ArticleScience (New York, N.Y.)2023
Evolutionary constraint and innovation across hundreds of placental mammals.
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Article in Science (New York, N.Y.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers.
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178citing papers in PubMed
199.5field-weighted citation impact, top 1% of its field
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178 citing papers in PubMed, 249 citations in OpenAlex.
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- Evolutionary transfer learning enables organism-wide inference of mammalian enhancer landscapes.bioRxiv : the preprint server for biology · 2026Article
118 more citing papers are in PubMed but not listed here.
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Authors and funding
77 authors at 20 institutions in 7 countries.
Matthew J Christmas *Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0002-6355-7581
Irene M Kaplow *Department of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-8924-8269
Diane P GenereuxBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0001-5770-0989
Michael X DongDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0003-4084-3099
Graham M HughesSchool of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.ORCID 0000-0003-3088-345X
Xue LiBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-9126-2692
Patrick F SullivanDepartment of Genetics, University of North Carolina Medical School, Chapel Hill, NC 27599, USA.ORCID 0000-0002-6619-873X
Allyson G HindleSchool of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA.ORCID 0000-0002-1983-9573
Gregory AndrewsProgram in Bioinformatics and Integrative Biology, UMass Chan Medical School, Worcester, MA 01605, USA.ORCID 0000-0002-9880-3965
Joel C ArmstrongGenomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA.
Matteo BianchiDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0003-3394-6495
Ana M BreitSchool of Biology and Ecology, University of Maine, Orono, ME 04469, USA.ORCID 0000-0002-4990-3353
Mark DiekhansGenomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA.ORCID 0000-0002-0430-0989
Cornelia FanterSchool of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV 89154, USA.ORCID 0000-0002-4591-1866
Nicole M FoleyVeterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0002-8169-9436
Daniel B GoodmanDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0003-3759-6883
Linda GoodmanFauna Bio, Inc., Emeryville, CA 94608, USA.ORCID 0000-0002-7830-5897
Kathleen C KeoughFauna Bio, Inc., Emeryville, CA 94608, USA.ORCID 0000-0002-7481-0511
Bogdan KirilenkoFaculty of Biosciences, Goethe-University, 60438 Frankfurt, Germany.ORCID 0000-0002-9394-4275
Amanda KowalczykDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-9061-1336
Colleen LawlessSchool of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.ORCID 0000-0002-4454-7994
Abigail L LindDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-9579-4178
Jennifer R S MeadowsDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0002-0850-230X
Lucas R MoreiraBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-9084-3954
Ruby W RedlichDepartment of Biological Sciences, Mellon College of Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Louise RyanSchool of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.ORCID 0000-0002-6876-677X
Ross SwoffordBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0003-3676-8479
Alejandro ValenzuelaDepartment of Experimental and Health Sciences, Institute of Evolutionary Biology (UPF-CSIC), Universitat Pompeu Fabra, 08003 Barcelona, Spain.ORCID 0000-0002-2252-3887
Franziska WagnerMuseum of Zoology, Senckenberg Natural History Collections Dresden, 01109 Dresden, Germany.
