Evolutionary constraint and innovation across hundreds of placental mammals

著者: Matthew J. Christmas, Irene M. Kaplow, Diane P. Genereux, Michael X. Dong, Graham M. Hughes, Xue Li, Patrick F. Sullivan, Allyson G. Hindle, Gregory Andrews, Joel C. Armstrong, Matteo Bianchi, Ana M. Breit, Mark Diekhans, Cornelia Fanter, Nicole M. Foley, Daniel B. Goodman, Linda Goodman, Kathleen C. Keough, Bogdan Kirilenko, Amanda Kowalczyk, Colleen Lawless, Abigail Lind, Jennifer R. S. Meadows, Lucas R. Moreira, Ruby Redlich, Louise Ryan, Ross Swofford, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Ashley R. Brown, Joana Damas, Kaili Fan, John Gatesy, Jenna Grimshaw, Jeremy Johnson, Sergey V. Kozyrev, Alyssa J. Lawler, Voichita D. Marinescu, Kathleen M. Morrill, Austin Osmanski, Nicole S. Paulat, BaDoi N. Phan, Steven K. Reilly, Daniel E. Schäffer, Cynthia Steiner, Megan A. Supple, Aryn P. Wilder, Morgan Wirthlin, James R. Xue, Susan J. Birren, Steven Gazal, Robert M. Hubley, Klaus-Peter Koepfli, Tomàs Marquès‐Bonet, Wynn K. Meyer, Martin Nweeia, Pardis C. Sabeti, Beth Shapiro, Arian F. A. Smit, Mark S. Springer, Emma C. Teeling, Zhiping Weng, Michael Hiller, Danielle L. Levesque, Harris A. Lewin, William J. Murphy, Arcadi Navarro, Benedict Paten, Katherine S. Pollard, David A. Ray, Irina Ruf, Oliver A. Ryder, Andreas R. Pfenning, Kerstin Lindblad‐Toh, Elinor K. Karlsson, Gregory Andrews, Joel C. Armstrong, Matteo Bianchi, Susan J. Birren, Kevin R. Bredemeyer, Ana M. Breit, Matthew J. Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X. Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M. Foley, Karin Forsberg‐Nilsson, Carlos J. Garcia, John Gatesy, Steven Gazal, Diane P. Genereux, Linda Goodman, Jenna Grimshaw, Michaela K. Halsey, Andrew J. Harris, Glenn Hickey, Michael Hiller, Allyson G. Hindle, Robert M. Hubley, Graham M. Hughes, Jeremy Johnson, David Juan, Irene M. Kaplow, Elinor K. Karlsson, Kathleen C. Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M. Korstian, Amanda Kowalczyk, Sergey V. Kozyrev, Alyssa J. Lawler, Colleen Lawless, Thomas Lehmann, Danielle L. Levesque, Harris A. Lewin, Xue Li, Abigail Lind, Kerstin Lindblad‐Toh, Ava Mackay-Smith, Voichita D. Marinescu, Tomàs Marquès‐Bonet, Victor C. Mason, Jennifer R. S. Meadows, Wynn K. Meyer, Jill E. Moore, Lucas R. Moreira, Diana D. Moreno-Santillán, Kathleen M. Morrill, Gerard Muntané, William J. Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S. Paulat, Andreas R. Pfenning, BaDoi N. Phan, Katherine S. Pollard, Henry Pratt, David A. Ray, Steven K. Reilly, Jeb Rosen, Irina Ruf, Louise Ryan, Oliver A. Ryder, Pardis C. Sabeti, Daniel E. Schäffer, Aitor Serres, Beth Shapiro, Arian F. A. Smit, Mark S. Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M. Storer, Kevin A. Sullivan, Patrick F. Sullivan, Elisabeth Sundström, Megan A. Supple, Ross Swofford, Joy-El Talbot, Emma C. Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P. Wilder, Morgan Wirthlin, James R. Xue, Xiaomeng Zhang - Science 2023 被引用: 268

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.