Convergent evolution of longevity reveals divergent genomic mechanisms in small and large mammals

Extended lifespan has evolved repeatedly across mammals, yet the molecular mechanisms underlying this convergent trait remain poorly understood. Although maximum lifespan is correlated with body size, exceptional longevity has evolved at both ends of the mammalian size spectrum, occurring in small, long-lived mammals such as bats and mole-rats and in large, long-lived mammals such as whales and elephants. It remains unclear whether these distinct mammalian size groups achieve longevity through shared molecular pathways or lineage-specific adaptations. Here, we perform an integrated comparative genomic and transcriptomic analysis to test the hypothesis that Extremely Long-Lived Small Mammals (ELLSM) and Body-Mass-Associated Long-Lived Mammals (BMAL) exhibit distinct molecular signatures of longevity. Our analyses reveal that longevity is driven by intensified natural selection in ELLSM, consistent with the need for enhanced cellular maintenance to offset the high metabolic costs of small body size. In contrast, BMAL lineages show a genome-wide pattern of relaxed selection yet retain strong sequence-level constraint on pathways controlling cell cycle and DNA repair. Transcriptomic profiles reveal a complementary divergence, with BMAL signatures emphasizing cell cycle regulation and growth, and ELLSM signatures overwhelmingly enriched for transcriptional upregulation of DNA repair and autophagy. Despite sharing the phenotype of extended lifespan, we find minimal overlap in the specific genes and pathways under selection between the two groups. BMAL longevity is tied to stringent control of cell proliferation that suppresses cancer, whereas ELLSM longevity is tied to enhanced cellular maintenance and repair that preserves long-term cell function. Taken together, our findings indicate that mammalian longevity is a convergent phenotype achieved through divergent evolutionary strategies.