ArticleCell reports2015
Systems-level response to point mutations in a core metabolic enzyme modulates genotype-phenotype relationship.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Metabolite correlation networks reveal complex phenotypes of adaptation-driving mutations.Nature communications · 2026Article
- Deciphering the Impact of Temperature on Pleiotropic Consequences of RNA Polymerase Mutations.Molecular biology and evolution · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- Genotype sampling for deep-learning assisted experimental mapping of a combinatorially complete fitness landscape.Bioinformatics (Oxford, England) · 2024Article
- Empowering drug off-target discovery with metabolic and structural analysis.Nature communications · 2023Article
- Growth-mediated negative feedback shapes quantitative antibiotic response.Molecular systems biology · 2022Article
- Avoidance of protein unfolding constrains protein stability in long-term evolution.Biophysical journal · 2021Article
- Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype.Molecular systems biology · 2021Article
- Restoration of fitness lost due to dysregulation of the pyruvate dehydrogenase complex is triggered by ribosomal binding site modifications.Cell reports · 2021Article
- Suboptimal Global Transcriptional Response Increases the Harmful Effects of Loss-of-Function Mutations.Molecular biology and evolution · 2021Article
- Fine-tuning ethanol oxidation pathway enzymes and cofactor PQQ coordinates the conflict between fitness and acetic acid production by Acetobacter pasteurianus.Microbial biotechnology · 2021Article
- Article
- Collateral fitness effects of mutations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Chromosomal barcoding of E. coli populations reveals lineage diversity dynamics at high resolution.Nature ecology & evolution · 2020Article
- Article
- Chimeric dihydrofolate reductases display properties of modularity and biophysical diversity.Protein science : a publication of the Protein Society · 2019Article
- Repeated Phenotypic Evolution by Different Genetic Routes in Pseudomonas fluorescens SBW25.Molecular biology and evolution · 2019Article
- Thermosensitivity of growth is determined by chaperone-mediated proteome reallocation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Ligand-promoted protein folding by biased kinetic partitioning.Nature chemical biology · 2017Article
- Bridging the physical scales in evolutionary biology: from protein sequence space to fitness of organisms and populations.Current opinion in structural biology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Linking the molecular effects of mutations to fitness is central to understanding evolutionary dynamics. Here, we establish a quantitative relation between the global effect of mutations on the E. coli proteome and bacterial fitness. We created E. coli strains with specific destabilizing mutations in the chromosomal folA gene encoding dihydrofolate reductase (DHFR) and quantified the ensuing changes in the abundances of 2,000+ E. coli proteins in mutant strains using tandem mass tags with subsequent LC-MS/MS. mRNA abundances in the same E. coli strains were also quantified. The proteomic effects of mutations in DHFR are quantitatively linked to phenotype: the SDs of the distributions of logarithms of relative (to WT) protein abundances anticorrelate with bacterial growth rates. Proteomes hierarchically cluster first by media conditions, and within each condition, by the severity of the perturbation to DHFR function. These results highlight the importance of a systems-level layer in the genotype-phenotype relationship.
Indexed as
Identifiers
What OpenQuestion holds
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.