Ola WallermanDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0003-1037-7904
Ashley R BrownDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-3091-3930
Joana DamasThe Genome Center, University of California Davis, Davis, CA 95616, USA.ORCID 0000-0003-4857-2510
Kaili FanProgram in Bioinformatics and Integrative Biology, UMass Chan Medical School, Worcester, MA 01605, USA.ORCID 0000-0002-8723-7902
John GatesyDivision of Vertebrate Zoology, American Museum of Natural History, New York, NY 10024, USA.ORCID 0000-0003-3061-7741
Jenna GrimshawDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.ORCID 0000-0001-7673-5167
Jeremy JohnsonBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0001-8548-5972
Sergey V KozyrevDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0001-6209-4100
Alyssa J LawlerNeuroscience Institute, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-2151-5164
Voichita D MarinescuDepartment of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0002-4803-4707
Kathleen M MorrillBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-9139-453X
Austin OsmanskiMedical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.ORCID 0000-0002-1485-6446
Nicole S PaulatDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.ORCID 0000-0002-6881-2588
BaDoi N PhanDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0001-6331-5980
Steven K ReillyDepartment of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0003-3140-1483
Daniel E SchäfferDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0003-3608-152X
Cynthia SteinerConservation Genetics, San Diego Zoo Wildlife Alliance, Escondido, CA 92027, USA.ORCID 0000-0002-2131-8072
Megan A SuppleDepartment of Ecology and Evolutionary Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA.ORCID 0000-0002-0204-7852
Aryn P WilderConservation Genetics, San Diego Zoo Wildlife Alliance, Escondido, CA 92027, USA.ORCID 0000-0003-4970-6891
Morgan E WirthlinDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0001-7967-7070
James R XueBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-3332-5747
Zoonomia Consortium§
Bruce W BirrenBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Steven GazalKeck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.ORCID 0000-0003-4510-5730
Robert M HubleyInstitute for Systems Biology, Seattle, WA 98109, USA.ORCID 0000-0001-9261-3821
Klaus-Peter KoepfliCenter for Species Survival, Smithsonian's National Zoo and Conservation Biology Institute, Washington, DC 20008, USA.
Tomas Marques-BonetCatalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.ORCID 0000-0002-5597-3075
Wynn K MeyerDepartment of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA.ORCID 0000-0001-7978-3877
Martin NweeiaDepartment of Comprehensive Care, School of Dental Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.ORCID 0000-0001-7079-4123
Pardis C SabetiBroad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-9843-1890
Beth ShapiroDepartment of Ecology and Evolutionary Biology, University of California Santa Cruz, Santa Cruz, CA 95064, USA.ORCID 0000-0002-2733-7776
Arian F A SmitInstitute for Systems Biology, Seattle, WA 98109, USA.ORCID 0000-0003-2088-3165
Mark S SpringerDepartment of Evolution, Ecology and Organismal Biology, University of California Riverside, Riverside, CA 92521, USA.ORCID 0000-0001-7335-6946
Emma C TeelingSchool of Biology and Environmental Science, University College Dublin, Belfield, Dublin 4, Ireland.ORCID 0000-0002-3309-1346
Zhiping WengProgram in Bioinformatics and Integrative Biology, UMass Chan Medical School, Worcester, MA 01605, USA.ORCID 0000-0002-3032-7966
Michael HillerFaculty of Biosciences, Goethe-University, 60438 Frankfurt, Germany.ORCID 0000-0003-3024-1449
Danielle L LevesqueSchool of Biology and Ecology, University of Maine, Orono, ME 04469, USA.ORCID 0000-0003-0132-8094
Harris A LewinThe Genome Center, University of California Davis, Davis, CA 95616, USA.ORCID 0000-0002-1043-7287
William J MurphyVeterinary Integrative Biosciences, Texas A&M University, College Station, TX 77843, USA.ORCID 0000-0003-3699-0723
Arcadi NavarroCatalan Institution of Research and Advanced Studies (ICREA), 08010 Barcelona, Spain.ORCID 0000-0003-2162-8246
Benedict PatenGenomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA.ORCID 0000-0001-8863-3539
