A Long-Running Arms Race between Genes and Retroviruses in Tetrapods.

Activation-induced cytidine deaminase/apolipoprotein B mRNA editing catalytic polypeptide-like (AID/APOBEC) proteins are cytosine deaminases implicated in diverse biological functions. APOBEC1 (A1) proteins have long been thought to regulate lipid metabolism, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. Endogenous retroviruses (ERVs) document past retroviral infections and are ubiquitous within the vertebrate genomes. Here, we identify the gene repertoire, characterize the A1-mediated mutation footprints in ERVs, and interrogate the evolutionary arms race between genes and ERVs across vertebrate species. We find that genes are widely present in tetrapods, recurrently amplified and lost in certain lineages, suggesting that genes might have originated during the early evolution of tetrapods. A1-mediated mutation footprints can be detected in ERVs across tetrapods. Moreover, genes appear to have experienced episodic positive selection in many tetrapod lineages. Taken together, we propose that a long-running arms race between genes and retroviruses might have persisted throughout the evolutionary course of tetrapods. () genes have been thought to function in defense against retroviruses, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. In this study, we identify the gene repertoire, characterize the A1-mediated mutation footprints in endogenous retroviruses (ERVs), and explore the evolutionary arms race between genes and ERVs across vertebrate species. We found A1 proteins originated during the early evolution of tetrapods, and detected the footprints of A1-induced hypermutations in retroviral fossils. genes appear to have experienced pervasive positive selection in tetrapods. Our study indicates a long-running arms race between genes and retroviruses taking place throughout the evolutionary course of tetrapods.