Rare codon effect

Some authors have been concerned that the use of codons for which there is a low level oftRNA in E. coli might limit expression. This rare codon effect has only been observed in extreme cases where a protein is massively overproduced and contains several rare Arg-codons (e.g. Ref. 99). This completely depletes the concentration of charged tRNA in the cell. Since an effect will only be seen if translation undergoes chain termination at the slowing point, it would not be expected to play any role where only a few hundred molecules are being synthesized per cell, as in phage display. 

Kane, J. E. (1995). Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr. Opin. Biotechnol. 6,494-500. 

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