Placenta-Driven Evolution: Viral Gene Acquisition and PEG10's Essential Roles in Eutherian Placenta

Mammalian placentation represents one of the most striking evolutionary innovations among vertebrates, and accumulating evidence indicates that virus-derived genes-particularly the metavirus-derived PEG10 and PEG11/RTL1-have played indispensable but distinct roles: PEG10 in the emergence of therian viviparity and PEG11/RTL1 in the subsequent differentiation between marsupial and eutherian placental types. Notably, the metavirus-derived SIRH/RTL gene group, which includes PEG10 and PEG11/RTL1, exhibits unique and diverse functions not only in placenta development but also within microglia of the brain. Because microglia originate from yolk sac progenitors, these findings suggest that extraembryonic tissues such as the placenta and yolk sac provided permissive environments that enabled the retention, expression and functional domestication of virus-derived sequences. Once the placenta itself was established through viral gene integration, it may in turn have acted as a powerful driver of eutherian evolution through recurrent acquisition and co-option of additional virus-derived genes-a process we refer to as "placenta-driven evolution." This perspective offers a unified framework in which viral gene acquisition is viewed as a key driver of genomic innovation, tightly intertwined with the emergence of viviparity, subsequent divergence at the marsupial-eutherian split, and continued diversification of placental structure and function across eutherian lineages.