Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

Jebb, D.; Huang, Z.; Pippel, M.; Hughes, G. M.; Lavrichenko, K.; Devanna, P.; Winkler, S.; Jermiin, L. S.; Skirmuntt, E. C.; Katzourakis, A.; Burkitt-Gray, L.; Ray, D. A.; Sullivan, K. A.; Roscito, J. G.; Kirilenko, B. M.; Davalos, L. M.; Corthals, A. P.; Power, M.; Jones, G.; Ransome, R. D.; Dechmann, D.; Locatelli, A. G.; Puechmaille, S. J.; Fedrigo, O.; Jarvis, E. D.; Springer, M. S.; Hiller, M.; Vernes, S. C.; Myers, E. W.; Teeling, E. C.

doi:10.1101/836874

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bioRxiv · 10.1101/836874

Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

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Abstract

Bats account for ~20% of all extant mammal species and are considered exceptional given their extraordinary adaptations, including biosonar, true flight, extreme longevity, and unparalleled immune systems. To understand these adaptations, we generated reference-quality genomes of six species representing the key divergent lineages. We assembled these genomes with a novel pipeline incorporating state-of-the-art long-read and long-range sequencing and assembly techniques. The genomes were annotated using a maximal evidence approach, de novo predictions, protein/mRNA alignments, Iso-seq long read and RNA-seq short read transcripts, and gene projections from our new TOGA pipeline, retrieving virtually all (>99%) mammalian BUSCO genes. Phylogenetic analyses of 12,931 protein coding-genes and 10,857 conserved non-coding elements identified across 48 mammalian genomes helped to resolve bats closest extant relatives within Laurasiatheria, supporting a basal position for bats within Scrotifera. Genome-wide screens along the bat ancestral branch revealed (a) selection on hearing-involved genes (e.g LRP2, SERPINB6, TJP2), which suggest that laryngeal echolocation is a shared ancestral trait of bats; (b) selection (e.g INAVA, CXCL13, NPSR1) and loss of immunity related proteins (e.g. LRRC70, IL36G), including pro-inflammatory NF-kB signalling; and (c) expansion of the APOBEC family, associated with restricting viral infection, transposon activity and interferon signalling. We also identified unique integrated viruses, indicating that bats have a history of tolerating viral pathogens, lethal to other mammal species. Non-coding RNA analyses identified variant and novel microRNAs, revealing regulatory relationships that may contribute to phenotypic diversity in bats. Together, our reference-quality genomes, high-quality annotations, genome-wide screens and in-vitro tests revealed previously unknown genomic adaptations in bats that may explain their extraordinary traits.

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Jebb, D., Huang, Z., Pippel, M., Hughes, G. M., Lavrichenko, K., Devanna, P., Winkler, S., Jermiin, L. S., Skirmuntt, E. C., Katzourakis, A., Burkitt-Gray, L., Ray, D. A., Sullivan, K. A., Roscito, J. G., Kirilenko, B. M., Davalos, L. M., Corthals, A. P., Power, M., Jones, G., Ransome, R. D., Dechmann, D., Locatelli, A. G., Puechmaille, S. J., Fedrigo, O., Jarvis, E. D., Springer, M. S., Hiller, M., Vernes, S. C., Myers, E. W., Teeling, E. C.. 2019-11-09. Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations. https://doi.org/10.1101/836874

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