title: The captured retroviral envelope syncytin-A and syncytin-B genes are conserved in the Spalacidae together with hemotrichorial placentation.
abstract: Syncytins are fusogenic envelope (env) genes of retroviral origin that have been captured for a function in placentation. Multiple independent events of syncytin gene capture were found to have occurred in primates, rodents, lagomorphs, carnivores, and ruminants. In the mouse, two syncytin-A and -B genes are present, which trigger the formation of the two-layered placental syncytiotrophoblast at the maternal-fetal interface, a structure classified as hemotrichorial. Here, we identified syncytin-A and -B orthologous genes in the genome of all Muroidea species analyzed, thus dating their capture back to about at least 40 million years ago, with evidence that they evolved under strong purifying selection. We further show, in the divergent Spalacidae lineage (blind mole rats [Spalax]), that both syncytins have conserved placenta-specific expression, as revealed by RT-PCR analysis of a panel of Spalax galili tissues, and display fusogenic activity, using ex vivo cell-cell fusion assays. Refined analysis of the placental architecture and ultrastructure revealed that the Spalax placenta displays a hemotrichorial organization of the interhemal membranes, as similarly observed for other Muroidea species, yet with only one trophoblastic cell layer being clearly syncytialized. In situ hybridization experiments further localized syncytin transcripts at the level of these differentiated interhemal membranes. These findings argue for a role of syncytin gene capture in the establishment of the original hemotrichorial placenta of Muroidea, and more generally in the diversity of placental structures among mammals.
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, Villejuif, France Université Paris-Sud, 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, Villejuif, France Université Paris-Sud, Orsay, France.
authors.forename: François
authors.initials: F
authors.lastname: Redelsperger
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, Villejuif, France Université Paris-Sud, Orsay, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Harper
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, Villejuif, France Université Paris-Sud, Orsay, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Souquere
authors.affiliation: Laboratoire de Paléontologie, Phylogénie et Paléobiologie, Centre National de la Recherche Scientifique, Université Montpellier II, Montpellier, France.
authors.forename: François
authors.initials: F
authors.lastname: Catzeflis
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, Villejuif, France Université Paris-Sud, Orsay, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Pierron
authors.affiliation: Institute of Evolution, University of Haifa, Mount Carmel, Haifa, Israel.
authors.forename: Eviatar
authors.initials: E
authors.lastname: Nevo
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, Villejuif, France Université Paris-Sud, Orsay, France thierry.heidmann@igr.fr.
authors.forename: Thierry
authors.initials: T
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, Villejuif, France Université Paris-Sud, Orsay, France dupresso@igr.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Dupressoir
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003411:Arvicolinae; D017124:Conserved Sequence; D006224:Cricetinae; D020077:Endogenous Retroviruses / Q000235:genetics*; D005260:Female; D015686:Gene Products, env / Q000235:genetics*; D051379:Mice; D019577:Mole Rats; D008969:Molecular Sequence Data; D010802:Phylogeny; D010929:Placentation / Q000235:genetics; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D046308:Spalax / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D014759:Viral Envelope Proteins; C405335:syncytin
keywords: Spalax; blind mole rat; cell-cell fusion; endogenous retrovirus; envelope protein; maternal-fetal interface; placenta evolution; placentation; rodents; syncytiotrophoblast