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Natural selection on protein-coding genes in the human genome

Author

Listed:
  • Carlos D. Bustamante

    (Cornell University)

  • Adi Fledel-Alon

    (Cornell University)

  • Scott Williamson

    (Cornell University)

  • Rasmus Nielsen

    (Cornell University
    University of Copenhagen)

  • Melissa Todd Hubisz

    (Cornell University)

  • Stephen Glanowski

    (Applied Biosystems)

  • David M. Tanenbaum

    (Applied Biosystems)

  • Thomas J. White

    (Celera Diagnostics)

  • John J. Sninsky

    (Celera Diagnostics)

  • Ryan D. Hernandez

    (Cornell University)

  • Daniel Civello

    (Celera Diagnostics)

  • Mark D. Adams

    (Case Western Reserve University)

  • Michele Cargill

    (Celera Diagnostics)

  • Andrew G. Clark

    (Cornell University)

Abstract

Go forth and evolve Are we still evolving? The simple answer is yes. A comparison of the sequences of over 11,000 genes from 39 human individuals and from chimpanzees reveals more than 1,139 genes that show evidence of either positive or weak negative selection. Certain gene types (such as transcription factors) show an excess of rapidly evolving genes and others (such as cytoskeletal proteins) show an excess of genes subject to weak negative selection. Genes associated with human disease tend to show a signature of past selection: this may be because complex common diseases are most likely to arise from genes that can tolerate mildly deleterious variation. Mutations that grossly affect gene function are likely to be kept at low frequencies by natural selection and thus contribute little to explaining variation in common disease.

Suggested Citation

  • Carlos D. Bustamante & Adi Fledel-Alon & Scott Williamson & Rasmus Nielsen & Melissa Todd Hubisz & Stephen Glanowski & David M. Tanenbaum & Thomas J. White & John J. Sninsky & Ryan D. Hernandez & Dani, 2005. "Natural selection on protein-coding genes in the human genome," Nature, Nature, vol. 437(7062), pages 1153-1157, October.
    • Handle: RePEc:nat:nature:v:437:y:2005:i:7062:d:10.1038_nature04240
    DOI: 10.1038/nature04240
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    Cited by:

    1. Julian Petersen & Lukas Englmaier & Artem V. Artemov & Irina Poverennaya & Ruba Mahmoud & Thibault Bouderlique & Marketa Tesarova & Ruslan Deviatiiarov & Anett Szilvásy-Szabó & Evgeny E. Akkuratov & D, 2023. "A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Xiaoyu Tu & Sibo Ren & Wei Shen & Jianjian Li & Yuxiang Li & Chuanshun Li & Yangmeihui Li & Zhanxiang Zong & Weibo Xie & Donald Grierson & Zhangjun Fei & Jim Giovannoni & Pinghua Li & Silin Zhong, 2022. "Limited conservation in cross-species comparison of GLK transcription factor binding suggested wide-spread cistrome divergence," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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