From ancestral infectious retroviruses to bona fide cellular genes: Role of the captured syncytins in placentation

Unité des Rétrovirus Endogènes et Éléments Rétroïdes des Eucaryotes Supérieurs, CNRS, UMR 8122, Institut Gustave Roussy, 114 rue Édouard Vaillant, 94805 Villejuif, France.
Placenta (Impact Factor: 3.29). 06/2012; 33(9):663-71. DOI: 10.1016/j.placenta.2012.05.005
Source: PubMed

ABSTRACT During their replication, infectious retroviruses insert a reverse-transcribed cDNA copy of their genome, a "provirus", into the genome of their host. If the infected cell belongs to the germline, the integrated provirus can become "fixed" within the host genome as an endogenous retrovirus and be transmitted vertically to the progeny in a Mendelian fashion. Based on the numerous proviral sequences that are recovered within the genomic DNA of vertebrates--up to ten percent in the case of mammals--such events must have occurred repeatedly during the course of millions of years of evolution. Although most of the ancient proviral sequences have been disrupted, a few "endogenized" retroviral genes are conserved and still encode functional proteins. In this review, we focus on the recent discovery of genes derived from the envelope glycoprotein-encoding (env) genes of endogenous retroviruses that have been domesticated by mammals to carry out an essential function in placental development. They were called syncytins based on the membrane fusogenic capacity that they have kept from their parental env gene and which contributes to the formation of the placental fused cell layer called the syncytiotrophoblast, at the materno-fetal interface. Remarkably, the capture of syncytin or syncytin-like genes, sometimes as pairs, was found to have occurred independently from different endogenous retroviruses in diverse mammalian lineages such as primates--including humans--, muroids, leporids, carnivores, caviids, and ovis, between around 10 and 85 million years ago. Knocking out one or both mouse syncytin-A and -B genes provided evidence that they indeed play a critical role in placentation. We discuss the possibility that the immunosuppressive domain embedded within retroviral envelope glycoproteins and conserved in syncytin proteins, may be involved in the tolerance of the fetus by the maternal immune system. Finally, we speculate that the capture of a founding syncytin-like gene could have been instrumental in the dramatic transition from egg-laying to placental mammals.

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    • "As a matter of fact, clear proofs of gene transfers viruses to hosts are encountered typically with genes widespread in viruses but that have no (or very distantly related) homologs in cellular genomes. Within the few examples reported till date, the syncytin genes promoting the formation of the placenta in mammals are clear cases of domestication of retroviral envelope genes (Dupressoir et al., 2012). Another clear example is the mitochondrial RNA polymerase, DNA polymerase and DNA helicase that are derived from T3/T7 phage genes (Filee and Forterre, 2005). "
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    • "Vertical and horizontal inheritance and movement of viruses; gradual integration of viruses into host genomes Holmes (2011); Doerfler (2012); Dupressoir et al. (2012) Vertical and horizontal inheritance and movement of transposable elements with deleterious and beneficial effects on co-inherited genetic material; integration into host genomes Venner et al. (2009); de Carvalho & Loreto (2012); Rebollo et al. (2012) Vertical and horizontal inheritance and movement of microbes with, within and across hosts Lederberg (2000); Ley et al. (2006); Moran et al. (2008); Zilber-Rosenberg & Rosenberg (2008); Koga et al. (2012) important dimension, provided that evidence for function comes from studies of purifying or positive selection. Research programmes may concentrate now on the officially designated genes in databases, but natural selection and evolution only see them, as entities, to the extent that they correspond to the evolutionary view. "
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    • "The syncytin-1/ERVWE1 gene is, in essence, a proviral locus of the HERV-W group. The Env protein of that HERV-W locus, named Syncytin-1, has been selected during evolution for contributing to fusion of cell membranes of trophoblasts to form syncytiotrophoblasts, which is an essential process during human placenta formation (Mallet et al. 2004; Dupressoir et al. 2012). The HERV-K(HML-2) group, in short, HML-2, is exceptional regarding evolution, coding capacity and potential clinical involvement. "
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