Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs

• Published in: Proceedings of the National Academy of Sciences - PNAS 2014-10, Vol.111 (41), p.E4332-E4341
• Main Authors: Cornelis, Guillaume, Vernochet, Cécile, Malicorne, Sébastien, Souquere, Sylvie, Tzika, Athanasia C, Goodman, Steven M, Catzeflis, François, Robinson, Terence J, Milinkovitch, Michel C, Pierron, Gérard, Heidmann, Odile, Dupressoir, Anne, Heidmann, Thierry
• Format: Article
• Language: English
• Subjects: Animals; Biodiversity and Ecology; Biological Sciences; Computer Simulation; Environmental Sciences; Evolution, Molecular; Female; Gene Products, env - genetics; Genome - genetics; In Situ Hybridization; Insectivora - genetics; Molecular Sequence Data; Phylogeny; Placenta - cytology; Placenta - ultrastructure; Placentation - genetics; PNAS Plus; Pregnancy; Pregnancy Proteins - genetics; Proviruses - genetics; Real-Time Polymerase Chain Reaction; Retroviridae - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Selection, Genetic; Time Factors; Virus Integration - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1412268111

Significance Syncytins are genes of retroviral origin that have been captured by their host as symbionts for a function in placentation. They can mediate cell–cell fusion, consistent with their ancestral retroviral envelope gene status, and are involved in fusion of mononucleate trophoblast cells to form the syncytial layer—the syncytiotrophoblast—of the feto–maternal interface. We proposed that such genes have been pivotal for the emergence of placental mammals from egg-laying animals and should be present all along the Placentalia radiation. We searched for syncytins in a superorder of eutherian mammals that emerged ancestrally during the Cretaceous terrestrial revolution and identified syncytin-Ten1 , conserved over millions years of evolution of the Afrotherian tenrecs, regarded as among the most primitive of living mammals. 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.