dorsal/arxiv
View SchemaOn the Selection and Evolution of Regulatory DNA Motifs
| Authors | Ulrich Gerland, Terence Hwa |
|---|---|
| Categories | |
| ArXiv ID | physics/0112039 |
| URL | https://arxiv.org/abs/physics/0112039 |
| Journal | J. Mol. Evol. 55 (2002) 386-400 |
Abstract
The mutation and selection of regulatory DNA sequences is 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.
{
"annotation_id": "459f0242-5e85-41c6-b6cd-3a7f1ef25280",
"date_created": "2026-03-02T18:00:39.219000Z",
"date_modified": "2026-03-02T18:00:39.219000Z",
"file_hash": "c2148d3913769a80a6efcfa45dca15792b65f92ee476d7e6da18201c186ebab6",
"private": false,
"record": {
"abstract": "The mutation and selection of regulatory DNA sequences is presented as an\nideal model system of molecular evolution where genotype, phenotype, and\nfitness can be explicitly and independently characterized. In this theoretical\nstudy, we construct an explicit model for the evolution of regulatory\nsequences, making use of the known biophysics of the binding of regulatory\nproteins to DNA sequences, under the assumption that fitness of a sequence\ndepends only on its binding affinity to the regulatory protein. The model is\nconfined to the mean field (i.e., infinite population size) limit. Using\nrealistic values for all parameters, we determine the minimum fitness advantage\nneeded to maintain a binding sequence, demonstrating explicitly the ``error\nthreshold\u0027\u0027 below which a binding sequence cannot survive the accumulated\neffect of mutation over long time. The commonly observed ``fuzziness\u0027\u0027 in\nbinding motifs arises naturally as a consequence of the balance between\nselection and mutation in our model. In addition, we devise a simple model for\nthe evolution of multiple binding sequences in a given regulatory region. We\nfind the number of evolutionarily stable binding sequences to increase in a\nstep-like fashion with increasing fitness advantage, if multiple regulatory\nproteins can synergistically enhance gene transcription. We discuss possible\nexperimental approaches to resolve open questions raised by our study.",
"arxiv_id": "physics/0112039",
"authors": [
"Ulrich Gerland",
"Terence Hwa"
],
"categories": [
"physics.bio-ph",
"cond-mat.stat-mech",
"q-bio.PE"
],
"journal_ref": "J. Mol. Evol. 55 (2002) 386-400",
"title": "On the Selection and Evolution of Regulatory DNA Motifs",
"url": "https://arxiv.org/abs/physics/0112039"
},
"schema_id": "dorsal/arxiv",
"source": {
"execution_id": "248714af-17ce-47da-bcd3-48316f63d7e5",
"id": "arXiv Dataset IDs",
"type": "Model",
"variant": "snapshot-2026-03-01",
"version": "0.1.0"
},
"user_id": 1000002
}