Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): Implications for present-day activity
Genomewide screening reveals high levels of insertional polymorphism in the human endogenous retrovirus family HERV-K(HML2): Implications for present-day activity
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DOI：
10.1128/jvi.79.19.12507-12514.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Tristem, M
中科院分区：
文献类型：
--
作者：
Belshaw, R;Dawson, ALA;Tristem, M
已公布的人类基因组序列包含数千种内源性逆转录病毒(HERV)，但都是有缺陷的，包含无义突变或重大缺失。自从人类和黑猩猩分化以来，只有Herv-K(HML2)家族是活跃的；它包含许多人类特有的成员，以及几个插入多态的成员(插入的元件只存在于某些人类个体中)。在这里，我们利用已发表的人类基因组序列和19个人的不同样本，对该家族的插入多态水平进行了全基因组调查。我们发现在人类基因组序列中有113个人类特有的Herv-K(HML2)元件，其中8个是插入多态的(如果我们推断到基因组中不适合扩增的区域有11个)。因此，由于与黑猩猩的分化，每代单倍体基因组的平均积累速度约为3.8x10(-4)。此外，我们发现，多态元件的数量与标准种群遗传模型预测的数量没有显著差异，该模型假定到目前为止，家庭的活动是恒定的。这向我们暗示HERV-K(HML2)家族在今天的人类中可能是活跃的。活性(复制能力)元素很可能是最近插入的，并且以低等位基因频率存在，它们可能会在携带它们的个体中引起疾病。这种从人口角度而不是基因组角度对家庭的看法将为当前关于HERV-K(HML2)在人类疾病中可能扮演的角色的辩论提供信息。
The published human genome sequence contains many thousands of endogenous retroviruses (HERVs) but all are defective, containing nonsense mutations or major deletions. Only the HERV-K(HML2) family has been active since the divergence of humans and chimpanzees; it contains many members that are human specific, as well as several that are insertionally polymorphic (an inserted element present only in some human individuals). Here we perform a genomewide survey of insertional polymorphism levels in this family by using the published human genome sequence and a diverse sample of 19 humans. We find that there are 113 human-specific HERV-K(HML2) elements in the human genome sequence, 8 of which are insertionally polymorphic (11 if we extrapolate to those within regions of the genome that were not suitable for amplification). The average rate of accumulation since the divergence with chimpanzees is thus approximately 3.8 x 10(-4) per haploid genome per generation. Furthermore, we find that the number of polymorphic elements is not significantly different from that predicted by a standard population genetic model that assumes constant activity of the family until the present. This suggests to us that the HERV-K(HML2) family may be active in present-day humans. Active (replication-competent) elements are likely to have inserted very recently and to be present at low allele frequencies, and they may be causing disease in the individuals carrying them. This view of the family from a population perspective rather than a genome perspective will inform the current debate about a possible role of HERV-K(HML2) in human disease.