Ribosomal mutations affecting the translation of genes that use non-optimal codons

FEBS J. 2014 Aug;281(16):3701-18. doi: 10.1111/febs.12892. Epub 2014 Aug 8.


Genes that are laterally acquired by a new host species often contain codons that are non-optimal to the tRNA repertoire of the new host, which may lead to insufficient translational levels. Inefficient translation can be overcome by different mechanisms, such as incremental amelioration of the coding sequence, compensatory mutations in the regulatory sequences leading to increased transcription or increase in gene copy number. However, there is also a possibility that ribosomal mutations can improve the expression of such genes. To test this hypothesis, we examined the effects of point mutations in the endogenous ribosomal proteins S12 and S5 in Escherichia coli, which are known to be involved in the decoding of the mRNA, on the efficiency of translation of exogenous genes that use non-optimal codons, in vivo. We show that an S12 mutant in E. coli is able to express exogenous genes, with non-optimal codons, to higher levels than the wild-type, and explore the mechanisms underlying this phenomenon in this mutant. Our results suggest that the transient emergence of mutants that allow efficient expression of exogenous genes with non-optimal codons could also increase the chances of fixation of laterally transferred genes.

Keywords: codon usage; horizontal gene transfer; ribosomal protein S12; ribosome; rpsL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AT Rich Sequence
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Codon*
  • Drug Resistance, Bacterial
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Mutation, Missense
  • Protein Biosynthesis*
  • RNA, Bacterial / genetics
  • RNA, Bacterial / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / metabolism
  • Ribosomes / physiology*


  • Codon
  • Escherichia coli Proteins
  • RNA, Bacterial
  • RNA, Messenger
  • Ribosomal Proteins
  • RpsL protein, E coli
  • Chloramphenicol O-Acetyltransferase