ArticleeLife2015
Intermolecular epistasis shaped the function and evolution of an ancient transcription factor and its DNA binding sites.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
63 citing papers in PubMed, 114 citations in OpenAlex.
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Evolutionary pathways in epistatic mechanical networks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Epistatic contributions to human traits via transcription factor mechanisms.medRxiv : the preprint server for health sciences · 2025Article
- The structure of an ancient genotype-phenotype map shaped the functional evolution of a protein family.Nature ecology & evolution · 2025Article
- The structure of an ancient genotype-phenotype map shaped the functional evolution of a protein family.bioRxiv : the preprint server for biology · 2025Article
- A conserved ARF-DNA interface underlies auxin-triggered transcriptional response.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interpreting the CTCF-mediated sequence grammar of genome folding with AkitaV2.PLoS computational biology · 2025Article
- Highly multiplexed design of an allosteric transcription factor to sense new ligands.Nature communications · 2024Article
- The simplicity of protein sequence-function relationships.Nature communications · 2024Article
- Article
- Highly multiplexed design of an allosteric transcription factor to sense novel ligands.bioRxiv : the preprint server for biology · 2024Article
- Rugged fitness landscapes minimize promiscuity in the evolution of transcriptional repressors.Cell systems · 2024Article
- The simplicity of protein sequence-function relationships.bioRxiv : the preprint server for biology · 2024Article
- Evolution shapes interaction patterns for epistasis and specific protein binding in a two-component signaling system.Communications chemistry · 2024Article
- Article
- Epistasis and pleiotropy shape biophysical protein subspaces associated with drug resistance.Physical review. E · 2023Article
- Environment-dependent epistasis increases phenotypic diversity in gene regulatory networks.Science advances · 2023Article
- Robustness and innovation in synthetic genotype networks.Nature communications · 2023Article
- Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance.bioRxiv : the preprint server for biology · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Complexes of specifically interacting molecules, such as transcription factor proteins (TFs) and the DNA response elements (REs) they recognize, control most biological processes, but little is known concerning the functional and evolutionary effects of epistatic interactions across molecular interfaces. We experimentally characterized all combinations of genotypes in the joint protein-DNA sequence space defined by an historical transition in TF-RE specificity that occurred some 500 million years ago in the DNA-binding domain of an ancient steroid hormone receptor. We found that rampant epistasis within and between the two molecules was essential to specific TF-RE recognition and to the evolution of a novel TF-RE complex with unique derived specificity. Permissive and restrictive epistatic mutations across the TF-RE interface opened and closed potential evolutionary paths accessible by the other, making the evolution of each molecule contingent on its partner's history and allowing a molecular complex with novel specificity to evolve.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.