhesus monkey genomic comparisons, we estimate that 0.5%-1% of apparent retroelement "insertions" distinguishing humans and chimpanzees actually represent deletions. Furthermore, we demonstrate that 19% of genomic deletions of 200-500 bp that have occurred since the human-chimpanzee divergence are associated with flanking identical repeats of at least 10 bp. A large number of deletions internal to Alu elements were also found flanked by homologies. These results suggest that illegitimate recombination between short direct repeats has played a significant role in human genome evolution. Moreover, this study lends perspective to the view that insertions of retroelements represent unidirectional genetic events.
转座元件的插入是真核生物基因组扩张的主要原因。然而,对于基因组收缩背后的机制了解较少。在本研究中,我们表明,在极少数情况下,逆转录元件可以从灵长类动物基因组中精确删除,最有可能是通过逆转录元件两侧10至20个碱基对的靶位点重复序列(TSD)之间的重组。删除的位点与整合前的位点无法区分,有效地逆转了插入。通过人类-黑猩猩-恒河猴基因组比较,我们估计,区分人类和黑猩猩的明显逆转录元件“插入”中,有0.5%-1%实际上代表删除。此外,我们证明,自人类与黑猩猩分化以来发生的200-500碱基对的基因组删除中,19%与至少10个碱基对的侧翼相同重复序列有关。在Alu元件内部也发现大量缺失两侧存在同源性。这些结果表明,短直向重复序列之间的异常重组在人类基因组进化中发挥了重要作用。此外,本研究为逆转录元件插入代表单向遗传事件的观点提供了新视角。