Stochastic galactokinase expression underlies GAL gene induction in a GAL3 mutant of Saccharomyces cerevisiae.

GAL1 and GAL3 are paralogous signal transducers that functionally inactivate Gal80p to activate the Gal4p-dependent transcriptional activation of GAL genes in Saccharomyces cerevisiae in response to galactose. Unlike a wild-type strain, the gal3∆ strain shows delayed growth kinetics as a result of the signaling function of GAL1. The mechanism ensuring that GAL1 is eventually expressed to turn on the GAL switch in the gal3∆ strain remains a paradox. Using galactose and histidine growth complementation assays, we demonstrate that 0.3% of the gal3∆ cell population responds to galactose. This is corroborated by flow cytometry and microscopic analysis. The galactose responders and nonresponders isolated from the galactose-adapted population attain the original bimodal state and this phenotype is found to be as hard wired as a genetic trait. Computational analysis suggests that the log-normal distribution in GAL4 synthesis can lead to bimodal expression of GAL80, resulting in the bimodal expression of GAL genes. Heterozygosity at the GAL80 but not at the GAL1, GAL2 or GAL4 locus alters the extent of bimodality of the gal3∆ cell population. We suggest that the asymmetric expression pattern between GAL1 and GAL3 results in the ability of S. cerevisiae to activate the GAL pathway by conferring nongenetic heterogeneity.