Evolutionary constraint and innovation across hundreds of placental mammals

• 成果类型: Article
• 署名作者: Christmas, Matthew J.; Kaplow, Irene M.; Genereux, Diane P.; Dong, Michael X.; Hughes, Graham M.; Li, Xue; Sullivan, Patrick F.; Hindle, Allyson G.; Andrews, Gregory; Armstrong, Joel C.; Bianchi, Matteo; Breit, Ana M.; Diekhans, Mark; Fanter, Cornelia; Foley, Nicole M.; Goodman, Daniel B.; Goodman, Linda; Keough, Kathleen C.; Kirilenko, Bogdan; Kowalczyk, Amanda; Lawless, Colleen; Lind, Abigail L.; Meadows, Jennifer R. S.; Moreira, Lucas R.; Redlich, Ruby W.; Ryan, Louise; Swofford, Ross; Valenzuela, Alejandro; Wagner, Franziska; Wallerman, Ola; Brown, Ashley R.; Damas, Joana; Fan, Kaili; Gatesy, John; Grimshaw, Jenna; Johnson, Jeremy; Kozyrev, Sergey V.; Lawler, Alyssa J.; Marinescu, Voichita D.; Morrill, Kathleen M.; Osmanski, Austin; Paulat, Nicole S.; Phan, BaDoi N.; Reilly, Steven K.; Schaeffer, Daniel E.; Steiner, Cynthia; Supple, Megan A.; Wilder, Aryn P.; Wirthlin, Morgan E.; Xue, James R.; Birren, Bruce W.; Gazal, Steven; Hubley, Robert M.; Koepfli, Klaus-Peter; Marques-Bonet, Tomas; Meyer, Wynn K.; Nweela, Martin; Sabeti, Pardis C.; Shapiro, Beth; Smit, Arian F. A.; Springer, Mark S.; Teeling, Emma C.; Weng, Zhiping; Hiller, Michael; Levesque, Danielle L.; Lewin, Harris A.; Murphy, William J.; Navarro, Arcadi; Paten, Benedict; Pollard, Katherine S.; Ray, David A.; Ruf, Irina; Ryder, Oliver A.; Pfenning, Andreas R.; Lindblad-Toh, Kerstin; Karlsson, Elinor K.
• 署名单位: Uppsala University; Carnegie Mellon University; Carnegie Mellon University; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; University College Dublin; University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester; University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester; Karolinska Institutet; Nevada System of Higher Education (NSHE); University of Nevada Las Vegas; University of California System; University of California Santa Cruz; University of Maine System; University of Maine Orono; Texas A&M University System; Texas A&M University College Station; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; The J David Gladstone Institutes; Goethe University Frankfurt; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); Carnegie Mellon University; Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Pompeu Fabra University; Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); University of California System; University of California Davis; American Museum of Natural History (AMNH); Texas Tech University System; Texas Tech University; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Yale University; University of California System; University of California Santa Cruz; Allen Institute for Brain Science; Harvard University; University of Southern California; Institute for Systems Biology (ISB); Smithsonian Institution; Smithsonian National Zoological Park & Conservation Biology Institute; ITMO University; Smithsonian Institution; Smithsonian National Zoological Park & Conservation Biology Institute; ICREA; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Consejo Superior de Investigaciones Cientificas (CSIC); CSIC-UPF - Institut de Biologia Evolutiva (IBE); Pompeu Fabra University; Autonomous University of Barcelona; Institut Catala de Paleontologia Miquel Crusafont (ICP); Lehigh University; University System of Ohio; Case Western Reserve University; Smithsonian Institution; Smithsonian National Museum of Natural History; Harvard University; Harvard School of Dental Medicine; Harvard University; Howard Hughes Medical Institute; University of California System; University of California Santa Cruz; Howard Hughes Medical Institute; University of California System; University of California Riverside; University of California System; University of California Davis; University of California System; University of California Davis; Barcelona Institute of Science & Technology; Pompeu Fabra University; Centre de Regulacio Genomica (CRG); Chan Zuckerberg Initiative (CZI); Leibniz Association; Senckenberg Gesellschaft fur Naturforschung (SGN); University of California System; University of California San Diego; University of Massachusetts System; UMass Chan Medical School; University of Massachusetts Worcester
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10068
• DOI: 10.1126/science.abn3943
• 发表日期: 2023-04-28
• 页码: 366-+
• 关键词: conserved noncoding sequences; receptor gene repertoires; ultraconserved elements; transposable elements; human genome; vertebrate; ACID; expansion; DYNAMICS; reveals

摘要

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 (similar to 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.