From: ncbi-seminar-admin@ncbi.nlm.nih.gov on behalf of Eugene Koonin
[koonin@ncbi.nlm.nih.gov]
Sent: Monday, November 12, 2001 4:09 PM
To: ncbi-seminar@golem.nlm.nih.gov
Cc: k-makova@uchicago.edu
Subject: special seminar

Bldg. 38A, 5th floor conference room
Tuesday, Nov 20, 2 PM

Male-Driven Evolution Revisited

Kateryna Makova, University of Chicago

Early studies of human genetic diseases suggested a higher rate of mutation in
males than in females. Later, the male-to-female ratio (alpha) of mutation
rate was estimated from DNA sequence data to be ~4-6 in higher primates. Two
recent studies, however, claimed that alpha is only ~2 in humans. This is
smaller than not only all previous estimates in higher primates but also the
estimates of alpha > 4 in carnivores and birds; a is expected to be higher in
humans than in carnivores and birds because humans have a longer generation
time and a larger sex difference in the number of germ cell cycles. To resolve
this controversy, we sequenced a ~10.4 kb noncoding fragment on Y and its
homologous counterpart on chromosome 3 in human, greater apes, and lesser apes.
 Our estimate of alpha from the internal branches of the phylogeny is 5.25 (95%
CI: 2.27-53.38), similar to the previous estimates in primates, but
significantly higher than the two recent estimates. In contrast, for the
external (short, species-specific) branches, alpha is only 2.23 (95% CI:
1.41-3.79), similar to the two recent estimates. We suggest that it is often
inappropriate to use closely related species to estimate alpha, because of the
effect of ancient polymorphism on the estimation of branch lengths and because
of other factors. In particular, we provide an explanation for the small
estimates obtained in the two recent studies. In conclusion, our study
reinstates a high male-to-female ratio of mutation rate in hominoids and
supports the view that DNA replication errors are the primary source of germ
line mutation.

-- 
Eugene V. Koonin, PhD
National Center for Biotechnology Information
National Library of Medicine
National Institutes of Health, Bldg. 38A, Rm. 5N503 (5th floor)
8600 Rockville Pike
Bethesda, MD 20894, USA
Phone: (301)435-5913; Fax: (301)435-7794 or (301)480-9241
email koonin@ncbi.nlm.nih.gov
http://www.ncbi.nlm.nih.gov/CBBresearch/Koonin/