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Studying the evolution of promoter sequences : a waiting time problem

MPG-Autoren
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Behrens,  Sarah
Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Vingron,  Martin
Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Behrens, S., & Vingron, M. (2010). Studying the evolution of promoter sequences: a waiting time problem. Journal Computational Biology, 17(12), 1591-1606. doi:10.1089/cmb.2010.0084.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0010-79CD-B
Zusammenfassung
To gain a better understanding of the evolutionary dynamics of regulatory DNA sequences, we address the following questions: (1) How long does it take until a given transcription factor (TF) binding site emerges at random in a promoter sequence? and (2) How does the composition of a TF binding site affect this waiting time? Using two different probabilistic models (an i.i.d. model and a neighbor dependent model), we can compute the expected waiting time for every k-mer, k ranging from 5 to 10, until it appears in a promoter of a species. Our findings indicate that new TF binding sites can be created on a short evolutionary time scale, i.e. in a time span below the speciation time of human and chimp. Furthermore, one can conclude that the composition of a TF binding site plays a crucial role concerning the waiting time until it appears and that the CpG methylation-deamination substitution process probably accelerates the creation of new TF binding sites. A screening of existing TF binding sites moreover reveals that k-mers predicted to have short waiting times occur more frequently than others.