ArticleProceedings of the National Academy of Sciences of the United States of America2012
Protein misinteraction avoidance causes highly expressed proteins to evolve slowly.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed.
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- In silico prediction of variant effects: promises and limitations for precision plant breeding.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2025Review
- Cell Compartment is a Predictor of Protein Rate of Evolution, but not in the Manner Expected: Evidence Against the Extended Complexity Hypothesis.Genome biology and evolution · 2025Article
- High Gene Expression Predicts Extremely Low Segregation of Deleterious Mutations in Large Penguin Populations.Molecular biology and evolution · 2025Article
- Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution.Molecular neurobiology · 2025Article
- Correlations of gene expression, codon usage bias, and evolutionary rates of the mitochondrial genome show tissue differentiation in Ophioglossum vulgatum.BMC plant biology · 2025Article
- Genome-wide impact of codon usage bias on translation optimization in Drosophila melanogaster.Nature communications · 2024Article
- Comparative Genomic Analysis of the Pattern of Evolution of Male and Female Reproductive Proteins in Seed Beetles.Genome biology and evolution · 2024Article
- Classical cadherins evolutionary constraints in primates is associated with their expression in the central nervous system.PloS one · 2024Article
- Transcriptome analysis ofFrontiers in plant science · 2024Article
- Purifying selection drives distinctive arsenic metabolism pathways in prokaryotic and eukaryotic microbes.ISME communications · 2024Article
- Agglomeration: when folded proteins clump together.Biophysical reviews · 2023Review
- Highly Abundant Proteins Are Highly Thermostable.Genome biology and evolution · 2023Article
- Genes Vary Greatly in Their Propensity for Collateral Fitness Effects of Mutations.Molecular biology and evolution · 2023Article
- What Has Genomics Taught An Evolutionary Biologist?Genomics, proteomics & bioinformatics · 2023Review
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57 more citing papers are in PubMed but not listed here.
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4 authors.
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Abstract
The tempo and mode of protein evolution have been central questions in biology. Genomic data have shown a strong influence of the expression level of a protein on its rate of sequence evolution (E-R anticorrelation), which is currently explained by the protein misfolding avoidance hypothesis. Here, we show that this hypothesis does not fully explain the E-R anticorrelation, especially for protein surface residues. We propose that natural selection against protein-protein misinteraction, which wastes functional molecules and is potentially toxic, constrains the evolution of surface residues. Because highly expressed proteins are under stronger pressures to avoid misinteraction, surface residues are expected to show an E-R anticorrelation. Our molecular-level evolutionary simulation and yeast genomic analysis confirm multiple predictions of the hypothesis. These findings show a pluralistic origin of the E-R anticorrelation and reveal the role of protein misinteraction, an inherent property of complex cellular systems, in constraining protein evolution.
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