Giant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases. However, genomic and molecular evolutionary information on giant tortoises is scarce. Here, we describe a global analysis of the genomes of Lonesome George-the iconic last member of Chelonoidis abingdonii-and the Aldabra giant tortoise (Aldabrachelys gigantea). Comparison of these genomes with those of related species, using both unsupervised and supervised analyses, led us to detect lineage-specific variants affecting DNA repair genes, inflammatory mediators and genes related to cancer development. Our study also hints at specific evolutionary strategies linked to increased lifespan, and expands our understanding of the genomic determinants of ageing. These new genome sequences also provide important resources to help the efforts for restoration of giant tortoise populations.

We thank Banco Santander for funding a short stay of S.F.-R. and D.C.-I. at Yale University. V.Q. is supported by grants from the Principado de Asturias and Ministerio de Economía y Competitividad, including FEDER funding. L.F.K.K. is supported by an FPI fellowship associated with BFU2014-55090-P (FEDER). T.M.-B. is supported by MINECO BFU2017-86471-P (MINECO/FEDER, UE), an NIH U01 MH106874 grant, the Howard Hughes International Early Career programme, Obra Social ‘La Caixa’ and Secretaria d’Universitats i Recerca, and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya. C.L.-O. is supported by grants from the European Research Council (DeAge; ERC Advanced Grant), Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (RTICC) and Progeria Research Foundation.