Two variants that were highly differentiated between the Kalash and the neighboring Pakistani populations stood out. One variant, rs4988235 (c.−13910C>T), which influences lactase (LCT [MIM: 603202]) expression and confers lactose tolerance, is fixed for the ancestral lactose-intolerant allele in the Kalash. The derived allele, however, is reported to be present at a moderate frequency (average 29%) in Pakistan.32 Forward-time simulations demonstrated that the observed pattern cannot easily be explained by recent genetic drift, given that only 0.1% of the 1,000 simulations achieved fixation for the ancestral allele after 500 generations (Figure 4A).