Low-usage codons and rare codons of Escherichia coli Mini Review

In Escherichia coli (E. coli), a low-usage codon is defined as a codon that is used rarely or infrequently in the genome with usage frequency lower than the smallest value (or frequency cut-off) among the usage frequencies of non-degenerate codons (Met codon AUG and Trp codon UGG) and the optimal codons for amino acids Leu, Ile, Val, Ser, Pro, Thr, Ala, Arg, Gly and Gln that have 2 or more degenerate codons with each having specific corresponding cognate tRNA for the optimal codon. A rare codon (RC), an infrequent codon or a minor codon is equivalently defined as a synonymous codon or a stop codon that is not only used rarely or infrequently in a genome but also decoded by a low-abundant tRNA (rare tRNA) or other factor(s) in an organism. The translational rate for a sense RC is much lower than that for a common (major) codon due to tRNA availability. A low-usage codon is not necessarily a RC, e.g., Cys codons UGU and UGC, Thr codons ACU and ACG, or His codons CAC and CAU are not rare codons of E. coli . However, a RC is definitely a low-usage codon. In E. coli, there are about 30 low-usage synonymous sense codons but only 20 of them are determined to be the bacterial RCs including 7 (AGG, AGA, CGA, CUA, AUA, CCC and CGG) used at a frequency of < 0.5% (Group I) and 13 (ACA, CCU, UCA, GGA, AGU, UCG, CCA, UCC, GGG, CUC, CUU, UCU and UUA) used at a frequency of > 0.5% (Group II). Studies have demonstrated that all the RCs in Group I and the first 6 RCs in Group 2 can cause translational problems in E. coli.