The Y-chromosome point mutation rate in humans

Abstract

Mutations are the fundamental source of biological variation, and their rate is a crucial parameter for evolutionary and medical studies. Here we used whole-genome sequence data from 753 Icelandic males, grouped into 274 patrilines, to estimate the point mutation rate for 21.3 Mb of male-specific Y chromosome (MSY) sequence, on the basis of 1,365 meioses (47,123 years). The combined mutation rate for 15.2 Mb of X-degenerate (XDG), X-transposed (XTR) and ampliconic excluding palindromes (rAMP) sequence was 8.71 × 10(-10) mutations per position per year (PPPY). We observed a lower rate (P = 0.04) of 7.37 × 10(-10) PPPY for 6.1 Mb of sequence from palindromes (PAL), which was not statistically different from the rate of 7.2 × 10(-10) PPPY for paternally transmitted autosomes. We postulate that the difference between PAL and the other MSY regions may provide an indication of the rate at which nascent autosomal and PAL de novo mutations are repaired as a result of gene conversion.

Punctuated bursts in human male demography inferred from 1,244 worldwide Y-chromosome sequences

“…Present-day geographical distributions provide strong support for the correspondences we proposed for the initial peopling of most of Eurasia by fully modern humans ~50–55 kya and for the first colonization of the Americas ~15 kya. For later male-specific expansions, we should consider the consequences of alternative mutation rate estimates, as pedigree-based methods relying on variation from the most recent several centuries 8,10,28 may be more relevant. The pedigree-based estimate from the largest set of mutations 8 would lead to a decrease in expansion times by ~15%, increasing the precision of the correspondences proposed for E1b and R1a.…”

“…For later male-specific expansions, we should consider the consequences of alternative mutation rate estimates, as pedigree-based methods relying on variation from the most recent several centuries 8,10,28 may be more relevant. The pedigree-based estimate from the largest set of mutations 8 would lead to a decrease in expansion times by ~15%, increasing the precision of the correspondences proposed for E1b and R1a. For R1b, a 15% decrease would suggest an expansion postdating the Yamnaya migration, perhaps better explaining the distinction between the Yamnaya R1b chromosomes and the expanding R1b-L11 lineage.…”

“…The role of demography has risen to prominence with reports of male-specific bottlenecks in several geographical areas after 10 thousand years ago (kya) 5–7 , at times putatively associated with the spread of farming 5 or Bronze Age culture 6 . With improved calibration of the Y-SNV mutation rate 8–10 and, consequently, more secure dating of relevant features of the Y-chromosome phylogeny, it is now possible to hone such interpretations.…”

Great ape Y Chromosome and mitochondrial DNA phylogenies reflect subspecies structure and patterns of mating and dispersal

“…MSY-specific mutation rates for great apes are not available, so like others (Xue et al 2015), we have used the published human rate, here based on the observation of 609 MSY mutations in Icelandic pedigrees (Helgason et al 2015). A pedigree-based mutation study has been published based on chimpanzee autosomal sequences (Venn et al 2014), and this yields an overall rate closely matching the human rate.…”

“…In the absence of good estimates for great ape MSY mutation rates, we used the human rate of 3.07 (95% CI: 2.76-3.40) × 10 −8 mutations/nucleotide/generation (Helgason et al 2015). This was scaled according to the generation times (Langergraber et al 2012) for each species (bonobos [assumed] and chimpanzees: 24 yr; gorillas and orangutans: 20 yr; humans: 30 yr) to mutations/nucleotide/year.…”