1000 Genomes Pilot Data Suggests Recent Selective Sweeps Rare in Human Lineage

Via GenomeWeb Daily News:

"Our findings suggest that recent human adaptation has not taken place through the arrival and spread of single changes of large effect, but through shifts of frequency in many places of the genome," co-senior author Mary Przeworski, a human genetics, ecology, and evolution researcher at the University of Chicago, said in a statement. "It suggests that human adaptation, like most common human diseases, has a complex genetic architecture."

Przeworski et al. Classic Selective Sweeps Were Rare in Recent Human Evolution. Science 18 February 2011: vol. 331 no. 6019 pp. 920-924. DOI: 10.1126/science.1198878

Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of “classic selective sweeps” (in which a beneficial mutation arises and rapidly fixes in the population).Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.

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This conclusion does not imply that humans have experienced few phenotypic adaptations, or that adaptations have not shaped genomic patterns of diversity. Comparisons of diversity and divergence levels at putatively functional versus neutral sites, for example, suggest that 10 to 15% [and possibly as many as 40% (29)] of amino acid differences between humans and chimpanzees were adaptive [e.g., (30)], as were 5% of substitutions in conserved noncoding regions (22, 29) and ~20% in UTRs (22). Given the paucity of classic sweeps revealed by our findings, an excess of functional divergence would point to the importance of other modes of adaptation. One way to categorize modes of adaptation is in terms of their effect on the allele frequencies at sites that affect the beneficial phenotype. In this view, classic sweeps bring new alleles to fixation; selection on standing variation or on multiple beneficial alleles brings rare or intermediate frequency alleles to fixation; and other forms of adaptation, such as selection on polygenic traits, increase or decrease allele frequencies to a lesser extent. Such changes in allele frequencies can decrease variation at closely linked sites—to a lesser extent than in a full sweep—and might therefore contribute to a reduction in diversity near functional elements (31) as well as to excess divergence. Alternatives to classic sweeps are likely for parameters applicable to human populations (7, 32); in particular, many phenotypes of interest are quantitative and plausibly result from selection at many loci of small effect (8).

An important implication is that in the search for targets of human adaptation, a change in focus is warranted. To date, selection scans have relied almost entirely on the sweep model, either explicitly (by considering strict neutrality as the null hypothesis and a classic sweep as the alternative) or implicitly (by ranking regions by a statistic thought to be sensitive to classic sweeps and focusing on the tails of the empirical distribution). It appears that few adaptations in humans took the form that these approaches are designed to detect, such that low-hanging fruits accessible by existing approaches may be largely depleted. Conversely, the more common modes of adaptation likely remain undetected. Thus, to dissect the genetic basis of human adaptations and assess what fraction of the genome was affected by positive selection, we need new tests to detect other modes of selection, such as comparisons between closely related populations that have adapted to drastically different environments [e.g., (33)] or methods that consider loci that contribute to the same phenotype jointly [e.g., (34)]. Moreover, if alleles that contribute to recent adaptations are often polymorphic within a population, genome-wide association studies should be highly informative.