From ancestral infectious retroviruses to bona fide cellular genes: Role of the captured syncytins in placentation
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). "
ABSTRACT: Giant Viruses are a widespread group of viruses, characterized by huge genomes composed of a small subset of ancestral, vertically inherited core genes along with a large body of highly variable genes. In this study, I report the acquisition of 23 core ancestral Giant Virus genes by diverse eukaryotic species including various protists, a moss and a cnidarian. The viral genes are inserted in large scaffolds or chromosomes with intron-rich, eukaryotic-like genomic contexts, refuting the possibility of DNA contaminations. Some of these genes are expressed and in the cryptophyte alga Guillardia theta, a possible non-homologous displacement of the eukaryotic DNA primase by a viral D5 helicase/primase is documented. As core Giant Virus genes represent only a tiny fraction of the total genomic repertoire of these viruses, these results suggest that Giant Viruses represent an underestimated source of new genes and functions for their hosts.Virology 07/2014; 466. DOI:10.1016/j.virol.2014.06.004 · 3.28 Impact Factor
- "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. "
Article: What is a genome?[Show abstract] [Hide abstract]
ABSTRACT: The field of genomics is expanding rapidly, yet the meanings of the word ‘genome’ have yet to be conceptualized in explicit, coherent and useful frameworks. We develop and apply an evolutionary conceptualization of the genome,which represents a logical extension of the evolutionary definition of a gene developed by George C.Williams. An evolutionary genome thus represents a set of genetic material, in a lineage, that due to common interests tends to favour the same or similar phenotypes.This conceptualization provides novel perspectives on genome functions, boundaries and evolution, which should help to guide theoretical and empirical genomics research.Molecular Ecology 07/2013; 22(13):3437-43. DOI:10.1111/mec.12355 · 6.49 Impact Factor
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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. "
ABSTRACT: Recent studies suggested a role for the human endogenous retrovirus group HERV-K(HML-2) in melanoma because of upregulated transcription and expression of HERV-K(HML-2) encoded proteins. Very little is known about which HML-2 loci are transcribed in melanoma. We assigned >1,400 HML-2 cDNA sequences generated from various melanoma and related samples to genomic HML-2 loci, identifying a total of 23 loci as transcribed. Transcription profiles of loci differed significantly between samples. One locus was found transcribed only in melanoma-derived samples but not in melanocytes and might represent a marker for melanoma. Several of the transcribed loci harbor ORFs for retroviral Gag and/or Env proteins. Env encoding loci were transcribed only in melanoma. Specific investigation of rec and np9 transcripts indicated transcription of protein encoding loci in melanoma and melanocytes hinting at the relevance of Rec and Np9 in melanoma. UVB irradiation changed transcription profiles of loci and overall transcript levels decreased in melanoma and melanocytes. We furthermore identified transcribed HML-2 loci formed by reverse transcription of spliced HML-2 transcripts by L1 machinery or in a retroviral fashion, with loci potentially encoding HML-2 like proteins. We reveal complex, sample-specific transcription of HML-2 loci in melanoma and related samples. Identified HML-2 loci and proteins encoded by those loci are particularly relevant for further studying the role of HML-2 in melanoma. Transcription of HERVs appears as a complex mechanism requiring specific studies to elucidate which HERV loci are transcribed and how transcribed HERVs may be involved in disease.Genome Biology and Evolution 01/2013; 5(2). DOI:10.1093/gbe/evt010 · 4.53 Impact Factor