Identifying and classifying shared selective sweeps from multilocus data

Positive selection causes beneficial alleles to rise to high frequency, resulting in a selective sweep of the diversity surrounding the selected sites. Accordingly, the signature of a selective sweep in an ancestral population may still remain in its descendants. Identifying genomic regions under selection in the ancestor is important to contextualize the timing of a sweep, but few methods exist for this purpose. To uncover genomic regions under shared positive selection across populations, we apply the theory of the expected haplotype homozygosity statistic H12, which detects recent hard and soft sweeps from the presence of high-frequency haplotypes. Our statistic, SS-H12, is distinct from other statistics that detect shared sweeps because it requires a minimum of only two populations, and properly identifies independent convergent sweeps and true ancestral sweeps, with high power. Furthermore, we can apply SS-H12 in conjunction with the ratio of a different set of expected haplotype homozygosity statistics to further classify identified shared sweeps as hard or soft. Finally, we identified both previously-reported and novel shared sweep candidates from whole-genome sequences of global human populations. Previously-reported candidates include the well-characterized ancestral sweeps at LCT and SLC24A5 in Indo-European populations, as well as GPHN worldwide. Novel candidates include an ancestral sweep at RGS18 in sub-Saharan African populations involved in regulating the platelet response and implicated in sudden cardiac death, and a convergent sweep at C2CD5 between European and East Asian populations that may explain their different insulin responses.