RT Journal Article SR Electronic T1 Population diversification in a yeast metabolic program promotes anticipation of environmental shifts JF bioRxiv FD Cold Spring Harbor Laboratory SP 002907 DO 10.1101/002907 A1 Ophelia S. Venturelli A1 Ignacio Zuleta A1 Richard M. Murray A1 Hana El-Samad YR 2014 UL http://biorxiv.org/content/early/2014/02/21/002907.abstract AB Delineating the strategies by which cells contend with combinatorial changing environments is crucial for understanding cellular regulatory organization. When presented with two carbon sources, microorganisms first consume the carbon substrate that supports the highest growth rate (e.g. glucose) and then switch to the secondary carbon source (e.g. galactose), a paradigm known as the Monod model. Sequential sugar utilization has been attributed to transcriptional repression of the secondary metabolic pathway, followed by activation of this pathway upon depletion of the preferred carbon source. In this work, we challenge this notion. Although Saccharomyces cerevisiae cells consume glucose before galactose, we demonstrate that the galactose regulatory pathway is activated in a fraction of the cell population hours before glucose is fully consumed. This early activation reduces the time required for the population to transition between the two metabolic programs and provides a fitness advantage that might be crucial in competitive environments. Importantly, these findings define a new paradigm for the response of microbial populations to combinatorial carbon sources.