A simple method of removing the effect of a bottleneck and unequal population sizes on pairwise genetic distances

In this paper, we derive the expectation of two popular genetic distances u nder a model of pure population fission allowing for unequal population siz es. Under the model, we show that conventional genetic distances are not Pr oportional to the divergence time and generally overestimate it due to uneq ual genetic drift and to a bottleneck effect at the divergence time. This b ias cannot be totally removed even if the present population sizes are know n. Instead, we present a method to estimate the divergence times between po pulations which is based on the average number of nucleotide differences wi thin and between populations. The method simultaneously estimates the diver gence time, the ancestral population size and the relative sizes of the der ived populations. A simulation study revealed that this method is essential ly unbiased and that it leads to better estimates than traditional approach es for a very wide range of parameter values. Simulations also indicated th at moderate population growth after divergence has little effect on the est imates of all three estimated parameters. An application of our method to a comparison of humans and chimpanzee mitochondrial DNA diversity revealed t hat common chimpanzees have a significantly larger female population size t han humans.