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Biophysical Fitness Landscapes for Transcription Factor Binding Sites

Allan Haldane, Michael Manhart, Alexandre V. Morozov, Sheng Zhong
2014 PLoS Computational Biology  
Using an evolutionary model for monomorphic populations evolving on a fitness landscape, we infer fitness as a function of TF-DNA binding energy for a collection of 12 yeast TFs, and show that the shape  ...  We find little statistical support for the fitness landscape in which each position in the binding site evolves independently, showing that epistasis is common in evolution of gene regulation.  ...  Gene activation and repression are mediated by binding of transcription factors (TFs) to their cognate genomic sites.  ... 
doi:10.1371/journal.pcbi.1003683 pmid:25010228 pmcid:PMC4091707 fatcat:gont6a5wkjduldwhlckrctpnxe

Fitness landscape for nucleosome positioning

D. Weghorn, M. Lassig
2013 Proceedings of the National Academy of Sciences of the United States of America  
To infer regulatory binding sites in the yeast genome, we use standard statistical models of the position-dependent binding energy profile for specific transcription factors (22).  ...  Here, we derive a fitness landscape for intergenic DNA segments in yeast as a function of two molecular phenotypes: their elasticity-dependent histone affinity and their coverage with transcription factor  ...  We thank Alain Arneodo for providing the sequencebased algorithm to compute histone binding energies and nucleosome occupancy (28) and Stephan Schiffels for kindly making his Wright-Fisher evolution  ... 
doi:10.1073/pnas.1210887110 pmid:23784778 pmcid:PMC3704022 fatcat:oonvlg4smjf47hh7iojh2qjkxi

Why Transcription Factor Binding Sites Are Ten Nucleotides Long

A. J. Stewart, S. Hannenhalli, J. B. Plotkin
2012 Genetics  
Gene expression is controlled primarily by transcription factors, whose DNA binding sites are typically 10 nt long.  ...  as between the number of targets a transcription factor regulates and the information content in its binding sites.  ...  By specifying binding site fitness in terms of binding energy, these models are able to reconstruct quantitative fitness landscapes that can be used to study the evolution of transcription regulation.  ... 
doi:10.1534/genetics.112.143370 pmid:22887818 pmcid:PMC3522170 fatcat:vb7dbn4kandkfh7pbebgvfebia

Energy-dependent fitness: A quantitative model for the evolution of yeast transcription factor binding sites

V. Mustonen, J. Kinney, C. G. Callan, M. Lassig
2008 Proceedings of the National Academy of Sciences of the United States of America  
Our model for binding site evolution is founded on biophysics: the binding energy between transcription factor and site is a quantitative phenotype of regulatory function, and selection is given by a fitness  ...  We present a genomewide cross-species analysis of regulation for broad-acting transcription factors in yeast.  ...  We thank the Kavli Institute for Theoretical Physics for their hospitality.  ... 
doi:10.1073/pnas.0805909105 pmid:18723669 pmcid:PMC2527919 fatcat:lgbic4ynxfdlneicpfc55brasm

Adaptive evolution of transcription factor binding sites

Johannes Berg, Stana Willmann, Michael Lässig
2004 BMC Evolutionary Biology  
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.  ...  We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations.  ...  Tautz for interesting discussions, and to P. Arndt and U. Gerland for a critical reading of the manuscript. This work has been supported by DFG grant LA 1337/1-1.  ... 
doi:10.1186/1471-2148-4-42 pmid:15511291 pmcid:PMC535555 fatcat:3xrpep73mnggdj4lks557b65ci

Adaptive evolution of transcription factor binding sites [article]

Johannes Berg, Stana Willmann, Michael Lässig
2004 arXiv   pre-print
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.  ...  We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations.  ...  Tautz for interesting discussions, and to P. Arndt and U. Gerland for a critical reading of the manuscript. This work has been supported by DFG grant LA 1337/1-1.  ... 
arXiv:cond-mat/0301574v2 fatcat:tgljxhhlwrhzzk7fyxn57aujby

Dynamics of Transcription Factor Binding Site Evolution

Murat Tuğrul, Tiago Paixão, Nicholas H. Barton, Gašper Tkačik, Justin C. Fay
2015 PLoS Genetics  
We use a biophysical model for directional selection on gene expression to estimate the rates of gain and loss of transcription factor binding sites (TFBS) in finite populations under both point and insertion  ...  The availability of longer regulatory sequences in which multiple binding sites can evolve simultaneously, the presence of "pre-sites" or partially decayed old sites in the initial sequence, and biophysical  ...  Acknowledgments We thank Magdalena Steinrück, Georg Rieckh, Ferran Palero and Ziya Kalay for helpful comments. Author Contributions  ... 
doi:10.1371/journal.pgen.1005639 pmid:26545200 pmcid:PMC4636380 fatcat:3gso7ukaerb23lunh7nrqzrdza

Genotype to Phenotype Mapping and the Fitness Landscape of the E. coli lac Promoter

Jakub Otwinowski, Ilya Nemenman, Andrew J. Yates
2013 PLoS ONE  
We identify transcription factor (CRP) and RNA polymerase binding sites in the promotor region and their interactions without difficult optimization steps.  ...  for the full mutagenized sequence and about 15% for the subsequence associated with protein binding sites.  ...  Johnson for commenting on the manuscript, and Bruce Levine for general guidance.  ... 
doi:10.1371/journal.pone.0061570 pmid:23650500 pmcid:PMC3641078 fatcat:5csxgukswzaahajxksn6gaszji

