The genealogy of a sequence subject to purifying selection at multiple sites.

We investigate the effect of purifying selection at multiple sites on both the shape of the genealogy and the distribution of mutations on the tree. We find that the primary effect of purifying selection on a genealogy is to shift the distribution of mutations on the tree, whereas the shape of the tree remains largely unchanged. This result is relevant to the large number of coalescent estimation procedures, which generally assume neutrality for segregating polymorphisms--applying these estimators to evolutionarily constrained sequences could lead to a significant degree of bias. We also estimate the statistical power of several neutrality tests in detecting weak to moderate purifying selection and find that the power is quite good for some parameter combinations. This result contrasts with previous studies, which predicted low statistical power because of the minor effect that weak purifying selection has on the shape of a genealogy. Finally, we investigate the effect of Hill-Robertson interference among linked deleterious mutations on patterns of molecular variation. We find that dependence among selected loci can substantially reduce the efficacy of even fairly strong purifying selection.