Retroviral envelope gene captures and syncytin exaptation for placentation in marsupials

Significance Syncytins are “captured” genes of retroviral origin, corresponding to the fusogenic envelope gene of endogenized retroviruses. They are present in a series of eutherian mammals, including humans and mice where they play an essential role in placentation. Here we show that marsupials—which diverged from eutherian mammals ∼190 Mya but still possess a primitive, short-lived placenta (rapidly left by the embryo for development in an external pouch)—have also captured such genes. The present characterization of the syncytin-Opo1 gene in the opossum placenta, together with the identification of two additional endogenous retroviral envelope gene captures, allow a recapitulation of the natural history of these unusual genes and definitely extends their “symbiotic niche” to all clades of placental mammals. Syncytins are genes of retroviral origin captured by eutherian mammals, with a role in placentation. Here we show that some marsupials—which are the closest living relatives to eutherian mammals, although they diverged from the latter ∼190 Mya—also possess a syncytin gene. The gene identified in the South American marsupial opossum and dubbed syncytin-Opo1 has all of the characteristic features of a bona fide syncytin gene: It is fusogenic in an ex vivo cell–cell fusion assay; it is specifically expressed in the short-lived placenta at the level of the syncytial feto–maternal interface; and it is conserved in a functional state in a series of Monodelphis species. We further identify a nonfusogenic retroviral envelope gene that has been conserved for >80 My of evolution among all marsupials (including the opossum and the Australian tammar wallaby), with evidence for purifying selection and conservation of a canonical immunosuppressive domain, but with only limited expression in the placenta. This unusual captured gene, together with a third class of envelope genes from recently endogenized retroviruses—displaying strong expression in the uterine glands where retroviral particles can be detected—plausibly correspond to the different evolutionary statuses of a captured retroviral envelope gene, with only syncytin-Opo1 being the present-day bona fide syncytin active in the opossum and related species. This study would accordingly recapitulate the natural history of syncytin exaptation and evolution in a single species, and definitely extends the presence of such genes to all major placental mammalian clades.