Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution
Large-scale DNA editing of retrotransposons accelerates mammalian genome evolution
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DOI：
10.1038/ncomms1525
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发表时间：
2011-11-01
影响因子：
16.6
通讯作者：
Levanon, Erez Y.
中科院分区：
文献类型：
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作者：
Carmi, Shai;Church, George M.;Levanon, Erez Y.
反转录转座子在基因组进化中起着重要作用，包括新基因和启动子的形成以及基因网络的重新布线。然而，目前尚不清楚这些功能是如何从数量相对有限的源序列中产生的。在这里，我们展示了DNA编辑，一种抗病毒机制，通过大规模修饰它们的反转录转座子序列来加速哺乳动物基因组的进化。我们发现许多反转录转座子对含有长簇G-to-A突变，不能归因于随机突变。我们在不同的哺乳动物基因组和反转录转座子家族中发现的这些簇是APOBEC3活性的标志，APOBEC3是一种具有胞苷脱胺功能的强效抗逆转录病毒蛋白家族。由于DNA编辑同时产生大量突变，每个受影响的元件都从一个独特的起点开始其进化轨迹，从而增加了开发新功能的可能性。因此，我们的发现提示了逆转录转座子驯化的潜在机制。
Retrotransposons had an important role in genome evolution, including the formation of new genes and promoters and the rewiring of gene networks. However, it is unclear how such a repertoire of functions emerged from a relatively limited number of source sequences. Here we show that DNA editing, an antiviral mechanism, accelerated the evolution of mammalian genomes by large-scale modification of their retrotransposon sequences. We find numerous pairs of retrotransposons containing long clusters of G-to-A mutations that cannot be attributed to random mutagenesis. These clusters, which we find across different mammalian genomes and retrotransposon families, are the hallmark of APOBEC3 activity, a potent antiretroviral protein family with cytidine deamination function. As DNA editing simultaneously generates a large number of mutations, each affected element begins its evolutionary trajectory from a unique starting point, thereby increasing the probability of developing a novel function. Our findings thus suggest a potential mechanism for retrotransposon domestication.