ArticlePLoS computational biology2014
Biophysical fitness landscapes for transcription factor binding sites.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
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- Nonlinear regulatory dynamics of bacterial restriction-modification systems modulates horizontal gene transfer susceptibility.Nucleic acids research · 2025Article
- The highly rugged yet navigable regulatory landscape of the bacterial transcription factor TetR.Nature communications · 2024Article
- Insight into antioxidant-like activity and computational exploration of identified bioactive compounds in Talinum triangulare (Jacq.) aqueous extract as potential cholinesterase inhibitors.BMC complementary medicine and therapies · 2024Article
- On the incongruence of genotype-phenotype and fitness landscapes.PLoS computational biology · 2022Article
- Anticipating response function in gene regulatory networks.Journal of the Royal Society, Interface · 2021Article
- Unsupervised Inference of Protein Fitness Landscape from Deep Mutational Scan.Molecular biology and evolution · 2021Article
- The relation between crosstalk and gene regulation form revisited.PLoS computational biology · 2020Article
- cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel.Genome biology · 2020Article
- Biophysics and population size constrains speciation in an evolutionary model of developmental system drift.PLoS computational biology · 2019Article
- Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function.Molecular biology and evolution · 2018Article
- Comprehensive, high-resolution binding energy landscapes reveal context dependencies of transcription factor binding.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Strong epistatic and additive effects of linked candidate SNPs for Drosophila pigmentation have implications for analysis of genome-wide association studies results.Genome biology · 2017Article
- Accelerated simulation of evolutionary trajectories in origin-fixation models.Journal of the Royal Society, Interface · 2017Article
- Nucleotide Interdependency in Transcription Factor Binding Sites in the Drosophila Genome.Gene regulation and systems biology · 2016Article
- Simple Biophysical Model Predicts Faster Accumulation of Hybrid Incompatibilities in Small Populations Under Stabilizing Selection.Genetics · 2015Article
- Dynamics of Transcription Factor Binding Site Evolution.PLoS genetics · 2015Article
- A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate.Journal of theoretical biology · 2015Article
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3 authors.
Funding
Abstract
Phenotypic states and evolutionary trajectories available to cell populations are ultimately dictated by complex interactions among DNA, RNA, proteins, and other molecular species. Here we study how evolution of gene regulation in a single-cell eukaryote S. cerevisiae is affected by interactions between transcription factors (TFs) and their cognate DNA sites. Our study is informed by a comprehensive collection of genomic binding sites and high-throughput in vitro measurements of TF-DNA binding interactions. Using an evolutionary model for monomorphic populations evolving on a fitness landscape, we infer fitness as a function of TF-DNA binding to show that the shape of the inferred fitness functions is in broad agreement with a simple functional form inspired by a thermodynamic model of two-state TF-DNA binding. However, the effective parameters of the model are not always consistent with physical values, indicating selection pressures beyond the biophysical constraints imposed by TF-DNA interactions. We find little statistical support for the fitness landscape in which each position in the binding site evolves independently, indicating that epistasis is common in the evolution of gene regulation. Finally, by correlating TF-DNA binding energies with biological properties of the sites or the genes they regulate, we are able to rule out several scenarios of site-specific selection, under which binding sites of the same TF would experience different selection pressures depending on their position in the genome. These findings support the existence of universal fitness landscapes which shape evolution of all sites for a given TF, and whose properties are determined in part by the physics of protein-DNA interactions.
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