Counterbalancing the time-dependence effect on the Human Mitochondrial DNA Molecular Clock

Background The molecular clock is the most important genetic tool to estimate evolutionary timescales. However, the detection of a time dependency effect on the mutation rate estimates is complicating its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study I propose a new algorithm to estimate the coalescent age of phylogenetically related sequences, taking into account the observed time dependency effect on the molecular rate detected by others.Results Applying this method to real human mitochondrial DNA trees, with shallow and deep topologies, I have obtained significantly older molecular ages for the main events of human evolution than in previous estimates. These ages are in close agreement with the most recent archaeological and paleontological records that are in favor of an emergence of early anatomically modern humans in Africa at 315 ± 34 thousand years ago and the presence of recent modern humans out of Africa as early as 174 ± 48 thousand years ago. Furthermore, in the implementation process, we demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size which is more in accordance with the fact that, under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift.Conclusions I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time dependence effect observed for the substitution rate.