Use of physiological constraints to identify quantitative design principles for gene expression in yeast adaptation to heat shock

We used mathematical models and analysis of in silico gene expression profiles (GEPs) to understand how changes in gene expression correlate to an efficient response of yeast cells to heat shock. An exhaustive set of GEPs, matched with the corresponding set of enzyme activities, was simulated and analyzed. The effectiveness of each profile in the response to heat shock was evaluated according to relevant physiological and functional criteria. The small subset of GEPs that lead to effective physiological responses after heat shock was identified as the result of the tuning of several evolutionary criteria. The experimentally observed transcriptional changes in response to heat shock belong to this set and can be explained by quantitative design principles at the physiological level that ultimately constrain changes in gene expression.Our theoretical approach suggests a method for understanding the combined effect of changes in the expression of multiple genes on the activity of metabolic pathways, and consequently on the adaptation of cellular metabolism to heat shock. This method identifies quantitative design principles that facilitate understating the response of the cell to stress.Cells mount adaptive responses that involve changes in gene expression in order to survive environmental stress. These changes lead to shifts in the activity of the corresponding proteins and often to observable phenotypes. In each stress condition, the effectiveness of the cellular responses is subordinated to a variety of functional constraints. Ultimately, any change in gene expression and protein activity must allow the cell to survive the stress and to maintain a metabolism that allows reproduction (or at least survival until stress no longer exists and normal reproduction can occur). Out of the wealth of physically possible gene expression changes, only a small set of patterns allows the cell to effectively survive a given type of stress. For instance, a complex and well-defined p