Comparative analyses of bat genomes identify distinct evolution of immunity in Old World fruit bats

Bats have been identified as natural reservoir hosts of several zoonotic viruses, prompting suggestions that they have unique immunological adaptations. Among bats, Old World fruit bats (Pteropodidae) have been linked to multiple spillovers. To test for lineage-specific molecular adaptations in these bats, we developed a new assem -bly pipeline to generate a reference-quality genome of the fruit bat Cynopterus sphinx and used this in compar-ative analyses of 12 bat species, including six pteropodids. Our results reveal that immunity-related genes have higher evolutionary rates in pteropodids than in other bats. Several lineage-specific genetic changes were shared across pteropodids, including the loss of NLRP1, duplications of PGLYRP1 and C5AR2, and amino acid replacements in MyD88. We introduced MyD88 transgenes containing Pteropodidae-specific residues into bat and human cell lines and found evidence of dampened inflammatory responses. By uncovering distinct immune adaptations, our results could help explain why pteropodids are frequently identified as viral hosts.

Automated summary

Bats, especially fruit bats, have unique immunological adaptations that may explain their role as natural hosts of zoonotic viruses. Comparative analysis of 12 bat species, including six fruit bats, reveals that the evolutionary rates of immunity-related genes are higher in fruit bats. These bats share lineage-specific genetic changes in immune-related genes, resulting in dampened inflammatory responses. These findings shed light on why fruit bats are frequently identified as viral hosts.