Effects of different types of codon choice. (A) Genes encoded primarily with optimal codons (blue) are rapidly and efficiently translated. (B) Genes encoded primarily with suboptimal or slowly decoded codons (orange) are inefficiently translated; their mRNAs exhibit decreased stability, mediated in yeast by Dhh1 protein. (C) Inhibitory codon pairs (red box) are very slowly decoded, reduce protein output significantly, and sometimes recruit quality control machinery. (D) The efficiency of translation initiation influences the magnitude of the effects of suboptimal codon use on expression (ratio of expression of synonymous variants encoding the same protein). (E) A change in the amount of two specific tRNAs drives cancer metastasis and modulates expression of specific genes. (F) Harmonized codon use, a combination of rapidly and slowly decoded codons, can facilitate co-translational protein folding to obtain biologically active molecules.