Maternal-Fetal Conflict: Rapidly Evolving Proteins in the Rodent Placenta

Conflicting evolutionary interests between mother and offspring are hypothesized to drive an evolutionary arms race during mammalian pregnancy, and thus, positive selection may cause the rapid divergence of placental proteins that affect maternal or fetal fitness. We investigated the genomic consequences of placental expression in rodents and report that a substantial proportion (20.5%) of genes specifically expressed in the mature placenta are rapidly evolving. Moreover, we found that most rapidly evolving genes belong to just three pregnancy-related gene families: placental cathepsins, prolactins, and placental carcinoembryonic antigens. We then sequenced the most rapidly evolving gene, trophoblast-specific protein alpha (Tpbpa), in nine different Mus species/subspecies and found evidence of positive selection within the Mus lineage, with an excess of nonsynonymous changes clustering near a functionally important interaction site. Together, these results suggest that placental proteins, which mediate interactions between mother and offspring, often may be the targets of evolutionary conflict.