On the Estimation of the Insertion Time of LTR Retrotransposable Elements
On the Estimation of the Insertion Time of LTR Retrotransposable Elements
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DOI：
10.1093/molbev/msp295
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发表时间：
2010-04-01
影响因子：
10.7
通讯作者：
Innan, Hideki
中科院分区：
文献类型：
--
作者：
Kijima, T. E.;Innan, Hideki
有人提出，长末端重复序列（LTR）反转录转座子的插入时间可以通过两个LTR在两端的差异来估计，因为它们的序列在插入事件中是相同的。该方法基于两个LTR独立地积累点突变的假设;因此，分歧反映了自插入事件以来的时间。然而，如果基因转换发生在LTR之间，则核苷酸差异将比假设点突变独立累积的预期小得多。为了检验这一假设，我们通过将比较基因组方法应用于灵长类动物（人类和恒河猴）和啮齿类动物（小鼠和大鼠）来研究LTR之间的基因转换程度。我们发现，基因转换在灵长类和啮齿类LTR的分子进化中起着重要作用，但程度不同。在啮齿类动物中，大多数LTR都经历了广泛的基因转换，从而降低了分歧，因此基于分歧的方法导致严重低估了插入时间。在灵长类动物中，这种效应仅限于一小部分LTR。最可能的解释差异涉及相互作用序列的最小长度（最小有效加工段[MEPS]）的基因座间基因转换。人类MEPS的经验估计为300-500 bp，这超过了大多数分析的LTR的长度。相比之下，小鼠的MEPS应该小得多。因此，MEPS可能是决定LTR对基因转换易感性的重要因素，尽管还有许多其他因素参与其中。它的结论是，分歧的方法来估计插入时间应特别谨慎，因为至少有一些LTR进行基因转换。
It has been proposed that the insertion time of a long terminal repeat (LTR) retrotransposon can be estimated by the divergence between the two LTRs at the both ends because their sequences were identical at the insertion event. This method is based on the assumption that the two LTRs accumulate point mutations independently; therefore, the divergence reflects the time since the insertion event. However, if gene conversion occurs between LTRs, the nucleotide divergence will be much smaller than expected with the assumption of the independent accumulation of point mutations. To examine this assumption, we investigated the extent of gene conversion between LTRs by applying a comparative genomic approach to primates (humans and rhesus macaques) and rodents (mice and rats). We found that gene conversion plays a significant role in the molecular evolution of LTRs in primates and rodents, but the extent is quite different. In rodents, most LTRs are subject to extensive gene conversion that reduces the divergence, so that the divergence-based method results in a serious underestimation of the insertion time. In primates, this effect is limited to a small proportion of LTRs. The most likely explanation of the difference involves the minimum length of the interacting sequence (minimal efficient processing segment [MEPS]) for interlocus gene conversion. An empirical estimate of MEPS in human is 300-500 bp, which exceeds the length of most of the analyzed LTRs. In contrast, MEPS for mice should be much smaller. Thus, MEPS can be an important factor to determine the susceptibility of LTRs to gene conversion, although there are many other factors involved. It is concluded that the divergence method to estimate the insertion time should be applied with special caution because at least some LTRs undergo gene conversion.