1. Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, Illinois 60637, USA

Correspondence to: Wen-Hsiung Li Correspondence and requests for materials should be addressed to W.-H.L. (e-mail: Email: whli@uchicago.edu).

Abstract

Studies of human genetic diseases have suggested a higher mutation rate in males than in females¹ and the male-to-female ratio () of mutation rate has been estimated from DNA sequence and microsatellite data to be about 4–6 in higher primates^{2, 3, 4, 5}. Two recent studies, however, claim that is only about 2 in humans^{6, 7}. This is even smaller than the estimates ( > 4) for carnivores and birds^{8, 9}; humans should have a higher than carnivores and birds because of a longer generation time and a larger sex difference in the number of germ cell cycles. To resolve this issue, we sequenced a noncoding fragment on Y of about 10.4 kilobases (kb) and a homologous region on chromosome 3 in humans, greater apes, and lesser apes. Here we show that our estimate of from the internal branches of the phylogeny is 5.25 (95% confidence interval (CI) 2.44 to ), similar to the previous estimates^{2, 3, 4, 5}, but significantly higher than the two recent ones^{6, 7}. In contrast, for the external (short, species-specific) branches, is only 2.23 (95% CI: 1.47–3.84). We suggest that closely related species are not suitable for estimating , because of ancient polymorphism and other factors. Moreover, we provide an explanation for the small estimate of in a previous study¹². Our study reinstates a high in hominoids and supports the view that DNA replication errors are the primary source of germline mutation.