Retroviruses push the envelope for mammalian placentation.

R etroviruses have had a tremendous, recurring impact on animal genomes. At least eight percent of the human genome is comprised of retroviruses at various stages of “fossilization” (1). 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 (2). 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 eutherian mammals. In PNAS, Dupressoir and coworkers describe the oldest known domestication of retroviral envelopes represented by the Syncytin-Car1 gene (3), which was domesticated at least 60 Mya, before the radiation of Carnivora. These results extend the range and age of syncytin domestications in mammals, but also raise intriguing questions about the biology underlying their recurrent invention. Domestication of the syncytin genes represents a dramatic example of convergent evolution via the cooption of a retroviral gene for a key biological function in reproductive biology. In fact, syncytin domestication from a retroviral envelope gene has been previously shown to have independently occurred at least seven times during mammalian evolution (4–9). In the context of retroviral genomes, the env gene encodes a protein precursor that is cleaved into surface (SU) and transmembrane (TM) proteins that allow virions to attach to target cells and penetrate the cell membrane by fusion. SU protein serves to bind the virion to the host cell by interactions with receptors on the cell surface, whereas the TM protein serves to anchor the entire viral glycoprotein complex on the virion surface and to mediate the fusion of the virion with the host-cell membrane during entry. Many envelope proteins also encode a short peptide motif within the TM domain that has potent immunosuppressive activities, suppressing the production of cytokines and cell-mediated immunity (10). Intriguingly, these two activities—the abilities to