Localizing recent adaptive evolution in the human genome

Abstract

Identifying genomic locations that have experienced selective sweeps is an important first step toward understanding the molecular basis of adaptive evolution. Using statistical methods that account for the confounding effects of population demography, recombination rate variation, and single-nucleotide polymorphism ascertainment, while also providing fine-scale estimates of the position of the selected site, we analyzed a genomic dataset of 1.2 million human single-nucleotide polymorphisms genotyped in African-American, European-American, and Chinese samples. We identify 101 regions of the human genome with very strong evidence (p < 10(-5)) of a recent selective sweep and where our estimate of the position of the selective sweep falls within 100 kb of a known gene. Within these regions, genes of biological interest include genes in pigmentation pathways, components of the dystrophin protein complex, clusters of olfactory receptors, genes involved in nervous system development and function, immune system genes, and heat shock genes. We also observe consistent evidence of selective sweeps in centromeric regions. In general, we find that recent adaptation is strikingly pervasive in the human genome, with as much as 10% of the genome affected by linkage to a selective sweep.

Figure 1. Evidence for Selective Sweeps in Centromeric Regions of Several Chromosomes, as Measured by the p Value of the CLR Test in Three Human Populations

Vertical dashed lines indicate the positions of the centromere, and p values are plotted on a log scale.

Figure 2. Sliding Window Analysis of the KITLG Region of Chromosome 12, Along with Gene Models of All refseq Genes in the Region

The horizontal dashed line represents the p < 0.001 critical value of the population-specific CLR tests generated using a conservative estimate of the average recombination rate in the region.

Figure 3. A Comparison of p Values of the CLR Test, Calculated from Simulations of Models Assuming a Constant Recombination Rate and Models That Include Recombination Hotspots

(A) The combined sample. (B) The African-American sample. (C) The European-American sample. (D) The Chinese sample. p Values are highly consistent between constant recombination and hotspot models, indicating that the CLR test is robust to recombination rate variation. Note that both axes are on a log scale.

Figure 4. The Null Distribution of the CLR Statistic in a Non-African Population for Non-African Bottleneck Models of Varying Strength, As Well As the Complex Schaffner Model

Figure 5. The Distribution of p Values for the CLR Test of a Selective Sweep

Figure 6. The Fraction of Tests for Which the Null Hypothesis Is False, Estimated Using a FDR Procedure and Shown for Four Alternative Evolutionary Models

(1) The equilibrium, random mating, neutral model. (2) The Marth et al. [25] bottleneck and growth model. (3) The most conservative non-African bottleneck model. (4) The complex demographic and recombination model calibrated by Schaffner et al. [50].