Estimating time to the most recent common ancestor (TMRCA): comparison and application of eight methods.

Investigating how an ancestral population diverges to give rise to distinct subpopulations remains a fundamental pursuit in population genetics. There is broad consensus for the 'Out-of-Africa' hypothesis that states that modern humans arose ∼200 000 years ago in Africa and spread throughout the continent ∼100 000 years ago. This was followed by several waves of major population dispersals across the globe, although the exact nature of the population divergence remains debatable. Existing methods to estimate population divergence time differ in their methodological frameworks and demographic assumptions, and require different types of genetic data as input. These fundamental differences often result in the methods producing inconsistent estimates of the population divergence time, further confounding attempts to robustly uncover the history of human migration, especially when most population genetic studies do not employ multiple methods to estimate the time to the most recent common ancestor (TMRCA). Here, we chose eight popular methods for estimating TMRCA and evaluated their robustness and accuracy in correctly identifying the true TMRCA through a series of simulations that mimicked different evolutionary scenarios. We subsequently applied all eight methods to estimate the population divergence time between Southeast Asian Malays and South Asian Indians using deep whole-genome sequencing data.