Population-level heterogeneity as a reflection of mixed strategy: A computational perspective on the Crabtree effect

Is population-level heterogeneity a reflection of distinct subpopulations, exhibiting different metabolic functions, or dynamic metabolism of individuals within the population? This fascinating question has remained a subject of great interest in studying metabolic specialization in microorganisms. The Crabtree effect - i.e., the ability of some microorganisms to switch from respiration to fermentation in the presence of oxygen - is an appropriate case study to address the aforementioned question. Game-theoretical approaches have been routinely used to examine and explain the way a microorganism, such as yeast, would switch between the two ATP-producing pathways, i.e., respiration and fermentation. Here we attempt to explain the switch between respiration and fermentation in yeast by constructing a simple metabolic switch. We then utilize an individual-based model, in which each individual is equipped with all the relevant chemical reactions, to see how cells equipped with such metabolic switch would behave in different conditions. We further investigate our proposed metabolic switch using the game-theoretical approach. Based on this model, we postulate that the population-level metabolic heterogeneity in microorganisms can simply arise from individuals utilizing a mixed strategy.