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Targeted resequencing of two genes, RAGE and POLL, confirms findings from a genome-wide scan for adaptive evolution and provides evidence for positive selection in additional populations.

The availability of multiple genome-wide human polymorphism datasets has led to an increase in efforts to scan the genome for signals of positive selection. As a result, the number of loci in the human genome predicted to be adaptively evolving increases monthly. Yet, these numerous genome-wide scans have identified minimally overlapping sets of candidate loci, potentially due to biases in genotype versus sequence data or power of statistical tests to detect selection in different time frames. Because of these issues, a critical step is to confirm the evidence for positive selection through direct sequencing. In this study, we describe the resequencing and analysis of two loci, RAGE and POLL, that were identified by a recent genome-wide scan of the Perlegen data to be under selection in the Han Chinese population. By resequencing these loci in additional populations, we have found that the evolutionary history of these regions is more complex than observed in the initial genome-wide scan and that the sweep patterns are shared across several populations. The resequencing data provide evidence for selection on RAGE in the non-African populations and on POLL in the Asian and Sub-Saharan African populations. In addition to confirming the signatures of selection from the genome-wide scan, direct resequencing reveals more extensive patterns of selection than the genotype data.