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“合胞素”的古病毒学:逆转录病毒外显子基因被特化用于胎盘形成。

Paleovirology of 'syncytins', retroviral env genes exapted for a role in placentation.

机构信息

UMR 8122, Unité des Rétrovirus Endogènes et Éléments Rétroïdes des Eucaryotes Supérieurs, CNRS, Institut Gustave Roussy, , 94805 Villejuif, France.

出版信息

Philos Trans R Soc Lond B Biol Sci. 2013 Aug 12;368(1626):20120507. doi: 10.1098/rstb.2012.0507. Print 2013 Sep 19.

Abstract

The development of the emerging field of 'paleovirology' allows biologists to reconstruct the evolutionary history of fossil endogenous retroviral sequences integrated within the genome of living organisms and has led to the retrieval of conserved, ancient retroviral genes 'exapted' by ancestral hosts to fulfil essential physiological roles, syncytin genes being undoubtedly among the most remarkable examples of such a phenomenon. Indeed, syncytins are 'new' genes encoding proteins derived from the envelope protein of endogenous retroviral elements that have been captured and domesticated on multiple occasions and independently in diverse mammalian species, through a process of convergent evolution. Knockout of syncytin genes in mice provided evidence for their absolute requirement for placenta development and embryo survival, via formation by cell-cell fusion of syncytial cell layers at the fetal-maternal interface. These genes of exogenous origin, acquired 'by chance' and yet still 'necessary' to carry out a basic function in placental mammals, may have been pivotal in the emergence of mammalian ancestors with a placenta from egg-laying animals via the capture of a founding retroviral env gene, subsequently replaced in the diverse mammalian lineages by new env-derived syncytin genes, each providing its host with a positive selective advantage.

摘要

新兴的“古病毒学”领域的发展使生物学家能够重建整合在生物体内基因组中的化石内源性逆转录病毒序列的进化史,并导致检索到保守的、古老的逆转录病毒基因,这些基因被祖先宿主“适应”来发挥重要的生理作用,合胞素基因无疑是这种现象的最显著例子之一。事实上,合胞素是“新”基因,编码的蛋白质来自内源性逆转录病毒元件的包膜蛋白,这些基因已经被捕获并在多种哺乳动物物种中独立地多次驯化,通过趋同进化的过程。在小鼠中敲除合胞素基因的证据表明,它们对于胎盘发育和胚胎存活是绝对必需的,这是通过胎儿-母体界面的细胞融合形成合胞层来实现的。这些外源性起源的基因是“偶然”获得的,但对于胎盘哺乳动物执行基本功能仍然是必需的,它们可能在哺乳动物祖先从产卵动物通过捕获一个创始的逆转录病毒 env 基因进化而来的过程中发挥了关键作用,随后在不同的哺乳动物谱系中被新的 env 衍生的合胞素基因所取代,每个基因都为其宿主提供了一个积极的选择优势。

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