The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology
The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology
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DOI：
10.1073/pnas.0305763101
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发表时间：
2004-02-10
影响因子：
11.1
通讯作者：
Mandrand, B
中科院分区：
文献类型：
--
作者：
Mallet, F;Bouton, O;Mandrand, B
明确证明最近获得的基因的作用是一项艰巨的任务，需要进行详尽的遗传研究和功能分析。当面对多拷贝基因家族时，情况确实要复杂得多，因为基因的大部分或部分在该家族的数百个拷贝中是保守的。人内源性逆转录病毒 W 家族 (HERV-W) 的 ERVWE1 基因座就是这种情况，该基因座编码可能参与滋养层分化的包膜糖蛋白（合胞素）。在这里，我们在 155 个个体中描述了该基因座的位置保守性和包膜 ORF 的保存。 ERVWE1 原病毒关键元件的测序显示，24 个个体的 48 个等位基因之间存在惊人的保守性，包括参与转录机制的 LTR 元件、参与亚基因组 Env mRNA 成熟的剪接位点以及 Env ORF。 5' LTR 的功能和组织特异性以及包膜多态性变体的融合活性得到了证明。这些功能也被证明保留在从黑猩猩、大猩猩、猩猩和长臂猿中分离的直系同源基因座中。这种在人类和进化过程中的功能保留有力地证明了这种最近获得的逆转录病毒包膜糖蛋白参与了类人猿胎盘生理学。
The definitive demonstration of a role for a recently acquired gene is a difficult task, requiring exhaustive genetic investigations and functional analysis. The situation is indeed much more complicated when facing multicopy gene families, because most or portions of the gene are conserved among the hundred copies of the family. This is the case for the ERVWE1 locus of the human endogenous retrovirus W family (HERV-W), which encodes an envelope glycoprotein (syncytin) likely involved in trophoblast differentiation. Here we describe, in 155 individuals, the positional conservation of this locus and the preservation of the envelope ORF. Sequencing of the critical elements of the ERVWE1 provirus showed a striking conservation among the 48 alleles of 24 individuals, including the LTR elements involved in the transcriptional machinery, the splice sites involved in the maturation of subgenomic Env mRNA, and the Env ORF. The functionality and tissue specificity of the 5' LTR were demonstrated, as well as the fusogenic activity of the envelope polymorphic variants. Such functions were also shown to be preserved in the orthologous loci isolated from chimpanzee, gorilla, orangutan, and gibbon. This functional preservation among humans and during evolution strongly argued for the involvement of this recently acquired retroviral envelope glycoprotein in hominoid placental physiology.