Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution

By Wilke Drummond, D. A. Drummond, Claus O. Wilke. Cell, 2008

1,057 citations recorded by the source corpus.

Summary The biological causes of selective pressures on coding-sequence evolution remain controversial, despite the surprising consistency of covariation between common measures of evolutionary change (substitution rates) and gene expression (mRNA levels, codon usage) across taxa. We carry out a unified analysis which reveals these conserved patterns in E. coli, yeast, worm, fly, mouse, and human, and suggests that all 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 the observed covariation. The mechanistic model of molecular evolution which emerges yields testable biochemical predictions, calls into question use of nonsynonymous-to-synonymous substitution ratios (Ka/Ks) to detect functional selection, and suggests how mistranslation may contribute to neurodegenerative disease.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/52e1bc05e60444f2bb6fb0572fe203459f9ccd44

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Citations in the corpus

Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition (2016, neutral): “1982; Akashi, 1994; Akashi & Gojobori, 2002; Drummond & Wilke, 2008; Kudla et al, 2009; Novoa & Ribas de Pouplana, 2012).”
Codon Bias as a Means to Fine-Tune Gene Expression (2015, background): “, catalytic residues) may also be encoded by frequent codons not because of folding kinetics but because these frequent codons may enhance translational accuracy of these important amino acids (Drummond and Wilke, 2008).”
A Universal Trend of Reduced mRNA Stability near the Translation-Initiation Site in Prokaryotes and Eukaryotes (2010, background): “particular in fast-growing microbes [2,3,8,11], these two correlations likely reflect the same underlying effect.”
The evolutionary origin of orphan genes (2011, background): “One factor that could explain many of these general trends is the cost associated with translation errors and protein misfoldin”
Pathways of cellular proteostasis in aging and disease (2018, background): “Production of misfolded proteins is further increased by stochastic errors of protein biogenesis occurring at the level of transcription and mRNA maturation and translation (Sachidanandam et al., 2001; Ng and Henikoff, 2006; Drummond and Wilke, 2008).”
Cellular strategies for controlling protein aggregation (2010, background): “These include translational errors, leading to the misincorporation of amino acids, and assembly defects of protein complexes, leading to the accumulation of non-complexed protein species that are frequently prone to aggregatio”
The N‐end rule pathway and regulation by proteolysis (2011, background): “Errors in specific steps of protein synthesis result, conservatively, in 5–20% of molecules of a 50 kDa protein containing at least one missense alteration that is not encoded by DNA.(307,308) Premature termination of translation and frameshifts are additional sources of defective polypeptides.”
Stability effects of mutations and protein evolvability. (2009, background): “Another key factor arises from errors occurring during protein synthesis (phenotypic mutations) [46,47 ,48 ].”
Inferring Stabilizing Mutations from Protein Phylogenies: Application to Influenza Hemagglutinin (2009, background): “Mutations can also have other deleterious effects, such as altering mRNA stability [50], codon usage [51], or the accuracy and efficiency of translation [43,51,52].”
Codon optimality is a major determinant of mRNA stability (2015, background): “Critically, optimal codons are postulated to be decoded faster and more accurately by the ribosome than non-optimal codons (Akashi, 1994; Drummond and Wilke, 2008), which are hypothesized to slow translation elongation (Novoa and Ribas de Pouplana, 2012; Tuller et al., 2010).”
PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life (2012, background): “…largely by its function— has a surprisingly large impact on its evolutionary trajectory, controlling the extent of purifying selection on its amino acid sequence (22), its codon usage (23), translation regime (24), folding accuracy (25, 26), and its genomic organization (27, 28), among others.”
Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites (2014, background): “…(Bershtein et al. 2006, Gong et al. 2013), lethal mutagenesis (Chen & Shakhnovich 2009), determinants of evolutionary rate at protein level (Drummond & Wilke 2008, Serohijos et al. 2012), the evolution of novel function (Bloom et al. 2006, Tokuriki et al. 2008), and the expected…”
Selection for Protein Stability Enriches for Epistatic Interactions (2018, background): “However, this extremely small stability margin is a well-known artifact of our decision 250 to model fitness as a step function in stability [8] rather than a more realistic logistic function [11,30], 251 and the fact that our simulations do not include any of the other factors that would tend to in”