Causes and Effects of N-Terminal Codon Bias in Bacterial Genes

TLDR

The genetic code is redundant, yet synonymous codon changes can substantially affect protein expression, largely through alterations in 5′ mRNA structure. A synthetic library of 14,000 N‑terminal variants from 137 E. coli genes revealed that rare codons unexpectedly increased protein expression more than common codons, with downstream RNA structure at initiation sites being the major determinant.

Abstract

Exploiting Redundancy The genetic code is redundant—multiple codons can code for the same amino acid. So-called synonymous codon changes within genes can nonetheless have substantial affects on protein expression, which have been attributed to changes in the structure of 5′ messenger RNAs, among other factors. Goodman et al. (p. 475 , published online 26 September) built and measured the expression of a synthetic library of 14,000 variant N-terminal sequences of 137 Escherichia coli genes to show that, unexpectedly, rare codons had a bigger effect on increasing protein expression than more common codons. Increased RNA structure downstream of translation initiation appeared to represent the major determinant of expression differences owing to codon usage.