The male-to-female ratio of mutation rate, α, has been estimated to be 6 using the last intron sequences of the ZFX and ZFY genes in 4 species of higher primates (Shimmin 1993b). This estimate has a very large 95% confidence interval (from 2 to 84) and cannot exclude the possibility that a is very large as suggested by Miyata et al. (1987). To obtain a more reliable estimate, Polymerase Chain Reaction (PCR) was used to amplify and sequence the last introns of the ZFX/ZFY genes in two additional primate species (the colobus monkey and tamarin). We analyzed these and the homologous sequences for 4 other primate species - a total of 12 introns across 6 primate species. Again, an estimate of α = 6 was obtained, but the 95% confidence interval was reduced to (3, 33). Two introns (A and B) of another pair of genes, SMCX and SMCY, in 4 species of primates were also amplified and sequenced. From intron A sequences, a was estimated to be 4.2 with a 95% confidence interval from 2.2 to 10.0. From intron B sequences, a was estimated to be 12.3 with a large 95% confidence interval (2.8, ∞); this estimate is not reliable because of the small size of the Y-linked intron B (-418 base pairs). Because the α estimates derived independently from different regions Of the genome (ZFX/ZFY and SMCX/SMCY) are close to each other and are also close to the sex ratio of the number of germ-cell divisions, c, in humans (-6), we conclude that substitution mutation in primate germ cells is largely replication dependent. Other possible factors that may contribute to a higher mutation rate in males and the implication of this study on the molecular clock hypothesis are discussed.
Substitution mutation, Mutagenesis, SMCX/SMCY, ZFX/ZFY, Primates
