1 Cross - species transmission and differential fate of an 1 endogenous retrovirus in three mammal lineages

8. CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not. ABSTRACT 9 Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in 1 0 the host germline. ERVs are common in vertebrate genomes and provide a valuable 1 1 fossil record of past retroviral infections to investigate the biology and evolution of 1 2 retroviruses over a deep time scale, including cross-species transmission events. Here 1 3 we took advantage of a catalog of ERVs we recently produced for the bat Myotis 1 4 lucifugus to seek evidence for infiltration of these retroviruses in other mammalian 1 5 species (>100) currently represented in the genome sequence database. We provide 1 6 multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus 1 7 endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin 1 8 ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively 1 9 in parallel in both bat and cat lineages, generating hundreds of species-specific 2 0 insertions throughout evolution. However, despite being derived from the same viral 2 1 species, phylogenetic and selection analyses suggest that the ERV experienced 2 2 different amplification dynamics in the two mammalian lineages. In the cat lineage, the 2 3 ERV appears to have expanded primarily by retrotransposition of a single proviral 2 4 progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, 2 5 the ERV followed a more complex path of germline invasion characterized by both 2 6 retrotransposition and multiple infection events. The results also suggest that some of 2 7 the bat ERVs have maintained infectious capacity for extended period of time and may 2 8 be still infectious today. This study provides one of the most rigorously documented 2 9 cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the 3 0 same retrovirus species has transitioned multiple times from an infectious pathogen to a 3