Abstract
One of the greatest unresolved questions in aging biology is determining the genetic basis of interspecies longevity variation. Gene duplication is often the key to understanding the origin and evolution of important Eutherian phenotypes. We systematically identified longevity-associated genes in model organisms that duplicated throughout Eutherian evolution. Longevity-associated gene families have a marginally significantly higher rate of duplication compared to non-longevity-associated gene families. Anti-longevity-associated gene families have significantly increased rate of duplication compared to pro-longevity gene families and are enriched in neurodegenerative disease categories. Conversely, duplicated pro-longevity-associated gene families are enriched in cell cycle genes. There is a cluster of longevity-associated gene families that expanded solely in long-lived species that is significantly enriched in pathways relating to 3-UTR-mediated translational regulation, metabolism of proteins and gene expression, pathways that have the potential to affect longevity. The identification of a gene cluster that duplicated solely in long-lived species involved in such fundamental processes provides a promising avenue for further exploration of Eutherian longevity evolution.