Author SummaryCells use sophisticated regulation to transform static genomic information into flexible function. We are still far from understanding how such regulation evolves. Short DNA sequences that physically bind transcription factors in promoter areas near target genes play an important role in gene regulation and are directly subject to mutation and selection. In this work, we develop a methodology for studying the evolution of promoter sequences under the effect of multiple regulatory interactions. We present a model that describes the evolutionary process at each genomic locus, taking into account a random flux of mutations that occur in it and the effects of transcription factor binding sites gain or loss. Our model accounts for dependencies (or epistasis) between adjacent loci that contribute to the same regulatory interactions: mutation in one such locus immediately changes the effect of mutations in the other. Using our model, we characterize the evolution of promoters in yeast, showing that many regulatory interactions that were discovered experimentally or computationally are evolutionarily unstable. The dynamic nature of transcriptional interactions may be explained if the regulatory phenotype is achieved through multiple interactions at different levels of specificity, and if only relatively few of these interactions are essential for themselves.
Search
Reviews
[Write a review of this article]
Find related articles from these CiteULike users
