IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v478y2011i7370d10.1038_nature10530.html
   My bibliography  Save this article

A high-resolution map of human evolutionary constraint using 29 mammals

Author

Listed:
  • Kerstin Lindblad-Toh

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    Science for Life Laboratory, Uppsala University, Box 582)

  • Manuel Garber

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Or Zuk

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Michael F. Lin

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Brian J. Parker

    (The Bioinformatics Centre, University of Copenhagen)

  • Stefan Washietl

    (MIT Computer Science and Artificial Intelligence Laboratory)

  • Pouya Kheradpour

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Jason Ernst

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Gregory Jordan

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Evan Mauceli

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Lucas D. Ward

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    MIT Computer Science and Artificial Intelligence Laboratory)

  • Craig B. Lowe

    (Center for Biomolecular Science and Engineering, University of California
    Stanford University
    Howard Hughes Medical Institute, 4000 Jones Bridge Road)

  • Alisha K. Holloway

    (Gladstone Institutes, University of California)

  • Michele Clamp

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    BioTeam Inc, 7 Derosier Drive)

  • Sante Gnerre

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Jessica Alföldi

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Kathryn Beal

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Jean Chang

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Hiram Clawson

    (Center for Biomolecular Science and Engineering, University of California)

  • James Cuff

    (Research Computing, Faculty of Arts and Sciences, Harvard University)

  • Federica Di Palma

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Stephen Fitzgerald

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Paul Flicek

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Mitchell Guttman

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Melissa J. Hubisz

    (Cornell University)

  • David B. Jaffe

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Irwin Jungreis

    (MIT Computer Science and Artificial Intelligence Laboratory)

  • W. James Kent

    (Gladstone Institutes, University of California)

  • Dennis Kostka

    (Gladstone Institutes, University of California)

  • Marcia Lara

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Andre L. Martins

    (Cornell University)

  • Tim Massingham

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Ida Moltke

    (The Bioinformatics Centre, University of Copenhagen)

  • Brian J. Raney

    (Center for Biomolecular Science and Engineering, University of California)

  • Matthew D. Rasmussen

    (MIT Computer Science and Artificial Intelligence Laboratory)

  • Jim Robinson

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Alexander Stark

    (Research Institute of Molecular Pathology (IMP))

  • Albert J. Vilella

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Jiayu Wen

    (The Bioinformatics Centre, University of Copenhagen)

  • Xiaohui Xie

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Michael C. Zody

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Kim C. Worley

    (Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza)

  • Christie L. Kovar

    (Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza)

  • Donna M. Muzny

    (Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza)

  • Richard A. Gibbs

    (Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza)

  • Wesley C. Warren

    (Genome Institute at Washington University, Washington University School of Medicine)

  • Elaine R. Mardis

    (Genome Institute at Washington University, Washington University School of Medicine)

  • George M. Weinstock

    (Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza
    Genome Institute at Washington University, Washington University School of Medicine)

  • Richard K. Wilson

    (Genome Institute at Washington University, Washington University School of Medicine)

  • Ewan Birney

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Elliott H. Margulies

    (Genome Informatics Section, Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health)

  • Javier Herrero

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Eric D. Green

    (NISC Comparative Sequencing Program, Genome Technology Branch and NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health)

  • David Haussler

    (Center for Biomolecular Science and Engineering, University of California
    Howard Hughes Medical Institute, 4000 Jones Bridge Road)

  • Adam Siepel

    (Cornell University)

  • Nick Goldman

    (EMBL-EBI, Wellcome Trust Genome Campus)

  • Katherine S. Pollard

    (Gladstone Institutes, University of California
    Institute for Human Genetics, University of California)

  • Jakob S. Pedersen

    (The Bioinformatics Centre, University of Copenhagen
    Aarhus University Hospital, Skejby)

  • Eric S. Lander

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center)

  • Manolis Kellis

    (Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 7 Cambridge Center
    MIT Computer Science and Artificial Intelligence Laboratory)

Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.

Suggested Citation

  • Kerstin Lindblad-Toh & Manuel Garber & Or Zuk & Michael F. Lin & Brian J. Parker & Stefan Washietl & Pouya Kheradpour & Jason Ernst & Gregory Jordan & Evan Mauceli & Lucas D. Ward & Craig B. Lowe & Al, 2011. "A high-resolution map of human evolutionary constraint using 29 mammals," Nature, Nature, vol. 478(7370), pages 476-482, October.
    • Handle: RePEc:nat:nature:v:478:y:2011:i:7370:d:10.1038_nature10530
    DOI: 10.1038/nature10530
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature10530
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature10530?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Lijing Tang & Benjamin Swedlund & Sébastien Dupont & Chad Harland & Gabriel Costa Monteiro Moreira & Keith Durkin & Maria Artesi & Eric Mullaart & Arnaud Sartelet & Latifa Karim & Wouter Coppieters & , 2024. "GWAS reveals determinants of mobilization rate and dynamics of an active endogenous retrovirus of cattle," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Adriana Arneson & Amin Haghani & Michael J. Thompson & Matteo Pellegrini & Soo Bin Kwon & Ha Vu & Emily Maciejewski & Mingjia Yao & Caesar Z. Li & Ake T. Lu & Marco Morselli & Liudmilla Rubbi & Bret B, 2022. "A mammalian methylation array for profiling methylation levels at conserved sequences," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Scott D. Findlay & Lindsay Romo & Christopher B. Burge, 2024. "Quantifying negative selection in human 3ʹ UTRs uncovers constrained targets of RNA-binding proteins," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Maria Niarchou & Daniel E. Gustavson & J. Fah Sathirapongsasuti & Manuel Anglada-Tort & Else Eising & Eamonn Bell & Evonne McArthur & Peter Straub & J. Devin McAuley & John A. Capra & Fredrik Ullén & , 2022. "Genome-wide association study of musical beat synchronization demonstrates high polygenicity," Nature Human Behaviour, Nature, vol. 6(9), pages 1292-1309, September.
    5. Xinru Zhang & Bohao Fang & Yi-Fei Huang, 2023. "Transcription factor binding sites are frequently under accelerated evolution in primates," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Alan Selewa & Kaixuan Luo & Michael Wasney & Linsin Smith & Xiaotong Sun & Chenwei Tang & Heather Eckart & Ivan P. Moskowitz & Anindita Basu & Xin He & Sebastian Pott, 2023. "Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:478:y:2011:i:7370:d:10.1038_nature10530. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.