1 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America, 3 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, United States of America
Abstract
Allele frequency differences across populations can provide valuable information both for studying population structure and for identifying loci that have been targets of natural selection. Here, we examine the relationship between recombination rate and population differentiation in humans by analyzing two uniformly-ascertained, whole-genome data sets. We find that population differentiation as assessed by inter-continental FSTshows negative correlation with recombination rate, with FST reduced by 10% in the tenth of the genome with the highest recombination rate compared with the tenth of the genome with the lowest recombination rate (P≪10−12). This pattern cannot be explained by the mutagenic properties of recombination and instead must reflect the impact of selection in the last 100,000 years since human continental populations split. The correlation between recombination rate andFST has a qualitatively different relationship for FST between African and non-African populations and for FST between European and East Asian populations, suggesting varying levels or types of selection in different epochs of human history.
Author Summary Top
A common assumption when analyzing patterns of human genetic variation is that most of the genome can be treated as “nearly neutral,” in the sense that the effects of natural selection on allele frequencies are very small compared with the influence of population demographic history. To test the validity of this assumption, we analyzed data from more than a million human polymorphisms and summarized allele frequency differences across populations. We find that, compared with the genome-wide average, allele frequency differences are 7% reduced on average in the tenth of the genome with the highest recombination rate and are 3% increased in the tenth with the lowest rate. Such a correlation cannot be explained by demography. Instead, the pattern reflects the fact that forces of natural selection have had a profound impact on patterns of variation throughout the genome in the last 100,000 years.
Citation: Keinan A, Reich D (2010) Human Population Differentiation Is Strongly Correlated with Local Recombination Rate. PLoS Genet 6(3): e1000886. doi:10.1371/journal.pgen.1000886
Editor: David J. Begun, University of California Davis, United States of America
Received: July 14, 2009; Accepted: February 24, 2010; Published: March 26, 2010
Copyright: © 2010 Keinan, Reich. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: AK and DR were supported by NIH grant U01 HG004168. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: ak735@cornell.edu
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HT/TC: John Hawks
