Unveiling recent and ongoing adaptive selection in human populations

Abstract

Genome-wide scans for signals of selection have become a routine part of the analysis of population genomic variation datasets and have resulted in compelling evidence of selection during recent human evolution. This Essay spotlights methodological innovations that have enabled the detection of selection over very recent timescales, even in contemporary human populations. By harnessing large-scale genomic and phenotypic datasets, these new methods use different strategies to uncover connections between genotype, phenotype, and fitness. This Essay outlines the rationale and key findings of each strategy, discusses challenges in interpretation, and describes opportunities to improve detection and understanding of ongoing selection in human populations.

Fig 1. Overall framework of selection bridging population genetics and quantitative genetics models.

In this conceptual framework, selection on genotype is mediated by fitness-relevant phenotype and manifests in allele frequency changes and genetic variation patterns. In any specific environment, genotype and environment together shape the phenotype of an individual, which in turn determines the fitness. In addition to its direct effect on the phenotype (solid purple arrow), the environment also modifies the genotype-to-phenotype mapping (i.e., genotype-by-environment interaction; indicated by the dotted purple arrow) and phenotype-to-fitness mapping (dashed purple arrow). Through interactions with other evolutionary forces (indicated by the brown plus sign), natural selection shapes the allele frequency trajectory over time and leaves footprints in genomic variation in present-day populations.

Fig 2. Signals of recent positive selection in genetic variation and corresponding methods for selection inference.

(A) The hallmark of positive selection is faster allele frequency increase than would be expected under neutrality. (B) The rapid allele frequency change leaves footprints in the surrounding genomic region, although the specific patterns depend on the strength, tempo, and mode of selection (e.g., selection on standing variation versus on de novo variants). (C) Major methods for detecting positive selection based on present-day genetic variation.

Fig 3. Common strategies for detecting signatures of recent or ongoing selection.

(A) A “genotype-focused” strategy focuses on the cumulative effects of historical selection on genetic variation patterns and relies on population genetics modeling to tease apart the influence of other evolutionary forces. Ancient DNA data provide direct information on allele frequency changes, which helps reduce inference uncertainty and confounding by demographic history. (B) A “fitness-focused” strategy focuses on direct association between genotype and fitness component(s) and utilizes allele frequency changes within one generation to detect selection in contemporary populations. As a special case of this strategy, between-sex differences in adult allele frequency or effect size of association to fitness components can be leveraged to detect sex-differential selection. (C) A “phenotype-focused” strategy relies on aggregation of selection signals revealed by genotype-focused or fitness-focused strategies across trait-associated variants identified by genome-wide association studies (GWAS).