A Hierarchical Bayesian Model for Next-Generation Population Genomics

The demography of populations and natural selection shape genetic variation across the genome and understanding the genomic consequences of these evolutionary processes is a fundamental aim of population genetics. We have developed a hierarchical Bayesian model to quantify genome-wide population structure and identify candidate genetic regions affected by selection. This model improves on existing methods by accounting for stochastic sampling of sequences inherent in next-generation sequencing (with pooled or indexed individual samples) and by incorporating genetic distances among haplotypes in measures of genetic differentiation. Using simulations we demonstrate that this model has a low falsepositive rate for classifying neutral genetic regions as selected genes (i.e., fST outliers), but can detect recent selective sweeps, particularly when genetic regions in multiple populations are affected by selection. Nonetheless, selection affecting just a single population was difficult to detect and resulted in a high falsenegative rate under certain conditions. We applied the Bayesian model to two large sets ofhuman population genetic data. We found evidence of widespread positive and balancing selection among worldwide human populations, including many genetic regions previously thought to be under selection. Additionally, we identified novel candidate genes for selection, several of which have been linked to human diseases. This model will facilitate the population genetic analysis of a wide range of organisms on the basis of nextgeneration sequence data.