Abstract
Few genetic differences between human populations conform to the classic model of positive selection, in which a newly arisen mutation rapidly approaches fixation in one lineage, suggesting that adaptation more commonly occurs via moderate changes in standing variation at many loci. Detecting and characterizing this type of complex selection requires integrating individually ambiguous signatures across genomically and geographically extensive data. Here, we develop a novel approach to test the hypothesis that selection has favored modest divergence at particular loci multiple times in independent human populations. We find an excess of SNPs showing non-neutral parallel divergence, enriched for genic and nonsynonymous polymorphisms in genes encompassing diverse and often disease related functions. Repeated parallel evolution in the same direction suggests common selective pressures in disparate habitats. We test our method with extensive coalescent simulations and show that it is robust to a wide range of demographic events. Our results demonstrate phylogenetically orthogonal patterns of local adaptation caused by subtle shifts at many widespread polymorphisms that likely underlie substantial phenotypic diversity.
Highlights
The predominant population genetics model of adaptation assumes novel advantageous alleles sweep to fixation [1,2], most putative examples of adaptive divergence between human populations lack the full signature of a classic hard sweep [2,3,4,5,6,7,8,9,10]
Adaptive events on timescales corresponding to the human diaspora may often manifest as relatively small changes in allele frequencies at numerous loci that are difficult to distinguish from stochastic changes due to genetic drift, rather than the more dramatic selective sweeps described by classic models of natural selection
In order to test whether a substantial proportion of interpopulation genetic differences are adaptive, we identify loci that have undergone moderate allele frequency changes in multiple independent human lineages, and we test whether these parallel divergence events are more frequent than expected by chance
Summary
The predominant population genetics model of adaptation assumes novel advantageous alleles sweep to fixation [1,2], most putative examples of adaptive divergence between human populations lack the full signature of a classic hard sweep [2,3,4,5,6,7,8,9,10]. Classic sweeps may have played a negligible role in the evolutionary changes that have occurred since the most recent common human ancestor [10], prompting the question of whether the moderately large allele frequency differences observed among modern human populations at a small proportion of loci are adaptive. These divergent loci may indicate more complex and subtle modes of selection, but it is often difficult to demonstrate with statistical confidence that they are not merely the tail end of a stochastic neutral distribution. Studying this evolutionary process can generate a list of candidate sites that likely have functional phenotypic consequences and provide insight into which environments present similar selective pressures
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