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of the genetic architecture of human populations derived from molecular methods bears a strong resemblance to that derived from classical human genetics (Cavalli-Sforza et al., 1994). Africans maintain the most genetic diversity, and the most distant migrants out of Africa retain the least due to successive bottlenecks. Selective sweeps and genetic drift have similar effects on the genome, so the most efficient estimation methods for dating selective sweeps are those which use selectively neutral variation to estimate population sizes and control for the effects of drift. The effects of selection on potentially nonneutral variation are then apparent as departures from expectations based on a neutral model (Rogers, 2001; Williamson et al., 2005). To this point, limitations in the size and nature of the samples of sequenced human DNA do not allow high confidence in either the population or selection reconstructions. The continuing fall in the costs of sequencing will increase sample sizes and coverage, and statistical methods will most likely continue to improve as well.

Sabeti et al. (2006) review the methods for detecting the action of selection on the genome on various timescales. On the longest timescales, selection is evidenced by functionally significant differences between species. For example, the FOXP2 gene has two functionally significant differences between humans and chimpanzees. Preliminary sequences of Neandertal DNA suggest that we share these two changes with that species, thus placing the evolution of these changes before the separation of the two species several hundred thousand years ago (but see a discussion of problems with this interpretation below). Selective changes will show an excess of changes at sites that change amino acids of proteins compared with synonymous sites that do not. At shorter timescales, 250 kya, positive selection leaves a signature of reduced diversity in genes linked to the target of the selective sweep due to hitchhiking. Mutation and drift eventually restore this diversity, but in the meantime an excess of rare alleles in the linked region provides an estimate of the timing of the selective sweep. At timescales 80 kya, the linked region will contain an excess of derived alleles that have hitchhiked to high frequency along with the allele that was the target of selection. As human populations left Africa and became exposed to divergent selection in different environments and cultures, different alleles would have been swept to high frequency in different populations (60 kya). Even if selection pressures are the same in different populations, and an allele with the same function is selected in different populations, the alleles in the different populations are likely to contain neutral differences in sequence. The LCT regulatory gene down-regulates the secretion of lactase postweaning in most human populations. In western Eurasian and African dairying populations the gene is rendered nonfunctional, so that adults continue to secrete lactase and to benefit from lactose. Sequencing of the adult secretion variants of LCT from western

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