Molecular Fossils Illuminate The Evolution Of Retroviruses Following A Macroevolutionary Transition From Land To Water

Author summary The ancestor of cetaceans invaded the aquatic environments >50 million years ago. Recent comparative genomic studies have begun to reveal the molecular mechanisms underlying the morphological and ecological transformation of cetaceans. However, it has been largely obscure how retroviruses evolved during this land-to-water transition. Endogenous retroviruses (ERVs) recorded past retroviral infections. Here, we systematically mined and analyzed ERVs in the genomes of 25 cetaceans, and found that cetacean ERVs clustered into 315 distinct lineages. Among these cetacean ERV lineages, 298 lineages may originate through retrovirus endogenization before or during the colonization of aquatic environments by cetaceans, and 17 lineages may arise from endogenization of retroviruses that infected cetaceans through cross-species transmission from non-cetacean mammals after the transition to aquatic life of cetaceans. Taken together, our study provides a unique snapshot of the evolution of retroviruses during a major macroevolutionary transition.The ancestor of cetaceans underwent a macroevolutionary transition from land to water early in the Eocene Period >50 million years ago. However, little is known about how diverse retroviruses evolved during this shift from terrestrial to aquatic environments. Did retroviruses transition into water accompanying their hosts? Did retroviruses infect cetaceans through cross-species transmission after cetaceans invaded the aquatic environments? Endogenous retroviruses (ERVs) provide important molecular fossils for tracing the evolution of retroviruses during this macroevolutionary transition. Here, we use a phylogenomic approach to study the origin and evolution of ERVs in cetaceans. We identify a total of 8,724 ERVs within the genomes of 25 cetaceans, and phylogenetic analyses suggest these ERVs cluster into 315 independent lineages, each of which represents one or more independent endogenization events. We find that cetacean ERVs originated through two possible routes. 298 ERV lineages may derive from retrovirus endogenization that occurred before or during the transition from land to water of cetaceans, and most of these cetacean ERVs were reaching evolutionary dead-ends. 17 ERV lineages are likely to arise from independent retrovirus endogenization events that occurred after the split of mysticetes and odontocetes, indicating that diverse retroviruses infected cetaceans through cross-species transmission from non-cetacean mammals after the transition to aquatic life of cetaceans. Both integration time and synteny analyses support the recent or ongoing activity of multiple retroviral lineages in cetaceans, some of which proliferated into hundreds of copies within the host genomes. Although ERVs only recorded a proportion of past retroviral infections, our findings illuminate the complex evolution of retroviruses during one of the most marked macroevolutionary transitions in vertebrate history.