EVIDENCE FOR A SELECTIVELY FAVORABLE REDUCTION IN THE MUTATION-RATE OF THE X-CHROMOSOME

The equilibrium per-genome mutation rate in sexual species is thought to result from a trade-off between the benefits of reducing the delete rious mutation rate and the costs of increasing fidelity(1,2). We prop ose that selection will often favour a lower mutation rate on the X ch romosome than on autosomes, owing to the exposure of deleterious reces sive mutations on hemizygous chromosomes. We tested this hypothesis by examining 33 X-linked genes that have been sequenced in both mouse an d rat, and compared their rate of evolution against 238 autosomal gene s. The X-linked genes were found to have a significantly lower rate of synonymous substitution than the autosomal genes. Neither the suppose d higher mutation rate in males nor stronger purifying selection again st slightly deleterious mutations on the X chromosome can account for the low value. The most parsimonious explanation is that rodents have a lower mutation rate on the X chromosome than on autosomes. It is the refore likely that previous indirect estimates of the excess male muta tion rate are inaccurate. Indeed, after correction we find no evidence for a male-biased mutation rate in rodents. Furthermore, the rate of synonymous substitution in Y-linked genes is not significantly differe nt from that in autosomal ones. The extent to which enhanced male muta tion rates are problematic(3) for the mutational deterministic model(4 ) of the evolution of sex must, in turn, be questioned.