Doctor of Philosophy

dissertationEndogenous retroviruses (ERVs), derived from exogenous retroviruses (XRVs), comprise about 5 to 10 % of most mammalian genomes. We can study retroviral infection which originated millions years ago and understand long term evolution of infectious viruses by working on ERVs. At the same time, it has been suggested that multiple, new emerging viruses that infect human populations have been come from different bat species, and bats have become recognized as the reservoir of zoonotic viruses. However, we know little about retroviruses in bats. Here, we mined ERVs in the little brown bat genome, and found that the overall ERV amount in the little brown bat is comparable to other mammals. However, we still find hundreds of lineage-specific ERVs in the little brown bat genome. With identified bat ERVs, we subsequently investigated if there is any related retroviral cross-species transmission and independent endogenization. Using sequence homologous method to search bat ERV sequences against 107 available mammalian genomes, we found highly similar sequences in cat, tiger, and pangolin genomes in addition to related bat genomes. We found the ERV sequence is patchy distributed among mammalian lineages, and their high sequence similarity is incongruent with their host divergence. We also narrowed down the ERV insertion time to 10 to 20 million years ago. To understand how they evolved in different lineages, we investigated their evolution after integration in both bat and cat genomes. In the cat genome, the ERV lost its envelope domain and transformed to intracellular retrotransposon. While in the bat genome, multiple related infectious viruses became endogenized, and, at least in one lineage, the infectious capability has been maintained. Finally, I developed a computational pipeline and statistical framework which allows our method to be applied to the ERV population of virtually any species. When applied to 53 available vertebrate genomes, the approach identified ERVs previously known to have spread by reinfection in humans, mouse, and pig as well as additional ERV families carrying signature of recent infections in these and other species, including nonhuman primates, revealing their potential for zoonotic transmission