Katherine S PollardDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-9870-6196
David A RayDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USA.ORCID 0000-0002-3340-3987
Irina RufDivision of Messel Research and Mammalogy, Senckenberg Research Institute and Natural History Museum Frankfurt, 60325 Frankfurt am Main, Germany.ORCID 0000-0002-9728-1210
Oliver A RyderConservation Genetics, San Diego Zoo Wildlife Alliance, Escondido, CA 92027, USA.ORCID 0000-0003-2427-763X
Andreas R PfenningDepartment of Computational Biology, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.ORCID 0000-0002-3447-9801
Kerstin Lindblad-Toh *Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, 751 32 Uppsala, Sweden.ORCID 0000-0001-8338-0253
Elinor K Karlsson *Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.ORCID 0000-0002-4343-3776
Broad Institute · USUppsala University · SEUniversity College Dublin · IECarnegie Mellon University · USTexas Tech University · USUniversity of California, Santa Cruz · USGladstone Institutes · USUniversity of Massachusetts Chan Medical School · USZoological Society of San Diego · USInstitució Catalana de Recerca i Estudis Avançats · ESGoethe University Frankfurt · DETexas A&M University · USUniversity of Maine · USUniversity of Nevada, Las Vegas · USUniversity of North Carolina at Chapel Hill · USUniversity of Pittsburgh · USHoward Hughes Medical Institute · USInstitute for Systems Biology · USJohn Muir Health · USUniversitat Pompeu Fabra · ES
Funding
The UCSC Genome BrowserU41HG002371 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI KENT, WILLIAM JAMES · 2012 to 2021
$36.6MThe Dog Aging Project: Genetic and Environmental Determinants of Healthy Aging in Companion Dogs Competitive RevisionU19AG057377 · NIA · UNIVERSITY OF WASHINGTON · PI KEENE, CHRISTOPHER DIRK, PROMISLOW, DANIEL EDWARD · 2018 to 2023
$29.0MGENCODE Resource ProjectU41HG007234 · NHGRI · SANGER INSTITUTE · PI FLICEK, PAUL · 2013 to 2020
$20.3MGENCODE: comprehensive reference genome annotation for human and mouseU24HG007234 · NHGRI · EUROPEAN MOLECULAR BIOLOGY LABORATORY · PI Fergal James Martin · 2021 to 2026
$16.1MEDAC: ENCODE Data Analysis CenterU24HG009446 · NHGRI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI GERSTEIN, MARK BENDER, WENG, ZHIPING · 2017 to 2022
$10.4MMaintenance and Development of RepeatMasker and RepeatModelerR01HG002939 · NHGRI · INSTITUTE FOR SYSTEMS BIOLOGY · PI Robert MacDonald Hubley, Arian Fredericus Anthonius Smit · 2003 to 2026
$9.1MDfam: sustainable growth, curation support, and improved quality for mobile element annotationU24HG010136 · NHGRI · INSTITUTE FOR SYSTEMS BIOLOGY · PI Robert MacDonald Hubley, Arian Fredericus Anthonius Smit · 2018 to 2026
$5.2MTransforming family dogs into a powerful and accessible model for human cancerR37CA218570 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KARLSSON, ELINOR · 2018 to 2022
$3.2MThe construction and utility of reference pan-genome graphsU01HG010961 · NHGRI · DANA-FARBER CANCER INST · PI LI, HENG, PATEN, BENEDICT · 2020 to 2023
$3.2MLeveraging canine spontaneous cancer to optimize the power of blood biopsyR01CA255319 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI KARLSSON, ELINOR, LONDON, CHERYL A · 2021 to 2025
$3.1MThe 200 mammals project: sequencing genomes by a novel cost-effective method, yielding a high resolution annotation of the human genome.R01HG008742 · NHGRI · BROAD INSTITUTE, INC. · PI BIRREN, BRUCE W., KARLSSON, ELINOR · 2016 to 2020
$2.8MEnabling Comparative PangenomicsR01HG010485 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI HAUSSLER, DAVID H, MARTIN, FERGAL JAMES · 2020 to 2023
$2.6MNCI NIH HHS R01 CA255319NCI NIH HHS R37 CA218570NHGRI NIH HHS R01 HG002939NHGRI NIH HHS R01 HG008742NHGRI NIH HHS R01 HG010485NHGRI NIH HHS U01 HG010961NHGRI NIH HHS U24 HG007234NHGRI NIH HHS U24 HG009446NHGRI NIH HHS U24 HG010136NHGRI NIH HHS U41 HG002371NHGRI NIH HHS U41 HG007234NIA NIH HHS U19 AG057377NIDA NIH HHS DP1 DA046585NIDA NIH HHS F30 DA053020NIH HHS R24 OD018250
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.
Indexed as
EutheriaEvolution, MolecularAnimalsConserved SequenceFemaleGenome, HumanHumans
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