Preferential use of minor codons in the translation initiation region of human genes.

More than 31,000 protein-coding sequences (CCDS) have been identified in the human genome. Here, we analyzed codon usage in all human CCDS and found that there is a preferential usage of minor codons for Ala (CGC), Pro (CCG), Ser (UCG), and Thr (ACG) in the initial 50-codon sequences of the CCDS. These codons, with consensus XCG sequences, are most infrequently used among their synonymous codons. Thus, the tRNA concentrations per codon are considered to be highest for the minor codons for Ala, Pro, Ser and Thr in comparison with other synonymous codons for each of them to enhance the translation efficiency. This suggests that human genes are regulated at the level of translation by preferentially using minor codons within the first 50 codons of the CCDS. This hypothesis was experimentally confirmed by comparing the expression of the luciferase gene encoded by minor codons with that encoded by major codons.