Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 44, Pages 15936-15941Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0505537102
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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.
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