Stochastic variation in the concentration of a repressor activates GAL genetic switch:: implications in evolution of regulatory network

In Saccharomyces cerevisiae, a recessive mutation in the signal transducer encoded by GAL3 leads to a significant lag in the induction of GAL genes, referred to as long term adaptation phenotype (LTA). Further, gal3 mutation in combination with other genetic defects leads to the non-inducibility of GAL genes. It was shown that the expression of GAL1 encoded galactokinase, a redundant GAL3 like signal transducer, eventually substitutes for the lack of GAL3 signal transduction function. However, how GAL1 gets induced in the absence of GAL3 is not clear. We hypothesize that GAL1 induction in gaB cells exposed to galactose is due to a stochastic decrease in the repressor, Gal80p concentration, leading to heterogeneity in the population. This observation explains not only LTA observed in gaB cells but also explains the non-inducibility of gaB mutants in combination with other genetic defects. By recruiting a dedicated signal transducer, GAL3, S. cerevisiae GAL switch has evolved to overcome the fortuitous induction, which occurs due to low signal to noise ratio in certain mutants of Escherichia coli and Kluveromyces lactis. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.