The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation

Abstract

There has long been interest in understanding the genetic basis of human adaptation. To what extent are phenotypic differences among human populations driven by natural selection? With the recent arrival of large genome-wide data sets on human variation, there is now unprecedented opportunity for progress on this type of question. Several lines of evidence argue for an important role of positive selection in shaping human variation and differences among populations. These include studies of comparative morphology and physiology, as well as population genetic studies of candidate loci and genome-wide data. However, the data also suggest that it is unusual for strong selection to drive new mutations rapidly to fixation in particular populations (the 'hard sweep' model). We argue, instead, for alternatives to the hard sweep model: in particular, polygenic adaptation could allow rapid adaptation while not producing classical signatures of selective sweeps. We close by discussing some of the likely opportunities for progress in the field.

Figure 1. Conflicting evidence of population-specific selection

(A) The x-axis shows the signed difference in derived allele frequency between HapMap Yoruba and east Asians. The y-axis shows the fractions of SNPs in each bin of frequency differences that are genic, and nongenic, respectively, divided by the total fraction of SNPs that are genic, and nongenic, respectively. (B) The x-axis shows the mean pairwise FST between all pairs of HGDP populations with sample sizes >15 individuals (the values of four arbitrary pairs comparing France, Palestine, Han and Yoruba are indicated to provide a sense of scale). The y-axis shows the value of the most extreme allele frequency difference for each population at any of the 640,000 genotyped SNPs. (C) The three curves show the distributions of XP-EHH, a measure of haplotype diversity [34] for (i) random SNPs in east Asians, (ii) SNPs with a frequency difference >90% between HapMap Yoruba and east Asians, and (iii) simulated SNPs with a selective advantage of 1% and a frequency difference >90%, assuming a uniform rate of input of favored mutations. In fact, the middle curve is most similar to data simulated under a neutral model, but conditioned on the frequency difference of >90% (not shown). All three plots are redrawn from [22].

Figure 2. The probability of sweeps from standing variation following an environmental change

(A) Probability that a full sweep occurs from standing variation, as a function of the mutational target size and the strength of selection after the environmental switch. (B) Probability that a sweep occurs from standing variation, conditional on a sweep occurring either from standing variation or from new variation that arises within the first 1000 generations after the environmental change. The model is as described in the text and in [41]. Parameters: Prior to the environmental switch, variation is deleterious with 2N_es = −10. We assume N_e = 10,000 and µ = 2 × 10⁻⁸. All selection is assumed additive. Modified with permission from [41].

Figure 3. A cartoon illustration of the hard sweep and polygenic adaptation models

The horizontal blue lines represent haplotypes, and the red lines indicate regions that are identical by descent (IBD). The red circles indicate alleles that are favored following an environmental change. In the monogenic (hard selection) model, selection drives a new mutation to fixation, creating a large region of IBD. In the polygenic model, prior to selection red alleles exist at modest frequencies at various loci across the genome. (The red alleles can be thought of as being alleles that all shift a particular phenotype in the same direction, e.g., alleles that increase height.) After selection, the genome-wide abundance of favored alleles has increased, but in this cartoon they have not fixed at any locus. In this example, at some loci selection has acted on new variants, creating signals of partial sweeps at those loci (the x-axis scale is not necessarily the same in the left- and right-hand plots).