title: Evolutionary conservation of codon optimality reveals hidden signatures of cotranslational folding.
abstract: The choice of codons can influence local translation kinetics during protein synthesis. Whether codon preference is linked to cotranslational regulation of polypeptide folding remains unclear. Here, we derive a revised translational efficiency scale that incorporates the competition between tRNA supply and demand. Applying this scale to ten closely related yeast species, we uncover the evolutionary conservation of codon optimality in eukaryotes. This analysis reveals universal patterns of conserved optimal and nonoptimal codons, often in clusters, which associate with the secondary structure of the translated polypeptides independent of the levels of expression. Our analysis suggests an evolved function for codon optimality in regulating the rhythm of elongation to facilitate cotranslational polypeptide folding, beyond its previously proposed role of adapting to the cost of expression. These findings establish how mRNA sequences are generally under selection to optimize the cotranslational folding of corresponding polypeptides.
authors.affiliation: Department of Biology, Stanford University, Stanford, California, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pechmann
authors.forename: Judith
authors.initials: J
authors.lastname: Frydman
mesh_terms: D000595:Amino Acid Sequence; D003062:Codon / Q000235:genetics*; D019143:Evolution, Molecular; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018994:Myosin Light Chains / Q000737:chemistry; D014176:Protein Biosynthesis / Q000235:genetics*; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000235:genetics*; D012343:RNA, Transfer / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics; D013045:Species Specificity; D015003:Yeasts
chemical_list: D003062:Codon; C113979:MLC1 protein, S cerevisiae; D018994:Myosin Light Chains; D029701:Saccharomyces cerevisiae Proteins; D012343:RNA, Transfer