Insights into longevity and virus-driven adaptation from Myotis bat genomes

The genus Myotis is one of the largest clades of bats, and it exhibits some of the most extreme variation in lifespans among mammals, alongside unique adaptations to viral tolerance and immune defence^1-3. Here, to study the evolution of these phenotypes, we generated cell lines and near-complete genome assemblies for eight closely related Myotis species. Using genome-wide screens of positive selection, analyses of structural variation and functional experiments in primary cells, we identify patterns of adaptation contributing to longevity, cancer resistance and viral interactions. We demonstrate distinct modes of adaptation to DNA and RNA viruses compared with all other mammals, with bats exhibiting genome-wide over-representation of positive selection for DNA-virus-interacting proteins and elevated rates of copy-number variation for RNA-virus-interacting proteins. Characterization of Myotis-specific duplications of the key immune factor EIF2AK2 (also known as PKR) reveals multiple ancient segregating trans-species copy-number polymorphisms. We show that the recurrent evolution of longevity seen in Myotis is associated with positive selection in cancer pathways, and demonstrate a unique response to DNA damage in primary cells of the long-lived Myotis lucifugus. Together, our results suggest that bats' remarkable longevity and immunity are linked through pleiotropic adaptations to viruses and ageing-related disease.