Christmas, Matthew J.Valenzuela, AlejandroMarquès i Bonet, Tomàs, 1975-Navarro i Cuartiellas, Arcadi, 1969-Karlsson, Elinor K.2024-03-272024-03-272023Christmas MJ, Kaplow IM, Genereux DP, Dong MX, Hughes GM, Li X, et al. Evolutionary constraint and innovation across hundreds of placental mammals. Science. 2023 Apr 28;380(6643):eabn3943. DOI: 10.1126/science.abn39430036-8075http://hdl.handle.net/10230/59591Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.application/pdfengThis is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on 2023 Apr 28;380(6643):eabn3943, DOI: 10.1126/science.abn3943.Genòmica comparativainfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/science.abn3943info:eu-repo/semantics/openAccess