Genetic variation between long-lived versus short-lived bats illuminates the molecular signatures of longevity

Abstract

Bats are the longest-lived mammals given their body size with majority of species exhibiting exceptional longevity. However, there are some short-lived species that do not exhibit extended lifespans. Here we conducted a comparative genomic and transcriptomic study on long-lived <i>Myotis myotis</i> (maximum lifespan = 37.1 years) and short-lived <i>Molossus molossus</i> (maximum lifespan = 5.6 years) to ascertain the genetic difference underlying their divergent longevities. Genome-wide selection tests on 12,467 single-copy genes between <i>M. myotis</i> and <i>M. molossus</i> revealed only three genes (<i>CCDC175</i>, <i>FATE1</i> and <i>MLKL</i>) that exhibited significant positive selection. Although 97.96% of 12,467 genes underwent purifying selection, we observed a significant heterogeneity in their expression patterns. Using a linear mixed model, we obtained expression of 2,086 genes that may truly represent the genetic difference between <i>M. myotis</i> and <i>M. molossus</i>. Expression analysis indicated that long-lived <i>M. myotis</i> exhibited a transcriptomic profile of enhanced DNA repair and autophagy pathways, compared to <i>M. molossus</i>. Further investigation of the longevity-associated genes suggested that long-lived <i>M. myotis</i> have naturally evolved a diminished anti-longevity transcriptomic profile. Together with observations from other long-lived species, our results suggest that heightened DNA repair and autophagy activity may represent a universal mechanism to achieve longevity in long-lived mammals.