Rapid evolution of the human mutation spectrum

  1. Kelley Harris  Is a corresponding author
  2. Jonathan K Pritchard  Is a corresponding author
  1. Stanford University, United States


DNA is a remarkably precise medium for copying and storing biological information. This high fidelity results from the action of hundreds of genes involved in replication, proofreading, and damage repair. Evolutionary theory suggests that in such a system, selection has limited ability to remove genetic variants that change mutation rates by small amounts or in specific sequence contexts. Consistent with this, using SNV variation as a proxy for mutational input, we report here that mutational spectra differ substantially among species, human continental groups and even some closely-related populations. Close examination of one signal, an increased TCC-to-TTC mutation rate in Europeans, indicates a burst of mutations from about 15,000 to 2,000 years ago, perhaps due to the appearance, drift, and ultimate elimination of a genetic modifier of mutation rate. Our results suggest that mutation rates can evolve markedly over short evolutionary timescales and suggest the possibility of mapping mutational modifiers.

Data availability

The following previously published data sets were used
    1. 1000 Genomes Project Consortium
    (2015) 1000 Genomes Phase 3
    Publicly available at internationalgenome.org.
    1. Swapan Mallick
    2. David Reich
    3. et al.
    (2016) Simons Genome Diversity Project
    Directions for downloading available here: http://simonsfoundation.s3.amazonaws.com/share/SCDA/datasets/2014_11_12/StepstodownloadtheSGDPdataset_v4.docx.
    1. Monkol Lek
    2. Daniel MacArthur
    3. et al.
    (2016) Exome Aggregation Consortium
    Summary data publicly available for download at http://exac.broadinstitute.org/downloads.

Article and author information

Author details

  1. Kelley Harris

    Genetics, Stanford University, Stanford, CA, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0302-2523
  2. Jonathan K Pritchard

    Department of Genetics, Stanford University, Stanford, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.


National Institutes of Health (NRSA-F32 Grant GM116381)

  • Kelley Harris

Howard Hughes Medical Institute (Investigator Grant)

  • Jonathan K Pritchard

National Institutes of Health (R01 Grant HG008140)

  • Jonathan K Pritchard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gilean McVean, Oxford University, United Kingdom

Publication history

  1. Received: December 15, 2016
  2. Accepted: April 7, 2017
  3. Accepted Manuscript published: April 25, 2017 (version 1)
  4. Version of Record published: May 17, 2017 (version 2)


© 2017, Harris & Pritchard

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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  1. Kelley Harris
  2. Jonathan K Pritchard
Rapid evolution of the human mutation spectrum
eLife 6:e24284.

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