Evidence for population growth in humans is confounded by fine-scale population structure.

Although many studies have reported human polymorphism data, there has been no analysis of the effect of sampling design on the patterns of variability recovered. Here, we consider which factors affect a summary of the allele-frequency spectrum. The most important variable to emerge from our analysis is the number of ethnicities sampled: studies that sequence individuals from more ethnicities recover more rare alleles. These observations are consistent with fine-scale geographic differentiation as well as population growth. They suggest that the geographic sampling strategy should be considered carefully, especially when the aim is to infer the demographic history of humans.