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MBE Advance Access published online on March 25, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn072
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

Fast Evolution of Core Promoters in Primate Genomes

Han Liang, Yeong-Shin Lin# and Wen-Hsiung Li*

Department of Ecology and Evolution, University of Chicago, 1101 East 57th Street, Chicago, IL, 60637, USA
# Current address: Institute of Bioinformatics, National Chiao Tung University, Hsinchu, Taiwan 300

* To whom correspondence should be addressed, E-mail: whli{at}uchicago.edu, Telephone: 773-702-3104, Fax: 773-702-9740

Received for publication March 13, 2008. Accepted for publication March 18, 2008.

Despite much interest in regulatory evolution, how promoters have evolved remains poorly studied, mainly owing to paucity of data on promoter regions. Using a new set of high-quality experimentally determined core promoters of the human genome, we conducted a comparative analysis of 2,492 human and rhesus macaque promoters and their neighboring nearly-neutral regions. We found that the core promoters have an average rate of nucleotide substitution substantially higher than that at four-fold degenerate sites and only slightly lower than that for the assumed neutral controls of neighboring non-coding regions, suggesting that core promoters are subject to very weak selective constraints. Interestingly, we identified 24 core promoters (at false discovery rate = 50%) that have evolved at an accelerated rate compared to the neutral controls, suggesting that they may have undergone positive selection. The inferred positively selected genes show strong bias in molecular function. We also used population genetic approaches to examine the evolution of core promoters in human populations and found evidence of positive selection at some loci. Taken together, our results suggest that positive selection has played a substantial role in the evolution of transcriptional regulation in primates.

Key Words: regulatory evolution • substitution rate • positive selection • primate evolution • hitchhiking


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[Abstract] [Full Text] [PDF]


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