TY - JOUR
T1 - Strong male-driven evolution of DNA sequences in humans and apes
AU - Makova, Kateryna D.
AU - Li, Wen Hsiung
N1 - Funding Information:
The DNA samples were purchased from San Diego Zoological Society and the gibbon sample was given by M. Jensen-Seaman. We thank J. Crow and D. Page for comments. This study was supported by NIH grants.
PY - 2002/4/11
Y1 - 2002/4/11
N2 - Studies of human genetic diseases have suggested a higher mutation rate in males than in females and the male-to-female ratio (α) of mutation rate has been estimated from DNA sequence and microsatellite data to be about 4-6 in higher primates. Two recent studies, however, claim that α is only about 2 in humans. This is even smaller than the estimates (α > 4) for carnivores and birds; humans should have a higher α 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 α from the internal branches of the phylogeny is 5.25 (95% confidence interval (CI) 2.44 to ∞), similar to the previous estimates, but significantly higher than the two recent ones. In contrast, for the external (short, species-specific) branches, α is only 2.23 (95% CI: 1.47-3.84). We suggest that closely related species are not suitable for estimating α, because of ancient polymorphism and other factors. Moreover, we provide an explanation for the small estimate of α in a previous study. Our study reinstates a high α in hominoids and supports the view that DNA replication errors are the primary source of germline mutation.
AB - Studies of human genetic diseases have suggested a higher mutation rate in males than in females and the male-to-female ratio (α) of mutation rate has been estimated from DNA sequence and microsatellite data to be about 4-6 in higher primates. Two recent studies, however, claim that α is only about 2 in humans. This is even smaller than the estimates (α > 4) for carnivores and birds; humans should have a higher α 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 α from the internal branches of the phylogeny is 5.25 (95% confidence interval (CI) 2.44 to ∞), similar to the previous estimates, but significantly higher than the two recent ones. In contrast, for the external (short, species-specific) branches, α is only 2.23 (95% CI: 1.47-3.84). We suggest that closely related species are not suitable for estimating α, because of ancient polymorphism and other factors. Moreover, we provide an explanation for the small estimate of α in a previous study. Our study reinstates a high α in hominoids and supports the view that DNA replication errors are the primary source of germline mutation.
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U2 - 10.1038/416624a
DO - 10.1038/416624a
M3 - Article
C2 - 11948348
AN - SCOPUS:0037061501
SN - 0028-0836
VL - 416
SP - 624
EP - 626
JO - Nature
JF - Nature
IS - 6881
ER -