Boissinot Stephane, Davis Jerel, Entezam Ali, Petrov Dimitri, Furano Anthony V
Section on Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, Building 8, Room 203, 8 Center Drive, MSC O830, Bethesda, MD 20892-0830, USA.
Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9590-4. doi: 10.1073/pnas.0603334103. Epub 2006 Jun 9.
The self-replicating LINE-1 (L1) retrotransposon family is the dominant retrotransposon family in mammals and has generated 30-40% of their genomes. Active L1 families are present in modern mammals but the important question of whether these currently active families affect the genetic fitness of their hosts has not been addressed. This issue is of particular relevance to humans as Homo sapiens contains the active L1 Ta1 subfamily of the human specific Ta (L1Pa1) L1 family. Although DNA insertions generated by the Ta1 subfamily can cause genetic defects in current humans, these are relatively rare, and it is not known whether Ta1-generated inserts or any other property of Ta1 elements have been sufficiently deleterious to reduce the fitness of humans. Here we show that full-length (FL) Ta1 elements, but not the truncated Ta1 elements or SINE (Alu) insertions generated by Ta1 activity, were subject to negative selection. Thus, one or more properties unique to FL L1 elements constitute a genetic burden for modern humans. We also found that the FL Ta1 elements became more deleterious as the expansion of Ta1 has proceeded. Because this expansion is ongoing, the Ta1 subfamily almost certainly continues to decrease the fitness of modern humans.
自我复制的LINE-1（L1）逆转录转座子家族是哺乳动物中占主导地位的逆转录转座子家族，其在哺乳动物基因组中所占比例达30%-40%。现代哺乳动物中存在活跃的L1家族，但这些当前活跃的家族是否会影响其宿主的遗传适应性这一重要问题尚未得到解决。这个问题对人类尤为重要，因为智人包含人类特有的Ta（L1Pa1）L1家族的活跃L1 Ta1亚家族。虽然Ta1亚家族产生的DNA插入可能会在当代人类中导致遗传缺陷，但这种情况相对罕见，而且尚不清楚Ta1产生的插入片段或Ta1元件的任何其他特性是否已造成足够大的危害以降低人类的适应性。在这里，我们表明全长（FL）Ta1元件，而非由Ta1活性产生的截短的Ta1元件或短散在核元件（Alu）插入，受到了负选择。因此，FL L1元件特有的一种或多种特性构成了现代人类的遗传负担。我们还发现，随着Ta1的扩张，FL Ta1元件变得更具危害性。由于这种扩张仍在进行，Ta1亚家族几乎肯定会继续降低现代人类的适应性。
