title: Evidence of selection on the domesticated ERVWE1 env retroviral element involved in placentation.
abstract: 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.
authors.affiliation: UMR 2714 CNRS-bioMérieux IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bonnaud
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouton
authors.forename: Guy
authors.initials: G
authors.lastname: Oriol
authors.forename: Valérie
authors.initials: V
authors.lastname: Cheynet
authors.forename: Laurent
authors.initials: L
authors.lastname: Duret
authors.forename: François
authors.initials: F
authors.lastname: Mallet
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D018626:Retroelements; D012641:Selection, Genetic
chemical_list: D018626:Retroelements