Male-driven evolution of DNA sequences

Abstract

IT is commonly believed^1,2 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 (α_m) of male to female mutation rates is not clear. It has been noted⁴ that if α_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 (~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 ~2.3, which is close to that estimated from synonymous rates in the ZFY and ZFX genes^6–8 and implies α_m≈6. This estimate of α_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.