Estimating divergence time with the use of microsatellite genetic distances: Impacts of population growth and gene flow

Genetic distances play an important role in estimating divergence time of bifurcated populations. However, they can be greatly affected by demographic processes, such as migration and population dynamics, which complicate their interpretation. For example, the widely used distance for microsatellite loci, (delta mu)(2), assumes constant population size, no gene flow, and mutation-drift equilibrium. It is shown here that (delta mu)(2) strongly underestimates divergence time if populations are growing and/or connected by gene flow. In recent publications, the average estimate of divergence time between African and non-African populations obtained by using (delta mu)(2) is about 34,000 years, although archaeological data show a much earlier presence of modern humans out of Africa. I introduce a different estimator of population separation time based on microsatellite statistics, T-D, that does not assume mutation-drift equilibrium, is independent of population dynamics in the absence of gene flow, and is robust to weak migration flow for growing populations. However, it requires a knowledge of the variance in the number of repeats at the beginning of population separation, V-0. One way to overcome this problem is to find minimal and maximal bounds for the variance and thus obtain the earliest and latest bounds for divergence time (this is not a confidence interval, and it simply reflects an uncertainty about the value of V-0 in an ancestral population). Another way to avoid the uncertainty is to choose from among present populations a reference whose variation is presumably close to what it might have been in an ancestral population. A different approach for using T-D is to estimate the time difference between adjacent nodes on a phylogenetic population tree. Using data on variation at autosomal short tandem repeat loci with di-, tri-, and tetranucleotide repeats in worldwide populations, T-D gives an estimate of 57,000 years for the separation of the out-of-Africa branch of modern humans from Africans based on the value of V-0 in the Southern American Indian populations; the earliest bound for this event has been estimated to be about 135,000 years. The data also suggest that the Asian and European populations diverged from each other about 20,000 years, after the occurrence of the out-of-Africa branch.