A common assumption in dating patrilineal events using Y-chromosome sequencing data is that the Y-chromosome mutation rate is invariant across haplogroups. Previous studies revealed interhaplogroup heterogeneity in phylogenetic branch length. Whether this heterogeneity is caused by interhaplogroup mutation rate variation or nongenetic confounders remains unknown. Here, we analyzed whole-genome sequences from cultured cells derived from >1,700 males. We confirmed the presence of branch length heterogeneity. We demonstrate that sex-chromosome mutations that appear within cell lines, which likely occurred somatically or in vitro (and are thus not influenced by nongenetic confounders) are informative for germline mutational processes. Using within-cell-line mutations, we computed a relative Y-chromosome somatic mutation rate, and uncovered substantial variation (up to 83.3%) in this proxy for germline mutation rate among haplogroups. This rate positively correlates with phylogenetic branch length, indicating that interhaplogroup mutation rate variation is a likely cause of branch length heterogeneity.
Keywords: DNA replication timing; Y chromosome; haplogroup; mutation rate.
© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.