Controlling Type-I Error of the McDonald-Kreitman Test in Genomewide Scans for Selection on Noncoding DNA

Departures from the assumption of homogenously interdigitated neutral and putatively selected sites in the McDonald-Kreitman test can lead to false rejections of the neutral model in the presence of intermediate levels of recombination. This problem is exacerbated by small sample sizes, nonequilibrium demography, recombination rate variation, and in comparisons involving more recently diverged species. I propose that establishing significance levels by coalescent simulation with recombination can improve the fidelity of the test in genomewide scans for selection on noncoding DNA.