Human molecular evolutionary rate, time dependency and transient polymorphism effects viewed through ancient and modern mitochondrial DNA genomes

Vicente M Cabrera

doi:10.1038/s41598-021-84583-1

Abstract

Human evolutionary genetics gives a chronological framework to interpret the human history. It is based on the molecular clock hypothesis that suppose a straightforward relationship between the mutation rate and the substitution rate with independence of other factors as demography dynamics. Analyzing ancient and modern human complete mitochondrial genomes we show here that, along the time, the substitution rate can be significantly slower or faster than the average germline mutation rate confirming a time dependence effect mainly attributable to changes in the effective population size of the human populations, with an exponential growth in recent times. We also detect that transient polymorphisms play a slowdown role in the evolutionary rate deduced from haplogroup intraspecific trees. Finally, we propose the use of the most divergent lineages within haplogroups as a practical approach to correct these molecular clock mismatches.

Highlights

Evolutionary genetics studies human history within a chronological molecular context
The significant differences observed between mutation rate and evolutionary rate estimations have not disappeared when uniparental markers have been substituted by massive whole genome s equencing11–13 or when the mutation rate has been substituted by the recombination r ate14
We have suggested that accepting a dependency of the divergence rate on past demographic dynamics, and trusting on the average germline mutation rate as a reliable value, it is possible to reconcile the archaeological dates with the genetic o nes20

Summary

Introduction

Evolutionary genetics studies human history within a chronological molecular context. At this respect, its main tool is the molecular clock which established that the rate of divergence between proteins or DNA sequences, measured as mutational differences between lineages, is proportional to the time elapsed since their initial separation. Each time more sophisticated models have to be implemented to take into account this heterogeneity. Each time more sophisticated models have to be implemented to take into account this heterogeneity2 Another problem detected with this molecular timescale is that it varies, intra and interspecifically, along the history of the lineage e xamined. At least in humans, these improvements have not varied substantially the evolutionary rates previously obtained with modern s equences. We have suggested that accepting a dependency of the divergence rate on past demographic dynamics, and trusting on the average germline mutation rate as a reliable value, it is possible to reconcile the archaeological dates with the genetic o nes

Methods

Results

Conclusion