Progressive decrease in protein synthesis accuracy induced by streptomycin in Escherichia coli

Abstract

THE passage of genetic information from gene to polypeptide does not proceed with perfect fidelity^1–3, but it is not known what short and long-term cellular responses may be induced by decreases in the accuracy of protein synthesis. Errors in gene expression may tend to increase their own rate of production⁴, and thus could constitute a limiting instability of cellular life. The synthesis of inaccurate RNA, RNA polymerases, tRNAs, tRNA modifying enzymes, tRNA charging enzymes and ribosomal proteins are potential pathways for the perpetuation or amplification of errors. Such errors may be inducible in vivo by external chemical agents and may constitute an indirect pathway for mutagenesis^5–8. An enhanced rate of such errors may be the mechanism by which certain deleterious mutations exert their effects. Here we report the results of experiments with Escherichia coli designed to detect evidence of self amplification of errors in protein synthesis. If such error feedback is quantitatively significant, a slight increase in the pre-existing error rate should be followed by a progressive decrease in the accuracy of protein synthesis. While this process could lead to a new stable level and thus need not precipitate a catastrophic breakdown, some late effects should be observable if the mechanisms are at all as hypothesised.