Alterations in mitochondrial DNA of yeast which accompany genetically and environmentally controlled changes in rho- mutability.

Alterations in the physical characteristics of mitochondrial DNA accompanied increased spontaneous mutability to cytoplasmic respiratory-deficiency in yeast. Two systems were used to modify mutation rates, one physiological, the other genetic. Cells in log phase were shown to be more mutable than cells in stationary phase, and glucose-repressed cells were shown to be more mutable than unrepressed cells. A nuclear gene which acts as a mitochondrial mutator was found to increase spontaneous mutation rate by a factor of ten. An increase in endogenous formation of G+G-rich fragments of mt-DNA accompanied a physiological state conducive to higher mutability, and it is proposed that increased in vivo digestion of A+T-rich regions is involved in these alterations. Greater nuclease(s) activity accompanied the presence of the mutator gene, and it is proposed that this gene is concerned with the regulation of nuclease activity or with repair mechanisms.