Timing of ancient human Y lineage depends on the mutation rate: A comment on Mendez et al

2 Letter Mendez et al. 1 recently report the identification of a Y chromosome lineage from an African American that is an outgroup to all other known Y haplotypes, and report a time to most recent common ancestor, TMRCA, for human Y lineages that is substantially longer than any previous estimate 2-4. The identification of a novel Y haplotype is always exciting, and this haplotype, in particular, is unique in its basal position on the Y haplotype tree. However, at 338 (237-581) thousand years ago, kya, the extremely ancient TMRCA reported by Mendez et al. 1 is inconsistent with the known human fossil record (which estimate the age of anatomically modern humans at 195 +-5 kya 5), with estimates from mtDNA (176.6 +-11.3 kya 6 , and 204.9 (116.8-295.7) kya 7) and with population genetic theory. The inflated TMRCA can quite easily be attributed to the extremely low Y chromosome mutation rate used by the authors 1. The mutation rate is not identical across chromosome types. Male mutation bias refers to the higher rate of mutation in the male lineage versus the female lineage, and is thought to result primarily from the higher number of rounds of replication in the male germline relative to the female germline 8; 9. Because the Y chromosome is present only in the male germline, its mutation rate is expected to reflect the male mutation rate, while the mutation rate on the autosomes, present half of the time in the male germline, and half of the time in the female germline, should reflect the sex-average mutation rate 9. The magnitude of male mutation bias increases with increasing generation time 10. In humans, specifically, the relevance of male mutation bias is manifest in the increasing mutation rate observed with increasing paternal age 11. Mendez et al. 1 , assuming there is a direct adjustment for the male-specific mutation bias, derive an estimate of 6.17x10-10 mutations/nucleotide/year (range: 4.39x10-10 – 7.07x10-10) on the Y chromosome, assuming a median of 30 years per generation, using only information about autosomal substitution rates 11. But, recent work, comparing estimates of male mutation bias using different chromosome comparisons (X/Autosome, Y/Autosome, X/Y), have shown that while male mutation bias may explain most of the differences in the mutation rates between each sex chromosome and the autosomes, it cannot account for all of the rate variation 10; 12. Thus, estimates of the mutation rate …