Unexpectedly similar rates of nucleotide substitution found in male and female hominids

In 1947, it was suggested that, in humans, the mutation rate is dramaticall y higher in the male germ line than in the female germ line(1). This hypoth esis has been supported by the observation that, among primates, Y-linked g enes evolved more rapidly than homologous X-linked genes(2-6). Based on the se evolutionary studies, the ratio (alpha(m)) of male to female mutation ra tes in primates was estimated to be about 5. However, selection could have skewed sequence evolution in introns and exons(7-10). In addition, some of the X-Y gene pairs studied lie within chromosomal regions with substantiall y divergent nucleotide sequences(7,11,12). Here we directly compare human X and Y sequences within a large region with no known genes. Here the two ch romosomes are 99% identical, and X-Y divergence began only three or four mi llion years ago, during hominid evolution(13-15). In apes, homologous seque nces exist only on the X chromosome. We sequenced and compared 38.6 kb of t his region from human X, human Y, chimpanzee X and gorilla X chromosomes. W e calculated alpha(m) to be 1.7 (95% confidence interval 1.15-2.87), signif icantly lower than previous estimates in primates. We infer that, in humans and their immediate ancestors, male and female mutation rates were far mor e similar than previously supposed.