MBE Advance Access published online on March 10, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh105
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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1 Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, NG7 2UH, United Kingdom
* To whom correspondence should be addressed. E-mail: john.brookfield{at}nottingham.ac.uk.
The evolution of new functions takes place partially through changes in the way transcription is controlled. Transcriptional control is brought about by the interactions of transcription factors with short target motifs in the DNAs of promoters and enhancers. One way in which changes in gene expression can evolve is through the acquisition of new transcription factor targets in enhancer sequences. Since such target sites are simple, they can be produced rapidly from random DNA by mutation and selection. Here we consider a population of organisms that finds itself in an ecological situation where bringing a particular target gene under the control of a particular transcription factor would be favoured by natural selection. We ask what will be the time required for such a process, as a function of the selection for the new target, the mutation rate, and the population size. The starting sequences considered are either real enhancers from the Drosophila melanogaster genome, or randomised versions of these. We find that the time required to find binding sites is strongly dependent on the existence in the starting sequence of sites that differ from binding sites by single substitutions (pre-sites). The process of converting pre-sites to binding sites is driven by natural selection and thus the time required typically reduces with the strength of selection. However, if there is a strongly distorted G: C ratio in the starting sequence, pre-sites will typically be absent, and the finding of binding sites will be preceded by a long time period of neutral evolution, however strong is the selection favouring sites. The positions of pre-sites largely determine where binding sites will evolve. One result of this that any incremental selective benefits that result from the relative positioning of sites have a surprisingly small impact on the final binding site positions. Key Words:
Enhancers, evolution, Drosophila
© 2004 Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved.
Original Articles
Expected Rates and Modes of Evolution of Enhancer Sequences
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