Study: Mutation Rate Variability across Human Y-Chromosome Haplogroups

 A small post about a relevant study that was published in 2020.

Qiliang Ding, Ya Hu, Amnon Koren, Andrew G Clark, Mutation Rate Variability across Human Y-Chromosome Haplogroups, Molecular Biology and Evolution, Volume 38, Issue 3, March 2021, Pages 1000–1005, https://doi.org/10.1093/molbev/msaa268

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.

From the supplement 

For the Xue et al. (2009) rate, we identified the following haplogroups having significantly lower relative somatic mutation rate: E1b, R1a, and R1b. For these haplogroups, their actual mutation rate may be lower than the Xue et al. (2009) rate, and thus divergence times may be underestimated.

 

R1b, E1b, and R1a have the shortest branch lengths

 This is YFull's age calculation method:

The second formula uses an assumed mutation rate of 144.41 years (0.8178*10-9, which is the average of the mutation rates of the ancient Anzick-1 sample and of a group of known genealogies, and an assumed age of 60 years for living providers of YFull samples.

Y-Full has the most accurate Y haplogroup tree due to the largest numbers of SNPs utilized, however, they also use a common mutation rate across haplogroups. 

Summary: 

R1b, E1b & R1a Y-chromosomes have lower somatic mutation rates than others due to shorter branch lengths, and therefore expected TMRCA & formation dates of these clades and subclades are most likely underestimated. YFull uses a common mutation rate across Y Haplogroups, therefore its TMRCA and formation dates for R1b, E1b, and R1a (and subclades) are underestimated.