Retroviruses have had a tremendous impact on animal genomes. At least eight percent of the human genome is comprised of retroviruses at various stages of “fossilization”. These elements represent retroviruses that have directly infected genomes of germline tissues such that their imprints can now be passed on with the rest of the genome. Most insertions into host genomes are likely to (i) be instantly so deleterious that they are never passed on, or alternatively (ii) have very little consequence to host biology and be expected to abrade away via the accumulation of mutations. Although the large fraction of retroviral imprints show expected signatures of mutational degeneration, some retroviral genes have been surprisingly preserved against mutational inactivation. These represent instances in which host genomes have usurped some retroviral genes for their own use. Particularly intriguing are host domestications of retroviral envelope (env) genes. The best-known classes of these genes are the syncytin genes, which have been coopted by the host to mediate nutrient transfer from the mother to the developing embryo in mammals.
Ancestral capture of syncytin-Car1, a fusogenic endogenous retroviral envelope gene involved in placentation and conserved in Carnivora. PNAS USA 17 January 2012 doi: 10.1073/pnas.1115346109
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.