Evolutionary constraint and innovation across hundreds of placental mammals

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  • dc.contributor.author Christmas, Matthew J.
  • dc.contributor.author Valenzuela, Alejandro
  • dc.contributor.author Marquès i Bonet, Tomàs, 1975-
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
  • dc.contributor.author Karlsson, Elinor K.
  • dc.date.accessioned 2024-03-27T08:13:04Z
  • dc.date.available 2024-03-27T08:13:04Z
  • dc.date.issued 2023
  • dc.description.abstract Zoonomia 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.
  • dc.description.sponsorship This work was funded by National Institutes of Health (NIH) grant R37CA218570; NIH grant R01HG008742; NIH grant R01HG010485; NIH grant RO1-HG002939; NIH grant U01HG010961; NIH grant U24-HG010136; NIH grant U24HG009446; NIH grant U41HG002371; NIH grant U41HG007234; NIH grant U19AG057377; NIH grant DP1DA046585; NIH grant F30DA053020; NIH grant R24OD018250; National Science Foundation (NSF) grant DEB-1753760; NSF grant DEB-2150664; NSF grant DBI-2046550; NSF grant DEB 1838283; NSF grant DEB-1457735; NSF grant DGE-1252522; NSF grant DGE-1745016; NSF grant IOS-2032006; NSF grant IOS-1929592; NSF grant IOS-2022007; NSF grant IOS-2029774; NSF grant TG-BIO200055; NSF grant ACI-1548562; NSF Postdoctoral Fellowship in Biology 2011038 (C.F.); European Research Council under the European Union’s Horizon 2020 research and innovation program grant 864203 (T.M.-B.); MINECO/FEDER, UE grant PID2021-126004NB-100 (T.M.-B.); FEDER/UE grant AEI-PGC2018-101927-BI00 704 (A.N.C.), AEI grant CEX2018-000792-M (A.N.C. and T.M.-B.), Science Foundation Ireland 19/FFP/6790 (E.C.T.); Irish Research Council Laureate grant (E.C.T.); Distinguished professorship from the Swedish Research Council (K.L.-T.); Swedish Research Council Vetenskapsrådet grant D0886501 (P.F.S.); Carnegie Mellon University Computational Biology Department Lane Postdoctoral Fellowship (I.M.K.); Carnegie Mellon University SURF grant (D.E.S.); Gift from Ed and Pam Taft, Roddenberry Foundation, Gladstone Institutes (K.S.P.); LOEWE-Centre for Translational Biodiversity Genomics (M.H.); Robert and Rosabel Osborne Endowment, UC Davis (H.A.L.); SFI Centre for Research Training in Genomics Data Science grant 18/CRT/6214 (L.R.); Sloan Foundation grant (A.R.P.); UMaine Institute of Medicine Seed Grant (D.L.L.); University College Dublin Ad Astra Fellowship (G.M.H.); Knut and Alice Wallenberg Foundation (K.L.-T.); NSF grant 2019035 (Lehigh University Research Computing Infrastructure); NSF grant TG-BIO200055 [The Extreme Science and Engineering Discovery Environment (XSEDE)]; and Swedish Research Council grant 2018-05973 [Swedish National Infrastructure for Computing (SNIC) at UPPMAX].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Christmas 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.abn3943
  • dc.identifier.doi http://dx.doi.org/10.1126/science.abn3943
  • dc.identifier.issn 0036-8075
  • dc.identifier.uri http://hdl.handle.net/10230/59591
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Science. 2023 Apr 28;380(6643):eabn3943
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/864203
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-126004NB-100
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PGC2018-101927-B-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2018-000792-M
  • dc.rights This 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.subject.other Genòmica comparativa
  • dc.title Evolutionary constraint and innovation across hundreds of placental mammals
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/acceptedVersion

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Articles (Departament de Medicina i Ciències de la Vida)
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