Impact of selection on allele frequency spectrum and gene genealogy in the infinite-site model. Panels A, C, and E are schematic allele frequency spectra (AFSs) of the infinite-site model under selective neutrality, positive selection, and negative selection, respectively. Bar graphs are “observed” spectra, and dashed lines are expectations under selective neutrality. Panels B, D, and F are schematic genealogies of n (= 10) sampled sequences that contain a mutation that is selectively neutral, positively selected, and negatively selected, respectively. Open circles are wild type and selectively neutral mutant sequences (or derived alleles). Shaded circles represent mutant sequences that are positively or negatively selected. A lightening bolt represents a mutation event that gave rise to the mutant sequence(s) in each sample. We can see that it is harder to distinguish a single negatively selected mutation event (E,F) from a neutral one (A,B) than to distinguish a single positively selected mutation event (C,D) from a neutral one, because common features of negatively selected mutations are also quite common among selectively neutral mutations. (See Methods for details).