Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes
Mark Lipson, Po-Ru Loh, Sriram Sankararaman, Nick Patterson, Bonnie Berger, David Reich
The human mutation rate is an essential parameter for studying the evolution of our species, interpreting present-day genetic variation, and understanding the incidence of genetic disease. Nevertheless, our current estimates of the rate are uncertain. Classical methods based on sequence divergence have yielded significantly larger values than more recent approaches based on counting de novo mutations in family pedigrees. Here, we propose a new method that uses the fine-scale human recombination map to calibrate the rate of accumulation of mutations. By comparing local heterozygosity levels in diploid genomes to the genetic distance scale over which these levels change, we are able to estimate a long-term mutation rate averaged over hundreds or thousands of generations. We infer a rate of 1.65 +/- 0.10 x 10^(-8) mutations per base per generation, which falls in between phylogenetic and pedigree-based estimates, and we suggest possible mechanisms to reconcile our estimate with previous studies. Our results support intermediate-age divergences among human populations and between humans and other great apes.
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