MALE-DRIVEN EVOLUTION OF DNA-SEQUENCES

IT is commonly believed1,2 that the mutation rate is much higher in the human male germ line than in the female germ line because the number of germ-cell divisions per generation is much larger in males than in females. But direct estimation of mutation rates is difficult, relying mainly on sex-linked genetic diseases3, so the ratio (alpha(m)) of male to female mutation rates is not clear. It has been noted4 that if alpha(m). is very large, then the rate of synonymous substitution in X-linked genes should be only 2/3 of that in autosomal genes, and comparison of human and rodent genes supported this prediction4. As the number of X-linked genes used in the study was small and the X-linked and autosomal sequences were non-homologous, and given that the synonymous rate varies among genes5, we sequenced the last intron (approximately 1 kb) of the Y-linked and X-linked zinc-finger-protein genes (ZFY and ZFX) in humans, orang-utans, baboons and squirrel monkeys. The ratio Y/X of the substitution rate in the Y-linked intron to that in the X-linked intron is approximately 2.3, which is close to that estimated from synonymous rates in the ZFY and ZFX genes6-8 and implies alpha(m) almost-equal-to 6. This estimate of alpha(m) supports the view that the evolution of DNA sequences in higher primates is male-driven. It is, however, much lower than the previous estimate4 and therefore raises a number of issues.