Retroviral envelope gene captures andsyncytinexaptation for placentation in marsupials

Abstract

Syncytinsare 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 asyncytingene. The gene identified in the South American marsupial opossum and dubbedsyncytin-Opo1has all of the characteristic features of a bona fidesyncytingene: 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 ofMonodelphisspecies. 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 onlysyncytin-Opo1being the present-day bona fidesyncytinactive in the opossum and related species. This study would accordingly recapitulate the natural history ofsyncytinexaptation and evolution in a single species, and definitely extends the presence of such genes to all major placental mammalian clades.