PT  - JOURNAL ARTICLE
AU  - Mark Lipson
AU  - Po-Ru Loh
AU  - Sriram Sankararaman
AU  - Nick Patterson
AU  - Bonnie Berger
AU  - David Reich
TI  - Calibrating the Human Mutation Rate via Ancestral Recombination Density in Diploid Genomes
AID  - 10.1101/015560
DP  - 2015 Jan 01
TA  - bioRxiv
PG  - 015560
4099  - http://biorxiv.org/content/early/2015/11/13/015560.short
4100  - http://biorxiv.org/content/early/2015/11/13/015560.full
AB  - 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. Most notably, recent approaches based on counting de novo mutations in family pedigrees have yielded significantly smaller values than classical methods based on sequence divergence. 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 1.61 ± 0.13 × 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.