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

Abstract

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 assembly pipeline to generate a reference-quality genome of the fruit bat Cynopterus sphinx and used this in comparative 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.

Antiviral effects of interferon-stimulated genes in bats

“…An example in one species shows that many immune-related genes in R. aegyptiacus have undergone positive selection compared to humans, including MX1, OAS1, and ISG15 (Pavlovich et al, 2018). Similar trends have been observed for whole branches of the bat phylogenetic tree (Tian et al, 2023).…”

Spatial and single-cell transcriptomics illuminate bat immunity and barrier tissue evolution

“…We found that in contrast to the to the majority of innate immune genes that do not significantly differ in steady-state expression between the species in either lung or gut cells, many complement system genes are uniquely expressed in bat epithelial cells from both tissues. Interestingly, recent evolutionary analyses comparing bat genes with orthologs in other mammals found evidence for lineage-specific adaptation in coding sequences of bat complement system genes [66][67][68] . In agreement with this, we found that a significant fraction of the complement system genes also show elevated evolutionary rates and signatures of positive selection in their coding sequences when compared across bat species.…”

Advances in understanding bat infection dynamics across biological scales

“…Additionally, the blood proteome contains proteins secreted from blood cells and organs, including those involved in host response to infection and immune biomarkers, and innovative proteomic tools show potential in characterizing bat immune systems and their responses to microbial infections [ 45 ]. Complemented by recent advances in genomics [ 46 ], ‘-omics’ approaches stand to further our ability to explore mechanisms by which bats interact with microbes and consequences for bat physiological status.…”