Abstract

Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols1 to generate, to our knowledge, the first reference-quality genomes of six bat species (Rhinolophus ferrumequinum, Rousettus aegyptiacus, Phyllostomus discolor, Myotis myotis, Pipistrellus kuhlii and Molossus molossus). We integrated gene projections from our ‘Tool to infer Orthologs from Genome Alignments’ (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease1.

Highlights

  • Account for about 20% of all extant mammal species

  • For all six bat species, this resulted in assemblies with high contiguity: 96–99% of each assembly is in chromosome-level scaffolds (N50 values of 92–171.1 Mb) (Fig. 1b, Extended Data Figs. 1c, d, 2a)

  • Analysis of 197 nonexonic ultraconserved elements[20] indicates a high completeness of nonexonic genomic regions. This analysis revealed three cases of marked sequence divergence of ultraconserved elements in vespertilionid bats—something rarely observed in these elements, which are highly constrained amongst placental mammals (Extended Data Fig. 2b–d, Supplementary Figs. 1–3, Supplementary Table 5, Supplementary Note 3.2)

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Summary

Conclusion

We have generated chromosome-level, near-complete assemblies of six bat species that represent diverse chiropteran lineages. Our conservative genome-wide screens investigating gene gain, loss and selection revealed novel candidate genes that are likely to contribute tolerance to viral infections among bats. Changes in these important regulators of gene expression may have contributed to changes in developmental and behavioural processes in bats These high-quality bat genomes, together with future genomes, will provide a rich resource to address the evolutionary history and genomic basis of bat adaptations and biology, which is the ultimate goal of Bat1K1. G. et al Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. V. et al A genomics approach reveals insights into the importance of gene losses for mammalian adaptations. A. Evolutionary maintenance of filovirus-like genes in bat genomes. The evolution of endogenous retroviral envelope genes in bats and their potential contribution to host biology. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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