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Published online on October 19, 2005, 10.1073/pnas.0505537102
PNAS | November 1, 2005 | vol. 102 | no. 44 | 15936-15941


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EVOLUTION
Evolutionary population genetics of promoters: Predicting binding sites and functional phylogenies

Ville Mustonen, and Michael Lässig *

Institut für Theoretische Physik, Universität zu Köln, Zülpicherstrasse 77, 50937 Cologne, Germany

Edited by Tomoko Ohta, National Institute of Genetics, Mishima, Japan and approved August 8, 2005 (received for review June 30, 2005)

We study the evolution of transcription factor-binding sites in prokaryotes, using an empirically grounded model with point mutations and genetic drift. Selection acts on the site sequence via its binding affinity to the corresponding transcription factor. Calibrating the model with populations of functional binding sites, we verify this form of selection and show that typical sites are under substantial selection pressure for functionality: for cAMP response protein sites in Escherichia coli, the product of fitness difference and effective population size takes values 2N{Delta}F of order 10. We apply this model to cross-species comparisons of binding sites in bacteria and obtain a prediction method for binding sites that uses evolutionary information in a quantitative way. At the same time, this method predicts the functional histories of orthologous sites in a phylogeny, evaluating the likelihood for conservation or loss or gain of function during evolution. We have performed, as an example, a cross-species analysis of E. coli, Salmonella typhimurium, and Yersinia pseudotuberculosis. Detailed lists of predicted sites and their functional phylogenies are available.

Author contributions: V.M. and M.L. designed research, performed research, analyzed data, and wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviation: CRP, cAMP response protein.

* To whom correspondence should be addressed. E-mail: lassig{at}thp.uni-koeln.de.

© 2005 by The National Academy of Sciences of the USA


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