ArticleCell reports2014
Negative feedback in genetic circuits confers evolutionary resilience and capacitance.
Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 33 citations in OpenAlex.
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Tuning evolvability via plasmid copy number and regulatory architecture.Nature communications · 2025Article
- Genetic controllers for enhancing the evolutionary longevity of synthetic gene circuits in bacteria.Nature communications · 2025Article
- Tuning Ultrasensitivity in Genetic Logic Gates Using Antisense RNA Feedback.ACS synthetic biology · 2025Article
- Mutation of self-binding sites in the promoter of the MrpC transcriptional regulator leads to asynchronousFrontiers in microbiology · 2023Article
- Adaptive evolvability through direct selection instead of indirect, second-order selection.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2022Review
- Genome interpretation using in silico predictors of variant impact.Human genetics · 2022Review
- Comparative transcriptome analysis identified important genes and regulatory pathways for flower color variation in Paphiopedilum hirsutissimum.BMC plant biology · 2021Article
- Single-molecule imaging of LexA degradation in Escherichia coli elucidates regulatory mechanisms and heterogeneity of the SOS response.Nature microbiology · 2021Article
- Genome-Wide Transcription Factor DNA Binding Sites and Gene Regulatory Networks inFrontiers in microbiology · 2021Article
- Multiscale effects of heating and cooling on genes and gene networks.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Synthetic negative feedback circuits using engineered small RNAs.Nucleic acids research · 2018Article
- NbGIS regulates glandular trichome initiation through GA signaling in tobacco.Plant molecular biology · 2018Article
- CRISPR-FRT targets shared sites in a knock-out collection for off-the-shelf genome editing.Nature communications · 2018Article
- Cooperativity of Negative Autoregulation Confers Increased Mutational Robustness.Physical review letters · 2016Article
- Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.PloS one · 2016Article
- Intramolecular phenotypic capacitance in a modular RNA molecule.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Natural selection for specific functions places limits upon the amino acid substitutions a protein can accept. Mechanisms that expand the range of tolerable amino acid substitutions include chaperones that can rescue destabilized proteins and additional stability-enhancing substitutions. Here, we present an alternative mechanism that is simple and uses a frequently encountered network motif. Computational and experimental evidence shows that the self-correcting, negative-feedback gene regulation motif increases repressor expression in response to deleterious mutations and thereby precisely restores repression of a target gene. Furthermore, this ability to rescue repressor function is observable across the Eubacteria kingdom through the greater accumulation of amino acid substitutions in negative-feedback transcription factors compared to genes they control. We propose that negative feedback represents a self-contained genetic canalization mechanism that preserves phenotype while permitting access to a wider range of functional genotypes.
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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.