Long-term reinfection of the human genome by endogenous retroviruses
Long-term reinfection of the human genome by endogenous retroviruses
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DOI：
10.1073/pnas.0307800101
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发表时间：
2004-04-06
影响因子：
11.1
通讯作者：
Tristem, M
中科院分区：
文献类型：
--
作者：
Belshaw, R;Pereira, V;Tristem, M
内源性逆转录病毒（ERV）家族是通过生殖系感染和在宿主基因组内增殖的过程从其外源性对应物衍生而来的。人类和小鼠基因组中的几个家族现在由数百个元素组成，尽管已经提出了几个候选者，但这种增殖背后的机制仍然不确定。为了研究这一机制，我们重建了人类ERV家族HERV-K（HML 2）进化过程中非同义变化与同义变化的比例以及终止密码子的获得。我们发现，所有的基因，包括env基因，这是必要的，只有在细胞之间的运动，一直在不断的净化选择。这一发现有力地表明，该家族的增殖几乎完全是由于生殖系再感染，而不是顺式逆转录转座或反式互补，并且在过去的3000万年中，内源性逆转录病毒的感染池一直存在于灵长类谱系中。由于该库中的许多元件都是未固定的，因此HERV-K（HML 2）家族目前可能仍然包含感染性元件，尽管它们在人类基因组序列中明显缺失。对其他8个HERV家族的env基因的分析表明，再感染可能是内源性逆转录病毒在其宿主中增殖的最常见机制。
Endogenous retrovirus (ERV) families are derived from their exogenous counterparts by means of a process of germ-line infection and proliferation within the host genome. Several families in the human and mouse genomes now consist of many hundreds of elements and, although several candidates have been proposed, the mechanism behind this proliferation has remained uncertain. To investigate this mechanism, we reconstructed the ratio of nonsynonymous to synonymous changes and the acquisition of stop codons during the evolution of the human ERV family HERV-K(HML2). We show that all genes, including the env gene, which is necessary only for movement between cells, have been under continuous purifying selection. This finding strongly suggests that the proliferation of this family has been almost entirely due to germ-line reinfection, rather than retrotransposition in cis or complementation in trans, and that an infectious pool of endogenous retroviruses has persisted within the primate lineage throughout the past 30 million years. Because many elements within this pool would have been unfixed, it is possible that the HERV-K(HML2) family still contains infectious elements at present, despite their apparent absence in the human genome sequence. Analysis of the env gene of eight other HERV families indicated that reinfection is likely to be the most common mechanism by which endogenous retroviruses proliferate in their hosts.