On the Selection and Evolution of Regulatory DNA Motifs (original) (raw)

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.

Access this article

Log in via an institution

Subscribe and save

• Get 10 units per month
• Download Article/Chapter or eBook
• 1 Unit = 1 Article or 1 Chapter
• Cancel anytime Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

1. Department of Physics, University of California, San Diego, La Jolla, CA 92093-0319, , , , , , US
   Ulrich Gerland & Terence Hwa

Authors

1. Ulrich Gerland
   You can also search for this author inPubMed Google Scholar
2. Terence Hwa
   You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Gerland, U., Hwa, T. On the Selection and Evolution of Regulatory DNA Motifs .J Mol Evol 55, 386–400 (2002). https://doi.org/10.1007/s00239-002-2335-z

Download citation

• Received: 10 September 2001
• Accepted: 02 April 2002
• Issue Date: October 2002
• DOI: https://doi.org/10.1007/s00239-002-2335-z

Keywords