Uncovering genes contributing to exceptional longevity and immunity in bats by comparative genomic analysis across all bat families

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Bats are the only mammals that evolved powered flight and exhibit traits that are rarely found in other mammals. Bats live on average three-times longer than non-flying mammals after correcting for body size and they rarely get cancer. Infections with viruses that are deadly for humans is often asymptomatic in bats, because their immune system is able to efficiently dampen inflammatory immune responses. Thus, bats are important models for healthy aging and enhanced resistance to tumorigenesis and infectious diseases, which is relevant for human senescence, cancer, and inflammation-related disorders. However, the molecular mechanisms underlying their exceptional longevity and unique immunity remain elusive.To provide novel insights into the genes that are involved in exceptional longevity and immunity of bats, we will conduct a comprehensive comparative analysis of high-quality genomes of all 21 recognized bat families. To this end, we will generate gene annotations for representative species of all 21 families using a maximum evidence approach that integrates homology-based, de novo and transcriptome-based gene predictions. To reveal genes that likely contribute to longevity and immunity, we will systematically uncover genes that exhibit mutational loss- or gain-of-function signatures in bats. Specifically, building on established comparative genomics approaches, we will screen for ancestral genes that are inactivated in bats, genes that evolved under relaxed or positive selection, and novel genes that arose in bats.This unprecedented genomic analysis across all bat families will provide new insights into the evolution and the genomic basis of exceptional longevity and immunity in bats and is expected to reveal promising targets for future experimental tests. The generated high-quality reference gene annotations of 21 bat families represent an important resource of long term value as they enable comparative gene annotation in hundreds of bats that will be sequenced in future.