ArticleGenome biology2010
The rate of the molecular clock and the cost of gratuitous protein synthesis.
Article in Genome biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- GroEL/ES chaperonin unfolds then encapsulates a nascent protein on the ribosome.Nature communications · 2025Article
- Functional Optimization in Distinct Tissues and Conditions Constrains the Rate of Protein Evolution.Molecular biology and evolution · 2024Article
- Highly Abundant Proteins Are Highly Thermostable.Genome biology and evolution · 2023Article
- Purifying selection enduringly acts on the sequence evolution of highly expressed proteins in Escherichia coli.G3 (Bethesda, Md.) · 2022Article
- DnaK response to expression of protein mutants is dependent on translation rate and stability.Communications biology · 2022Article
- Avoidance of protein unfolding constrains protein stability in long-term evolution.Biophysical journal · 2021Article
- Universal Constraints on Protein Evolution in the Long-Term Evolution Experiment with Escherichia coli.Genome biology and evolution · 2021Article
- The Relationship between the Misfolding Avoidance Hypothesis and Protein Evolutionary Rates in the Light of Empirical Evidence.Genome biology and evolution · 2021Article
- Abundance Imparts Evolutionary Constraints of Similar Magnitude on the Buried, Surface, and Disordered Regions of Proteins.Frontiers in molecular biosciences · 2021Article
- Protein Melting Temperature Cannot Fully Assess Whether Protein Folding Free Energy Underlies the Universal Abundance-Evolutionary Rate Correlation Seen in Proteins.Molecular biology and evolution · 2019Article
- The fitness cost and benefit of phase-separated protein deposits.Molecular systems biology · 2019Article
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- Entrainment to periodic initiation and transition rates in a computational model for gene translation.PloS one · 2014Article
- A model of proteostatic energy cost and its use in analysis of proteome trends and sequence evolution.PloS one · 2014Article
- Evaluating the fitness cost of protein expression in Saccharomyces cerevisiae.Genome biology and evolution · 2013Article
- Protein misinteraction avoidance causes highly expressed proteins to evolve slowly.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Large-scale experimental studies show unexpected amino acid effects on protein expression and solubility in vivo in E. coli.Microbial informatics and experimentation · 2011Article
- Misfolded proteins impose a dosage-dependent fitness cost and trigger a cytosolic unfolded protein response in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Community transcriptomics reveals universal patterns of protein sequence conservation in natural microbial communities.Genome biology · 2011Article
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3 authors.
Funding
Abstract
backgroundThe nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, is among the central questions of molecular evolution. Protein expression level is the dominant determinant of the clock rate in a number of organisms. It has been suggested that highly expressed proteins evolve slowly in all species mainly to maintain robustness to translation errors that generate toxic misfolded proteins. Here we investigate this hypothesis experimentally by comparing the growth rate of Escherichia coli expressing wild type and misfolding-prone variants of the LacZ protein.
resultsWe show that the cost of toxic protein misfolding is small compared to other costs associated with protein synthesis. Complementary computational analyses demonstrate that there is also a relatively weaker, but statistically significant, selection for increasing solubility and polarity in highly expressed E. coli proteins.
conclusionsAlthough we cannot rule out the possibility that selection against misfolding toxicity significantly affects the protein clock in species other than E. coli, our results suggest that it is unlikely to be the dominant and universal factor determining the clock rate in all organisms. We find that in this bacterium other costs associated with protein synthesis are likely to play an important role. Interestingly, our experiments also suggest significant costs associated with volume effects, such as jamming of the cellular environment with unnecessary proteins.
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