Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution
Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: Implications for human and viral evolution
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DOI：
10.1073/pnas.0307885100
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发表时间：
2004-02-10
影响因子：
11.1
通讯作者：
Coffin, JM
中科院分区：
文献类型：
--
作者：
Hughes, JF;Coffin, JM
人类内源性逆转录病毒(HERV)是人类基因组遗传多样性的潜在来源。尽管随着时间的推移，这些元件中的许多已经被有害突变的积累或内部重组而失活，导致Sone-LTR的形成，但HERV-K家族的几个成员已经被发现，它们几乎保持完整，可能代表最近的整合事件。为了确定HERV-K元件是否导致了人类基因组最近的变化，我们对存在于人类群体中的HERV-K多态水平进行了研究。通过使用高分辨率非印迹技术，我们分析了18个个体的13个人类特异性HERV-K元件。我们发现在这些基因座中有五个形成了单独的LTRs。这些结果使得能够估计人类基因组中HERV solo-LTR的形成，并表明这些事件发生的频率比在近交系小鼠中描述的要频繁得多。对一个前病毒的详细序列分析表明，在近代历史上，SOLO-LTR的形成至少发生了三次。在这两个个体中也存在一个未被占据的预整合部位，这表明尽管这种前病毒的年龄估计约为120万年，但它在人类群体中还没有成为固定的。
Human endogenous retroviruses (HERVs) are a potential source of genetic diversity in the human genome. Although many of these elements have been inactivated over time by the accumulation of deleterious mutations or internal recombination leading to solo-LTR formation, several members of the HERV-K family have been identified that remain nearly intact and probably represent recent integration events. To determine whether HERV-K elements have caused recent changes in the human genome, we have undertaken a study of the level of HERV-K polymorphism that exists in the human population. By using a high-resolution unblotting technique, we analyzed 13 human-specific HERV-K elements in 18 individuals. We found that solo LTRs have formed at five of these loci. These results enable the estimation of HERV solo-LTR formation in the human genome and indicate that these events occur much more frequently than described in inbred mice. Detailed sequence analysis of one provirus shows that solo-LTR formation occurred at least three separate times in recent history. An unoccupied preintegration site also was present at this locus in two individuals, indicating that although the age of this provirus is estimated to be approximate to1.2 million years, it has not yet become fixed in the human population.