Evidence of selection on the domesticated ERVWE1 env retroviral element involved in placentation
Evidence of selection on the domesticated ERVWE1 env retroviral element involved in placentation
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DOI：
10.1093/molbev/msh206
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发表时间：
2004-10-01
影响因子：
10.7
通讯作者：
Mallet, F
中科院分区：
文献类型：
--
作者：
Bonnaud, B;Bouton, O;Mallet, F
人类内源性逆转录病毒HERV-W多拷贝家族包括一个独特的前病毒位点，称为ERVWE1，它包含gag和pol假基因，并保留全长包膜开放阅读框（ORF）。这种Env蛋白（合胞素）是一种高度融合的膜糖蛋白，被认为与类人猿胎盘生理有关。为了追踪作用于ERVWE1环境基因的自然选择标志，我们分析了所有人类HERV-W元件以及黑猩猩、大猩猩、猩猩和长臂猿的ERVWE1同源位点的替换和索引模式。ERVWE1和同源HERV-W拷贝的比较揭示了ERVWE1的特异性特征，包括糖蛋白胞浆内尾部的四个氨基酸缺失。我们发现这种缺失对包膜融合活性是至关重要的。人类ERVWE1基因座与其同源基因座的比较表明，存在一种保持环境阅读框打开的选择压力。值得注意的是，env基因的3'部分，编码融合过程所需的区域，正在进行纯化选择。对env ERVWE1的选择性约束的鉴定证实，这种逆转录病毒位点已经在类人猿谱系中被招募成为一个真正的基因。
The human endogenous retrovirus HERV-W multicopy family includes a unique proviral locus, termed ERVWE1, which contains gag and pol pseudogenes and has retained a full-length envelope open reading frame (ORF). This Env protein (syncytin) is a highly fusogenic membrane glycoprotein and has been proposed to be involved in hominoid placental physiology. To track the hallmarks of natural selection acting on the ERVWE1 env gene, the pattern of substitutions and indels was analyzed within all human HERV-W elements and along the ERVWE1 orthologous loci in chimpanzee, gorilla, orangutan, and gibbon. The comparison of ERVWE1 and paralogous HERV-W copies revealed an ERVWE1-specific signature consisting of a four amino acid deletion in the intracytoplasmic tail of the glycoprotein. We show that this deletion is crucial for the envelope fusogenic activity. The comparison of the human ERVWE1 locus with its orthologs demonstrates the existence of a selective pressure to maintain the env reading frame open. Notably, the 3' part of the env gene, encoding regions required for the fusion process, is under purifying selection. The identification of selective constraints on env ERVWE1 confirms that this retroviral locus has been recruited in the hominoid lineage to become a bona fide gene.