On the dependence of spontaneous mutation rates on the functional state of genes

Spontaneous mutation of some genes was studied in haploid adenine and leucine auxotrophic yeast Saccharomyces. It was shown that a decrease in the amount of adenine (from 500 to 0 mg l-1) or leucine (from 300 to 0.3 mg l-1) in the medium, simultaneously with the transition from repression to derepression of the biosynthesis of these metabolites, resulted in a 15- to 150-fold increase in the reversion rate of genes ade 2 and leu2, respectively, for different strains. At the same time the mutation rate of suppressor genes varied relatively little (up to five-fold), and that of gene lys did not change at all. It was also demonstrated (on gene leu2) that the mutation rate is determined by the composition of the nutrient medium at the time of the S-phase of the cell cycle and it does not depend on the cultivation conditions during the presynthetic period. We discuss the hypothesis that derepressed genes mutate with a significantly higher rate than genes in the repressed state.