Slow Growth and Increased Spontaneous Mutation Frequency in Respiratory Deficient afo1^- Yeast Suppressed by a Dominant Mutation in ATP3

A yeast deletion mutation in the nuclear-encoded gene, , which codes for a mitochondrial ribosomal protein, led to slow growth on glucose, the inability to grow on glycerol or ethanol, and loss of mitochondrial DNA and respiration. We noticed that (-) yeast readily obtains secondary mutations that suppress aspects of this phenotype, including its growth defect. We characterized and identified a dominant missense suppressor mutation in the gene. Comparing isogenic slowly growing rho-zero and rapidly growing suppressed (-) strains under carefully controlled fermentation conditions showed that energy charge was not significantly different between strains and was not causal for the observed growth properties. Surprisingly, in a wild-type background, the dominant suppressor allele of still allowed respiratory growth but increased the petite frequency. Similarly, a slow-growing respiratory deficient afo1(-) strain displayed an about twofold increase in spontaneous frequency of point mutations (comparable to the rho-zero strain) while the suppressed strain showed mutation frequency comparable to the respiratory-competent WT strain. We conclude, that phenotypes that result from afo1(-) are mostly explained by rapidly emerging mutations that compensate for the slow growth that typically follows respiratory deficiency.