RT Journal Article SR Electronic T1 Long-read sequencing reveals rapid evolution of immunity- and cancer-related genes in bats JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.09.09.290502 DO 10.1101/2020.09.09.290502 A1 Armin Scheben A1 Olivia Mendivil Ramos A1 Melissa Kramer A1 Sara Goodwin A1 Sara Oppenheim A1 Daniel J Becker A1 Michael C Schatz A1 Nancy B Simmons A1 Adam Siepel A1 W Richard McCombie YR 2021 UL http://biorxiv.org/content/early/2021/08/19/2020.09.09.290502.abstract AB Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems. To investigate the genomic underpinnings of unique bat adaptations, we sequenced the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus) and compared them to a diverse collection of 13 additional bat species together with other mammals. We used the Oxford Nanopore Technologies long-read platform to generate highly complete assemblies (N50: 28-29Mb) and facilitate analysis of complex genomic regions containing duplicated genes. Using gene family size analysis, we found that the type I interferon locus was contracted by eight genes in the most recent common ancestor (MRCA) of bats, shifting the proportion of interferon-ω to interferon-α and making interferon-ω the most common type I interferon in bats. Antiviral genes stimulated by type I interferons were also rapidly evolving, with interferon-induced transmembrane genes experiencing a lineage-specific duplication and strong positive selection in the gene IFIT2. Moreover, the lineage of phyllostomid bats showed an unprecedented expansion of PRDM9, a recombination-related gene also involved in infection responses, raising the possibility that this gene contributes to bat antiviral defenses. These modifications in the bat innate immune system may be important adaptations allowing them to harbor viruses asymptomatically. We additionally found evidence of positive selection on the branch leading to the MRCA of bats acting on 33 tumor suppressors and six DNA repair genes, which may contribute to the low cancer rates and longevity observed across bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.Competing Interest StatementThe authors have declared no competing interest.