Ancient Evolutionary Origin and Positive Selection of the Retroviral Restriction FactorFv1in Muroid Rodents

Retroviruses have adapted to living in concert with their hosts throughout vertebrate evolution. Over the years, the study of these relationships revealed the presence of host proteins called restriction factors that inhibit retroviral replication in host cells. The first of these restriction factors to be identified, encoded by theFv1 gene found in mice, was thought to have originated in the genusMus . In this study, we utilized genome database searches and DNA sequencing to identifyFv1 copies in multiple rodent lineages. Our findings suggest a minimum time of insertion into the genome of rodents of 45 million years for the ancestral progenitor ofFv1 . WhileFv1 is not detectable in some lineages, we also identified full-length orthologs showing signatures of a molecular “arms race” in a family of rodent species indigenous to Africa. This finding suggests thatFv1 in these species has been coevolving with unidentified retroviruses for millions of years.