Belshaw Robert, Pereira Vini, Katzourakis Aris, Talbot Gillian, Paces Jan, Burt Austin, Tristem Michael
Department of Biological Sciences, Imperial College at Silwood Park, Ascot, Berks SL5 7PY, United Kingdom.
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4894-9. doi: 10.1073/pnas.0307800101. Epub 2004 Mar 25.
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.
内源性逆转录病毒（ERV）家族源自其外源性对应物，是通过种系感染以及在宿主基因组内增殖的过程产生的。人类和小鼠基因组中的几个家族现在由数百个元件组成，尽管已经提出了几个候选机制，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（HML2）进化过程中非同义突变与同义突变的比率以及终止密码子的获得情况。我们发现，所有基因，包括仅在细胞间移动时必需的env基因，都一直处于持续的纯化选择之下。这一发现强烈表明，这个家族的增殖几乎完全是由于种系再感染，而不是顺式逆转录转座或反式互补，并且在过去3000万年中，内源性逆转录病毒的一个感染库一直在灵长类谱系中持续存在。由于这个库中的许多元件可能尚未固定，因此尽管在人类基因组序列中明显不存在，但HERV-K（HML2）家族目前仍可能包含感染性元件。对其他八个HERV家族的env基因分析表明，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。
