On the selection and evolution of regulatory DNA motifs

Ulrich Gerland, Terence Hwa

Research output: Contribution to journalArticlepeer-review

85 Scopus citations


The mutation and selection of regulatory DNA sequences are presented as an ideal model system of molecular evolution where genotype, phenotype, and fitness can be explicitly and independently characterized. In this theoretical study, we construct an explicit model for the evolution of regulatory sequences, making use of the known biophysics of the binding of regulatory proteins to DNA sequences, under the assumption that fitness of a sequence depends only on its binding affinity to the regulatory protein. The model is confined to the mean field (i.e., infinite population size) limit. Using realistic values for all parameters, we determine the minimum fitness advantage needed to maintain a binding sequence, demonstrating explicitly the "error threshold" below which a binding sequence cannot survive the accumulated effect of mutation over long time. The commonly observed "fuzziness" in binding motifs arises naturally as a consequence of the balance between selection and mutation in our model. In addition, we devise a simple model for the evolution of multiple binding sequences in a given regulatory region. We find the number of evolutionarily stable binding sequences to increase in a step-like fashion with increasing fitness advantage, if multiple regulatory proteins can synergistically enhance gene transcription. We discuss possible experimental approaches to resolve open questions raised by our study.

Original languageEnglish
Pages (from-to)386-400
Number of pages15
JournalJournal of Molecular Evolution
Issue number4
StatePublished - 1 Oct 2002
Externally publishedYes


  • Error threshold
  • Mutation-selection model
  • Regulatory sequences
  • Transcription regulation


Dive into the research topics of 'On the selection and evolution of regulatory DNA motifs'. Together they form a unique fingerprint.

Cite this