The combined influence of codon composition and tRNA copy number regulates translational efficiency by influencing synonymous nucleotide substitution

Codon usage bias is an important genomic phenomenon, where highly expressed genes use optimal codons for smoother translation with high yield, facilitated by the cognate tRNAs. Here, we presented the tRNA co-adaptation index (co-AI) by correlating tRNA gene copy number and codon composition in Saccharomyces cerevisiae. We observed that this co-AI is positively correlated with protein abundance and translation rate. Considering nucleotide substitutions, co-AI influences synonymous substitutions more than gene expression and protein abundance, the most important determinants of evolutionary rate. Co-AI correlates positively with mRNA secondary structure stability and mRNA half-life, which may lead to protein accumulation under high co-AI. However, the highly expressed proteins encoded by high co-AI genes are assisted by molecular chaperones to attain their proper functional conformation and prevent accumulation.