Localization of adaptive variants in human genomes using averaged one-dependence estimation.

Statistical methods for identifying adaptive mutations from population genetic data face several obstacles: assessing the significance of genomic outliers, integrating correlated measures of selection into one analytic framework, and distinguishing adaptive variants from hitchhiking neutral variants. Here, we introduce SWIF(r), a probabilistic method that detects selective sweeps by learning the distributions of multiple selection statistics under different evolutionary scenarios and calculating the posterior probability of a sweep at each genomic site. SWIF(r) is trained using simulations from a user-specified demographic model and explicitly models the joint distributions of selection statistics, thereby increasing its power to both identify regions undergoing sweeps and localize adaptive mutations. Using array and exome data from 45 ‡Khomani San hunter-gatherers of southern Africa, we identify an enrichment of adaptive signals in genes associated with metabolism and obesity. SWIF(r) provides a transparent probabilistic framework for localizing beneficial mutations that is extensible to a variety of evolutionary scenarios

Integrating the signatures of demic expansion and archaic introgression in studies of human population genomics

Human population genomic studies have repeatedly observed a decrease in heterozygosity and an increase in linkage disequilibrium with geographic distance from Africa. While multiple demographic models can generate these patterns, many studies invoke the serial founder effect model, in which populations expand from a single origin and each new population\u27s founders represent a subset of genetic variation in the previous population. The model assumes no admixture with archaic hominins, however, recent studies have identified loci in Homo sapiens bearing signatures of archaic introgression. These results appear to contradict the validity of analyses invoking the serial founder effect model, but we show these two perspectives are compatible. We also propose using the serial founder effect model as a null model for determining the signature of archaic admixture in modern human genomes at different geographic and genomic scales

Localization of adaptive variants in human genomes using averaged one-dependence estimation

Selective sweeps are events in which beneficial mutations spread rapidly through a population. Here, Sugden et al. develop SWIF(r), a probabilistic classification framework for detecting and localizing selective sweeps, and apply it to genomic data from the ‡Khomani San