Human adaptation over the past 40,000 years

Abstract

Over the past few years several methodological and data-driven advances have greatly improved our ability to robustly detect genomic signatures of selection in humans. New methods applied to large samples of present-day genomes provide increased power, while ancient DNA allows precise estimation of timing and tempo. However, despite these advances, we are still limited in our ability to translate these signatures into understanding about which traits were actually under selection, and why. Combining information from different populations and timescales may allow interpretation of selective sweeps. Other modes of selection have proved more difficult to detect. In particular, despite strong evidence of the polygenicity of most human traits, evidence for polygenic selection is weak, and its importance in recent human evolution remains unclear. Balancing selection and archaic introgression seem important for the maintenance of potentially adaptive immune diversity, but perhaps less so for other traits.

Figure 1:. Genomic signatures of adaptation.

Selection on variants affecting a beneficial trait. In a hard sweep, a new (or rare) mutation (red) on a single haplotype increases rapidly in frequency. Variants on the same haplotype (grey) also increase (“hitchhike”), reducing diversity around the selected site (97). Over time, recombination, drift and mutation break down the sweep signature. In a soft sweep (98), the selected variant may already be present on multiple haplotypes (red), or there may be new selected mutations (green) as the sweep is in progress. Diversity is reduced around the sweep but not by as much as a hard sweep. In practice, this signature may be difficult to distinguish from an incomplete hard sweep. In polygenic adaptation (42), variants at many loci genome-wide change frequency; trait-increasing alleles (red) increase in frequency while trait-decreasing alleles (blue) decrease. This process is essentially a large number of weak soft sweeps, but the effects are too small to be detected at any one locus. Variants drift after selection, but mean shifts in frequency are maintained.

Figure 2:. Ancient DNA adds another dimension to selection scans.

A: genome-wide selection scan signals from three different approaches (8, 12, 26) with power to detect selection over different timescales. Y-axis shows log₁₀ quantiles for the top 0.1% of tested markers. B: stratified by geographic location, ancient DNA from 668 individuals reveals distinct trajectories of the lactase persistence allele in different parts of Europe. C: stratified by ancestry derived from the three main source populations of present-day Europe, ancient DNA reconstructs the evolution of the FADS locus (redrawn from (17)).

Figure 3:. Limits to polygenic adaption. A:

If the phenotypic optimum changes over time, polygenic adaptation will not leave a consistent signal of frequency shift. B: Similarly, if effect sizes or direction changes over time due to allelic heterogeneity, or interactions, then polygenic adaption will occur, but will not leave a consistent pattern of frequency shifts. This cartoon shows a population of five haplotypes with three trait-associated SNPs over three time periods, with selection for an increased phenotype. If SNP effects are constant, then trait-increasing SNPs consistently increase in frequency and trait-decreasing SNPs decrease in frequency. On the other hand, if effects change over time, then this signal would be obscured over the long term, even though polygenic adaptation is still occurring. C: Finally, polygenic adaptation may be fundamentally limited by pleiotropy, which constrains the range of possible phenotypes that can be reached (between the dashed lines), or the set of variants that can respond to selection.