Colloquium paper: human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency

Abstract

Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of ecoregions and dietary components. These aspects of human environments have changed dramatically during human evolution, giving rise to new selective pressures. To understand the genetic basis of human adaptations, we combine population genetics data with ecological information to detect variants that increased in frequency in response to new selective pressures. Our approach detects SNPs that show concordant differences in allele frequencies across populations with respect to specific aspects of the environment. Genic and especially nonsynonymous SNPs are overrepresented among those most strongly correlated with environmental variables. This provides genome-wide evidence for selection due to changes in ecoregion, diet, and subsistence. We find particularly strong signals associated with polar ecoregions, with foraging, and with a diet rich in roots and tubers. Interestingly, several of the strongest signals overlap with those implicated in energy metabolism phenotypes from genome-wide association studies, including SNPs influencing glucose levels and susceptibility to type 2 diabetes. Furthermore, several pathways, including those of starch and sucrose metabolism, are enriched for strong signals of adaptations to a diet rich in roots and tubers, whereas signals associated with polar ecoregions are overrepresented in genes associated with energy metabolism pathways.

Fig. 1.

Transformed allele frequency plotted against population for the variables that showed the strongest enrichment of signal for genic and NS SNPs. Patterns of variation in allele frequencies are shown for (A) the main dietary component roots and tubers, (B) the subsistence strategy foraging, and for (C) polar and (D) dry ecoregions. SNPs were polarized according to the relative difference between the two categories in the first region where both were present; then, transformed allele frequencies were computed by subtracting the mean allele frequency across populations. SNPs with rank <10⁻⁴ are included in the plots. Vertical lines separate populations into one of seven major geographic regions (from left to right: sub-Saharan Africa, Europe, Middle East, West Asia, East Asia, Oceania, and the Americas). Red denotes populations that are members of the dichotomous category, and all other populations are blue. Lines are drawn through the mean for the set of populations in a given region that are part of the category of interest, and gray shading denotes the central 50% interval.

Fig. 2.

Average frequencies for PRLP2 W358X (rs4751995) across populations in each major geographic region.