RT Journal Article SR Electronic T1 Concurrent evolution of anti-aging gene duplications and cellular phenotypes in long-lived turtles JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.07.07.451454 DO 10.1101/2021.07.07.451454 A1 Scott Glaberman A1 Stephanie E. Bulls A1 Juan Manuel Vazquez A1 Ylenia Chiari A1 Vincent J. Lynch YR 2021 UL http://biorxiv.org/content/early/2021/07/08/2021.07.07.451454.abstract AB There are many costs associated with increased body size and longevity in animals, including the accumulation of genotoxic and cytotoxic damage that comes with having more cells and living longer. Yet, some species have overcome these barriers and have evolved remarkably large body sizes and long lifespans, sometimes within a narrow window of evolutionary time. Here, we demonstrate through phylogenetic comparative analysis that multiple turtle lineages, including Galapagos giant tortoises, concurrently evolved large bodies, long lifespans, and reduced cancer risk. We also show through comparative genomic analysis that Galapagos giant tortoises have gene duplications related to longevity and tumor suppression. To examine the molecular basis underlying increased body size and lifespan in turtles, we treated cell lines from multiple species, including Galapagos giant tortoises, with drugs that induce different types of cytotoxic stress. Our results indicate that turtle cells, in general, are resistant to oxidative stress related to aging, while Galapagos giant tortoise cells, specifically, are sensitive to endoplasmic reticulum stress, which may give this species an ability to mitigate the effects of cellular stress associated with increased body size and longevity.Competing Interest StatementThe authors have declared no competing interest.