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

Natural Selection Affects Multiple Aspects of Genetic Variation at Putatively Neutral Sites across the Human Genome

A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations

Determinants of genetic diversity

International audienceGenetic polymorphism varies among species and within genomes, and has important implications for the evolution and conservation of species. The determinants of this variation have been poorly understood, but population genomic data from a wide range of organisms now make it possible to delineate the underlying evolutionary processes, notably how variation in the effective population size (Ne) governs genetic diversity. Comparative population genomics is on its way to providing a solution to 'Lewontin's paradox' — the discrepancy between the many orders of magnitude of variation in population size and the much narrower distribution of diversity levels. It seems that linked selection plays an important part both in the overall genetic diversity of a species and in the variation in diversity within the genome. Genetic diversity also seems to be predictable from the life history of a species