Appropriate Assignment of Fossil Calibration Information Minimizes the Difference between Phylogenetic and Pedigree Mutation Rates in Humans.

Renata Capellão,Carlos Schrago,Elisa Costa-Paiva

doi:10.3390/life8040049

Renata Capellão, Carlos Schrago + Show 1 more

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https://doi.org/10.3390/life8040049

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Abstract

Studies that measured mutation rates in human populations using pedigrees have reported values that differ significantly from rates estimated from the phylogenetic comparison of humans and chimpanzees. Consequently, exchanges between mutation rate values across different timescales lead to conflicting divergence time estimates. It has been argued that this variation of mutation rate estimates across hominoid evolution is in part caused by incorrect assignment of calibration information to the mean coalescent time among loci, instead of the true genetic isolation (speciation) time between humans and chimpanzees. In this study, we investigated the feasibility of estimating the human pedigree mutation rate using phylogenetic data from the genomes of great apes. We found that, when calibration information was correctly assigned to the human–chimpanzee speciation time (and not to the coalescent time), estimates of phylogenetic mutation rates were statistically equivalent to the estimates previously reported using studies of human pedigrees. We conclude that, within the range of biologically realistic ancestral generation times, part of the difference between whole-genome phylogenetic and pedigree mutation rates is due to inappropriate assignment of fossil calibration information to the mean coalescent time instead of the speciation time. Although our results focus on the human–chimpanzee divergence, our findings are general, and relevant to the inference of the timescale of the tree of life.

Highlights

IntroductionWith the advent of the molecular clock theory in the 1960s, mutation rates have been measured per year [5]
The study of mutation rates constitutes a fundamental problem in genetics and evolution [1,2].Traditionally, the rate at which mutations occur has been measured on a generational basis [3,4].with the advent of the molecular clock theory in the 1960s, mutation rates have been measured per year [5]
Our study focused on the divergence between humans and chimpanzees, overestimation of the phylogenetic rate by incorrect assignment of the calibration information to the coalescent time instead of the speciation time affects any divergence in the tree of life

Summary

Introduction

With the advent of the molecular clock theory in the 1960s, mutation rates have been measured per year [5]. In this sense, the age of the Homo–Pan split, gathered from the fossil record, has been widely used as calibration information for the estimation of the yearly substitution rates in several human loci [6], but only with the sequencing of the genomes of humans and chimpanzees, calculation of whole-genome substitution rates became feasible. Assuming that the age of the Homo–Pan split is approximately 7 million years ago (Ma) [6,10], a yearly substitution rate of 0.09 × 10−8 substitutions/nucleotide site/year (s/s/y) was inferred

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