title: Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs.
abstract: Syncytins are fusogenic envelope (env) genes of retroviral origin that have been captured for a function in placentation. Syncytins have been identified in Euarchontoglires (primates, rodents, Leporidae) and Laurasiatheria (Carnivora, ruminants) placental mammals. Here, we searched for similar genes in species that retained characteristic features of primitive mammals, namely the Malagasy and mainland African Tenrecidae. They belong to the superorder Afrotheria, an early lineage that diverged from Euarchotonglires and Laurasiatheria 100 Mya, during the Cretaceous terrestrial revolution. An in silico search for env genes with full coding capacity within a Tenrecidae genome identified several candidates, with one displaying placenta-specific expression as revealed by RT-PCR analysis of a large panel of Setifer setosus tissues. Cloning of this endogenous retroviral env gene demonstrated fusogenicity in an ex vivo cell-cell fusion assay on a panel of mammalian cells. Refined analysis of placental architecture and ultrastructure combined with in situ hybridization demonstrated specific expression of the gene in multinucleate cellular masses and layers at the materno-fetal interface, consistent with a role in syncytium formation. This gene, which we named "syncytin-Ten1," is conserved among Tenrecidae, with evidence of purifying selection and conservation of fusogenic activity. To our knowledge, it is the first syncytin identified to date within the ancestrally diverged Afrotheria superorder.
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France; Université Paris Denis Diderot, Sorbonne Paris-Cité, 75013 Paris, France;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cornelis
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Cécile
authors.initials: C
authors.lastname: Vernochet
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Malicorne
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Sylvie
authors.initials: S
authors.lastname: Souquere
authors.affiliation: Laboratory of Artificial and Natural Evolution, Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Genève 4, Switzerland;
authors.forename: Athanasia C
authors.initials: AC
authors.lastname: Tzika
authors.affiliation: Association Vahatra, BP 3972, Antananarivo 101, Madagascar; Field Museum of Natural History, Chicago, IL 60605;
authors.forename: Steven M
authors.initials: SM
authors.lastname: Goodman
authors.affiliation: Laboratoire de Paléontologie, Phylogénie et Paléobiologie, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5554, Université Montpellier II, 34095 Montpellier, France; and.
authors.forename: François
authors.initials: F
authors.lastname: Catzeflis
authors.affiliation: Evolutionary Genomics Group, Department of Botany and Zoology, University of Stellenbosch, Matieland 7602, South Africa.
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Robinson
authors.affiliation: Laboratory of Artificial and Natural Evolution, Department of Genetics and Evolution, University of Geneva, Sciences III, 1211 Genève 4, Switzerland;
authors.forename: Michel C
authors.initials: MC
authors.lastname: Milinkovitch
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Gérard
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Odile
authors.initials: O
authors.lastname: Heidmann
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Dupressoir
authors.affiliation: Unité des Rétrovirus Endogènes et Eléments Rétroïdes des Eucaryotes Supérieurs, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8122, Institut Gustave Roussy, 94805 Villejuif, France; Université Paris-Sud, 91405 Orsay, France; heidmann@igr.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Heidmann
mesh_terms: D000818:Animals; D003198:Computer Simulation; D007312:Eulipotyphla / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D015686:Gene Products, env / Q000235:genetics*; D016678:Genome / Q000235:genetics; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010802:Phylogeny; D010920:Placenta / Q000166:cytology / Q000648:ultrastructure; D010929:Placentation / Q000235:genetics*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics*; D012641:Selection, Genetic; D013997:Time Factors; D016662:Virus Integration / Q000235:genetics
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C405335:syncytin
keywords: endogenous retrovirus; envelope protein; feto–maternal interface; placenta evolution; syncytiotrophoblast