Human Population Differentiation Is Strongly Correlated with Local Recombination Rate

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 FST shows 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 and FST 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: 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.