Saccharomyces cerevisiae Raw sequence reads. Saccharomyces cerevisiae

As an ancient winning strategy of microorganisms, glucose repression mechanism has become specialized to perfection in Saccharomyces cerevisiae. The galactose (GAL) metabolism network is stringently regulated by glucose repression in yeast and has been a classic system for studying gene regulation. We show here that the population of S. cerevisiae living in fermented milks has autonomously reinstated an ancient version of the structural GAL genes through introgression. The introgressed GAL network has completely abolished the glucose repression and conversed from a strictly inducible to a constitutive system through coordinative polygenic changes in the regulatory components of the network, including transitions in the upstream repressing sequence site of GAL4 that impair Mig1p-mediated repression and loss of function of the inducer Gal3p and the repressor Gal80p. In addition, the introgressed GAL2 gene has been duplicated while the native HXT6 and HXT7 genes have been inactivated, resulting in galactose-over-glucose preference and elevated galactose utilization rate. Relying on the reverse evolution of the GAL network, the non-lactose fermenting yeast has become a dominant species co-existing with other lactose fermenting microorganisms in fermented milks. Our results also provide new clues for developing yeast strains devoid of barriers to co-utilization of different sugars.