Streptomycin and Misreading of the Genetic Code

Abstract

Historical Background
In 1961 we accidentally isolated a streptomycin-resistant auxotroph whose arginine requirement could be satisfied by streptomycin (Gorini, Gundersen and Burger 1961). It was shown a few years later (Gorini and Kataja 1964a), using the same streptomycin-resistant parent and by selecting for streptomycin dependence in minimal medium but not in broth, that a class of mutants defective in a number of unrelated metabolic pathways could be easily obtained. The members of this class share the property of “conditional streptomycin dependence (CSD).” It could be shown in extracts that the enzyme normally missing in the mutant was formed during growth in the presence of streptomycin. We suggested that streptomycin might induce mistakes in the transmission of information from DNA to protein, compensating for the effect of the mistake encoded in the mutant DNA. Such a mechanism is analogous to that of “informational suppression” (Gorini 1970), by which the effect of a mutation persists at the level of the gene but is suppressed at the level of translation. However, informational suppression is found to be the consequence of a mutation in one of the molecules involved in the translation process (most commonly in a tRNA), whereas suppression in the case of CSD mutants appeared to depend on the environment, i.e., the presence or absence of streptomycin in the growth medium. We have suggested the designation of “phenotypic suppression” for this streptomycin effect.

If streptomycin produces phenotypic suppression by inducing mistakes in translation, then the drug could be expected to induce mistakes...