Studying the evolution of promoter sequences: a waiting time problem.
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. Supplementary Material is available at www.libertonline.com/cmb .
Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany. sbehrens@molgen.mpg.de
Sarah
S
Behrens
Martin
M
Vingron
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D030561:Databases, Nucleic Acid; D019143:Evolution, Molecular; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013997:Time Factors; D014157:Transcription Factors
D014157:Transcription Factors