Rapid evolution of the human mutation spectrum

Abstract
Data availability
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Abstract

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.

http://www.internationalgenome.org
(2016) Simons Genome Diversity Project
Directions for downloading available here: http://simonsfoundation.s3.amazonaws.com/share/SCDA/datasets/2014_11_12/StepstodownloadtheSGDPdataset_v4.docx.

https://www.simonsfoundation.org/life-sciences/simons-genome-diversity-project-dataset/
(2013) Great Ape Genome Diversity Project
PRJNA189439, SRP018689.

http://biologiaevolutiva.org/greatape/
(2016) Exome Aggregation Consortium
Summary data publicly available for download at http://exac.broadinstitute.org/downloads.

http://exac.broadinstitute.org

Article and author information

Author details

Kelley Harris

Genetics, Stanford University, Stanford, CA, United States

For correspondence
kelleyh@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0302-2523
Jonathan K Pritchard

Department of Genetics, Stanford University, Stanford, United States

For correspondence
pritch@stanford.edu

Competing interests
The authors declare that no competing interests exist.

Funding

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.

Copyright

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.