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Adaptive evolution of transcription factor binding sites

BACKGROUND: The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks....

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Autores principales: Berg, Johannes, Willmann, Stana, Lässig, Michael
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535555/
https://www.ncbi.nlm.nih.gov/pubmed/15511291
http://dx.doi.org/10.1186/1471-2148-4-42
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author Berg, Johannes
Willmann, Stana
Lässig, Michael
author_facet Berg, Johannes
Willmann, Stana
Lässig, Michael
author_sort Berg, Johannes
collection PubMed
description BACKGROUND: The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. RESULTS: We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background) mutation rate, the selection coefficient, and the effective population size. CONCLUSIONS: The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.
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spelling pubmed-5355552004-12-12 Adaptive evolution of transcription factor binding sites Berg, Johannes Willmann, Stana Lässig, Michael BMC Evol Biol Research Article BACKGROUND: The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. RESULTS: We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background) mutation rate, the selection coefficient, and the effective population size. CONCLUSIONS: The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed. BioMed Central 2004-10-28 /pmc/articles/PMC535555/ /pubmed/15511291 http://dx.doi.org/10.1186/1471-2148-4-42 Text en Copyright © 2004 Berg et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Berg, Johannes
Willmann, Stana
Lässig, Michael
Adaptive evolution of transcription factor binding sites
title Adaptive evolution of transcription factor binding sites
title_full Adaptive evolution of transcription factor binding sites
title_fullStr Adaptive evolution of transcription factor binding sites
title_full_unstemmed Adaptive evolution of transcription factor binding sites
title_short Adaptive evolution of transcription factor binding sites
title_sort adaptive evolution of transcription factor binding sites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535555/
https://www.ncbi.nlm.nih.gov/pubmed/15511291
http://dx.doi.org/10.1186/1471-2148-4-42
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