Ancestral capture of syncytin-Car1 , a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora

Abstract

Syncytins are envelope protein genes of retroviral origin that have been captured for a function in placentation. Two such genes have already been identified in simians, two distinct, unrelated genes have been identified in Muridae, and a fifth gene has been identified in the rabbit. Here, we searched for similar genes in the Laurasiatheria clade, which diverged from Euarchontoglires—primates, rodents, and lagomorphs—shortly after mammalian radiation (100 Mya). In silico search for envelope protein genes with full-coding capacity within the dog and cat genomes identified several candidate genes, with one common to both species that displayed placenta-specific expression, which was revealed by RT-PCR analysis of a large panel of tissues. This gene belongs to a degenerate endogenous retroviral element, with precise proviral integration at a site common to dog and cat. Cloning of the gene for an ex vivo pseudotype assay showed fusogenicity on both dog and cat cells. In situ hybridization on placenta sections from both species showed specific expression at the level of the invasive fetal villi within the placental junctional zone, where trophoblast cells fuse into a syncytiotrophoblast layer to form the maternofetal interface. Finally, we show that the gene is conserved among a series of 26 Carnivora representatives, with evidence for purifying selection and conservation of fusogenic activity. The gene is not found in the Pholidota order and, therefore, it was captured before Carnivora radiation, between 60 and 85 Mya. This gene is the oldest syncytin gene identified to date, and it is the first in a new major clade of eutherian mammals.

Paleovirology of ‘ syncytins ’, retroviral env genes exapted for a role in placentation

“…This makes syncytin-Car1 the oldest known syncytin gene. Both the dog and cat syncytin-Car1 display fusogenic activity and are specifically expressed in the placenta within the syncytiotrophoblast layer at the maternal-fetal interface [60]. Altogether, these studies provide clear evidence that a number of retroviral env genes have been independently coopted on multiple occasions in the course of mammalian evolution (figure 5) and may have thus repeatedly prompted the emergence of a syncytial maternal-fetal interface, exemplifying a remarkable phenomenon of evolutionary convergence.…”

“…Syncytin-Ory1 expression was detected in the placenta junctional zone, where the invading placental syncytia come into contact with the maternal decidua, suggesting its possible involvement in syncytiotrophoblast formation. More recently, a sixth functional syncytin gene, syncytin-Car1, was found to be present in the 26 species of carnivores investigated [60]. Carnivores are members of the Laurasiatheria superorder, which diverged from the Euarchontoglires more than 80 Ma.…”

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

“…In situ hybridization experiments using syncytin-Ten1 sequences as a probe clearly show that specific expression takes place at the level of the multinucleate syncytial structures generated at the feto-maternal interface of the placenta, consistent with this fusogenic syncytin gene having a direct role in syncytium formation. Syncytin-Ten1 adds to the syncytin genes previously identified in the Euarchontoglires and Laurasiatheria clades, with the two primate syncytin-1 and -2 genes (3-5), the two Muroidea syncytin-A and -B genes (7), the Leporidae syncytin-Ory1 gene (8), and the syncytin-Car1 and syncytin-Rum1 genes recently identified in the Carnivora and Ruminantia, respectively (9,10). Identification of syncytinTen1 clearly establishes that syncytin capture extends beyond the Boreoeutheria superorder within eutherian mammals, with syncytin-Ten1 being, to our knowledge, the first syncytin gene identified to date in the ancestrally diverged Atlantogenata superorder.…”

“…(7) Higher magnification of the views in 5 demonstrating the absence of a cellular membrane between nuclei (nu). (8 and 9) Higher magnifications of the cells in 6 centered on the interface between the syncytium and the uterine epithelium (8) or the maternal endothelial cell (9). Note the space between the syncytium and the epithelial or the endothelial cellular membranes (indicated by arrowheads), suggesting that the basal membrane of these cells is not degraded by the syncytium at this stage.…”

Functional endogenous viral elements in the genome of the parasitoid wasp Cotesia congregata : insights into the evolutionary dynamics of bracoviruses

“…For example, different mammalian lineages have independently acquired retroviral genes that are known to be involved in placental development [11]. In the case of BVs, parasitoid wasps have co-opted a nudiviral genome to ensure virus particle production.…”