Evolution of new regulatory functions on biophysically realistic fitness landscapes

Tamar Friedlander, Roshan Prizak, Nicholas H. Barton, Gašper Tkačik
2017 Nature Communications  
In contrast, we study the elementary step in the evolution of gene regulatory networks: duplication of a transcription factor followed by selection for TFs to specialize their inputs as well as the regulation  ...  We show how to coarse grain the complete, biophysically realistic genotype-phenotype map for this process into macroscopic functional outcomes and quantify the probability of attaining each.  ...  In our model, n TF transcription factors regulate n G genes by binding to sites of length L base pairs; for simplicity, we consider each gene to have one such binding site.  ... 
doi:10.1038/s41467-017-00238-8 pmid:28790313 pmcid:PMC5548793 fatcat:z3dwfkwvv5frvf4mn2d7kvmuqq

On the incongruence of genotype-phenotype and fitness landscapes [article]

Malvika Srivastava, Joshua L. Payne
2022 bioRxiv   pre-print
Here, we use theoretical models and empirical data on transcription factor-DNA interactions to systematically study the incongruence of genotype-phenotype and fitness landscapes when selection favors a  ...  Yet, genotype-phenotype landscapes are often used as a proxy for fitness landscapes to study the dynamics and predictability of evolution.  ...  McCandlish for discussions.  ... 
doi:10.1101/2022.02.01.478629 fatcat:znx4xx2rdbahxhptvmzng4guhi

From Biophysics to Evolutionary Genetics: Statistical Aspects of Gene Regulation [chapter]

Michael Lässig
2007 Structural Approaches to Sequence Evolution  
In particular, we infer fitness landscapes of binding sites from genomic data, leading to a quantitative evolutionary picture of regulation.  ...  Transcriptional interactions involve the binding of proteins to regulatory DNA.  ...  After projection onto the energy, the fitness landscape 2NF(E) for CRP binding sites is thus given by fig. 4(b) [16] .  ... 
doi:10.1007/978-3-540-35306-5_12 fatcat:cuhqth76draczmnaslpsyjgk3y

From biophysics to evolutionary genetics: statistical aspects of gene regulation

Michael Lässig
2007 BMC Bioinformatics  
In particular, we infer fitness landscapes of binding sites from genomic data, leading to a quantitative evolutionary picture of regulation.  ...  Transcriptional interactions involve the binding of proteins to regulatory DNA.  ...  After projection onto the energy, the fitness landscape 2NF(E) for CRP binding sites is thus given by fig. 4(b) [16] .  ... 
doi:10.1186/1471-2105-8-s6-s7 pmid:17903288 pmcid:PMC1995540 fatcat:uc7d36cm7fforb6pjxjfryliqa

Bridging the physical scales in evolutionary biology: from protein sequence space to fitness of organisms and populations

Shimon Bershtein, Adrian WR Serohijos, Eugene I Shakhnovich
2017 Current Opinion in Structural Biology  
Highlights Biophysical fitness landscapes (BFL) map fitness to molecular and system-level traits BFL of a bacterial enzyme provides accurate prediction of antibiotic resistance Protein quality control  ...  Bridging the gap between the molecular properties of proteins and organismal/population fitness is essential for understanding evolutionary processes.  ...  We are grateful to members of Shakhnovich lab for numerous discussions and help and to Michael Manhart and William Jacobs for critical reading of the manuscript and helpful suggestions.  ... 
doi:10.1016/j.sbi.2016.10.013 pmid:27810574 pmcid:PMC5373997 fatcat:ljk77l5nhvfmrb23mzffscaa2y

A simple biophysical model predicts more rapid accumulation of hybrid incompatibilities in small populations [article]

Bhavin S. Khatri, Richard A. Goldstein
2015 arXiv   pre-print
Here, we examine a biophysical model of speciation based on the binding of a protein transcription factor to a DNA binding site, and how their independent co-evolution, in a stabilizing landscape, of two  ...  The biophysical model thus represents a robust mechanism of rapid reproductive isolation for small populations and large sequences, that does not require peak-shifts or positive selection.  ...  METHODS Quaternary Model of Transcription Factor-DNA Binding The two-state approximation [42, 43] for transcription factor binding assumes that amino acid nucleotide interactions are either optimal  ... 
arXiv:1503.07794v1 fatcat:uajbbswktbcwxbfnjofq6yysu4

The evolution of complex gene regulation by low-specificity binding sites

A. J. Stewart, J. B. Plotkin
2013 Proceedings of the Royal Society of London. Biological Sciences  
Transcription factor binding sites vary in their specificity, both within and between species.  ...  Likewise, our results also help to explain the well-known trend towards lower specificity in the transcription factor binding sites of higher eukaryotes, which perform complex regulatory tasks, compared  ...  We thank Sridhar Hannenhalli, the Plotkin laboratory and two anonymous referees for constructive input, as well as C. Bergman for tweeting helpful references.  ... 
doi:10.1098/rspb.2013.1313 pmid:23945682 pmcid:PMC3757967 fatcat:7mo2it4wc5eu3j6ox4p45rcrf4
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