Large‐scale genome sampling reveals unique immunity and metabolic adaptations in bats

Comprising more than 1,400 species, bats possess adaptations unique among
mammals including powered flight, unexpected longevity given small body
size, and extraordinary immunity. Some of the molecular mechanisms
underlying these unique adaptations includes DNA repair, metabolism and
immunity. However, analyses have been limited to a few divergent lineages,
reducing the scope of inferences on gene family evolution across the Order
Chiroptera. We conducted an exhaustive comparative genomic study of 37 bat
species encompassing a large number of lineages, with a particular
emphasis on multi-gene family evolution across immune system and metabolic
genes. Genomes were obtained from public repositories and one genome
(Phyllostomus hastatus) was assembled de novo. In agreement with previous
analyses, we found lineage-specific expansions of the APOBEC3 and MHC-I
gene families, and loss of the proinflammatory PYHIN gene family. We
inferred more than 1,000 gene losses unique to bats, including genes
involved in the regulation of inflammasome pathways such as epithelial
defense receptors, the natural killer gene complex and the
interferon-gamma induced pathway. Gene set enrichment analyses revealed
genes lost in bats are involved in defense response against
pathogen-associated molecular patterns and damage-associated molecular
patterns. Gene family evolution and selection analyses indicate bats have
evolved fundamental functional differences compared to other mammals in
both innate and adaptive immune system, with the potential to enhance
anti-viral immune response while dampening inflammatory signaling. In
addition, metabolic genes have experienced repeated expansions related to
convergent shifts to plant-based diets. Our analyses support the
hypothesis that, in tandem with flight, ancestral bats had evolved a
unique set of immune adaptations whose functional implications remain to
be explored.