ArticleCell2008
Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.
Article in Cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 666 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
666 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,106 citations in OpenAlex.
- Synonymous but Not Silent: The Codon Usage Code for Gene Expression and Protein Folding.Annual review of biochemistry · 2021Pooled it
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- Translation accuracy in E. coli.Nucleic acids research · 2026Article
- Why structural divergence varies among residues in enzyme evolution: contributions of mutation, stability, and activity constraints.Molecular biology and evolution · 2026Article
- Molecular evolution in light of regulatory-coding epistasis.EMBO reports · 2026Review
- Evolution of a core ribosomal innovation in octopus.bioRxiv : the preprint server for biology · 2026Article
- The importance of nonsense errors: Estimating the rates and implications of ribosome drop-off during protein synthesis.PLoS genetics · 2026Article
- Inter-individual gene expression variability implies stable regulation of brain-biased genes across organs in three ray-finned fishes.bioRxiv : the preprint server for biology · 2026Article
- Multiple molecular and cellular properties jointly affect protein and site-specific evolutionary rates.bioRxiv : the preprint server for biology · 2026Article
- Prediction and functional interpretation of inter-chromosomal genome architecture from DNA sequence with TwinC.Nature communications · 2026Article
- The pangenome ofiScience · 2026Article
- Hierarchical evolution of the proteobacterial essential chaperone SecB reveals non-neutral synonymous evolution under extreme purifying selection.Molecular genetics and genomics : MGG · 2026Article
- Mistranslation suppresses mistranscription in eukaryotes.Nature communications · 2026Article
- Membrane-embedded polar residues target membrane proteins for degradation by the quality control protease FtsH.Nature communications · 2026Article
606 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
2 authors at 2 institutions in 1 country.
Funding
Abstract
Strikingly consistent correlations between rates of coding-sequence evolution and gene expression levels are apparent across taxa, but the biological causes behind the selective pressures on coding-sequence evolution remain controversial. Here, we demonstrate conserved patterns of simple covariation between sequence evolution, codon usage, and mRNA level in E. coli, yeast, worm, fly, mouse, and human that suggest that all observed trends stem largely from a unified underlying selective pressure. In metazoans, these trends are strongest in tissues composed of neurons, whose structure and lifetime confer extreme sensitivity to protein misfolding. We propose, and demonstrate using a molecular-level evolutionary simulation, that selection against toxicity of misfolded proteins generated by ribosome errors suffices to create all of the observed covariation. The mechanistic model of molecular evolution that emerges yields testable biochemical predictions, calls into question the use of nonsynonymous-to-synonymous substitution ratios (Ka/Ks) to detect functional selection, and suggests how mistranslation may contribute to neurodegenerative disease.
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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.