Some mutations in gene coding regions exchange one synonymous codon for another, and thus do not alter the amino acid sequence of the encoded protein. Even though they are often called 'silent,' these mutations may exhibit a plethora of effects on the living cell. Therefore, they are often selected during evolution, causing synonymous codon usage biases in genomes. Comparative analyses of bacterial, archaeal, fungal, and human cancer genomes have found many links between a gene's biological role and the accrual of synonymous mutations during evolution. In particular, highly expressed genes in certain functional categories are enriched with optimal codons, which are decoded by the abundant tRNAs, thus enhancing the speed and accuracy of the translating ribosome. The set of genes exhibiting codon adaptation differs between genomes, and these differences show robust associations to organismal phenotypes. In addition to selection for translation efficiency, other distinct codon bias patterns have been found in: amino acid starvation genes, cyclically expressed genes, tissue-specific genes in animals and plants, oxidative stress response genes, cellular differentiation genes, and oncogenes. In addition, genomes of organisms harboring tRNA modifications exhibit particular codon preferences. The evolutionary trace of codon bias patterns across orthologous genes may be examined to learn about a gene's relevance to various phenotypes, or, more generally, its function in the cell.

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and ‘Centro de Excelencia Severo Ochoa 2013-2017′ SEV-2012-0208), a European Research Council Consolidator grant IR-DC (616434), Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), the EMBO Young Investigator Program, the EMBL-CRG Systems Biology Program, the AXA research fund, the FP7 project 4DCellFate (277899), the FP7 project MAESTRA (ICT-2013-612944), the FP7 REGPOT grant InnoMol, the Croatian Science Foundation Grant HRZZ-9623, and the Croatian Ministry of Science and Sport Grant 098-0000000-3168