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

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Summary Paragraph The genus Myotis is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense 1–3 . 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 to all other mammals, with bats exhibiting genome-wide overrepresentation 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 protein kinase R ( 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 M. lucifugus . Together, our results suggest that bats’ remarkable longevity and immunity are linked through pleiotropic adaptations to viruses and aging-related disease.

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