ArticleMolecular biology and evolution2009
Translationally optimal codons associate with structurally sensitive sites in proteins.
Article in Molecular biology and evolution, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers, 2 of them syntheses that pooled it.
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
127 citing papers in PubMed, 2 syntheses or guidelines pooled it, 222 citations in OpenAlex.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
- Predicting Functional Effects of Synonymous Variants: A Systematic Review and Perspectives.Frontiers in genetics · 2019Pooled it
- Transcripts enriched in codons that trigger P-site tRNA-mediated mRNA decay possess stable mRNA.FEBS open bio · 2026Article
- Comprehensive analysis of chloroplast genome evolution in Poaceae: codon usage patterns, selection pressures, and phylogenomic relationships.BMC genomics · 2026Article
- Functional synonymous mutations and their evolutionary consequences.Nature reviews. Genetics · 2025Review
- Translational fidelity and longevity are genetically linked.Nature communications · 2025Article
- Codon usage modulates the relationship between the burden and yield of protein overexpression.Journal of biological engineering · 2025Article
- CodonTransformer: a multispecies codon optimizer using context-aware neural networks.Nature communications · 2025Article
- The dynamics and functional impact of tRNA repertoires during early embryogenesis in zebrafish.The EMBO journal · 2024Article
- Compositional Features and Codon Usage Pattern of Genes Associated with Parkinson's Disease.Molecular neurobiology · 2024Article
- Differentially used codons among essential genes in bacteria identified by machine learning-based analysis.Molecular genetics and genomics : MGG · 2024Article
- Fitness benefits of a synonymous substitution in an ancient EF-Tu gene depend on the genetic background.Journal of bacteriology · 2024Article
- Synonymous codon usage regulates translation initiation.Cell reports · 2023Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Article
- satmut_utils: a simulation and variant calling package for multiplexed assays of variant effect.Genome biology · 2023Article
- Synonymous Codon Variant Analysis for Autophagic Genes Dysregulated in Neurodegeneration.Molecular neurobiology · 2023Article
- Evolution and codon usage bias of mitochondrial and nuclear genomes in Aspergillus section Flavi.G3 (Bethesda, Md.) · 2023Article
- Preferred synonymous codons are translated more accurately: Proteomic evidence, among-species variation, and mechanistic basis.Science advances · 2022Article
- Quantifying shifts in natural selection on codon usage between protein regions: a population genetics approach.BMC genomics · 2022Article
67 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 1 institution in 1 country.
Funding
Abstract
The mistranslation-induced protein misfolding hypothesis predicts that selection should prefer high-fidelity codons at sites at which translation errors are structurally disruptive and lead to protein misfolding and aggregation. To test this hypothesis, we analyzed the relationship between codon usage bias and protein structure in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse. Using both the Mantel-Haenszel procedure, which applies to categorical data, and a newly developed association test for continuous variables, we find that translationally optimal codons associate with buried residues and also with residues at sites where mutations lead to large changes in free energy (DeltaDeltaG). In each species, only a subset of all amino acids show this signal, but most amino acids show the signal in at least one species. By repeating the analysis on a reduced data set that excludes interdomain linkers, we show that our results are not caused by an association of rare codons with solvent-accessible linker regions. Finally, we find that our results depend weakly on expression level; the association between optimal codons and buried sites exists at all expression levels, but increases in strength as expression level increases.
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.