Proliferation specific codon usage facilitates oncogene translation

Summary Tumors evolve under selection for gene mutations that give a growth advantage to the cancer cell. Intriguingly, some cancer genes are more often found mutated in tumors than their closely related family members. For example, KRAS mutations are more frequently observed in cancer in comparison to HRAS and NRAS. Here, we find that for RAS and six oncogene families, the most prevalent mutated members in cancer have a codon usage characteristic of genes involved in proliferation. The codon usage of KRAS is more adapted to be efficiently translated in proliferative cells than the codon usage of HRAS. We also show that the translation efficiency of KRAS varies between cell lines in a manner related to their tRNA expression. Altogether, our study demonstrates that a dynamic translation program contributes to shaping the expression profiles of oncogenes. We propose that codon bias related to cell proliferation contributes to the prevalence of mutations in certain members of oncogene families.