LB 17-182 - A metabolic understanding of adaptation to metals in yeast

Background/Question/Methods:

When yeasts are growing in high metal concentrations, they can maintain their homeostasis by either reducing the metal cytoplasmic concentration or by neutralizing the side-effects of the metal on metabolism and other cell functions. These adaptations require energy, both for their development (e.g., synthesizing pumps) and their maintenance (e.g., pumping out the metal). Because cells also need energy to grow, energy can provide a framework to evaluate the effects of different adaptations on growth rate. This theory makes specific predictions about the shape of tolerance curves (i.e., growth rates under different metal concentrations) and how they change with nutrient addition. It also predicts that one way that a cell can deal with the metal is to eat more food or spend less energy on less important tasks.

Results/Conclusions:

In this study, we apply this framework to copper-tolerant yeasts studied by Gerstein et al. (2015) to understand the metabolic impacts of mutations that arose in this short-term adaptation experiment. We tested the metabolic framework by comparing quantitative predictions about tolerance curves. Furthermore, we test predictions about the pleiotropic effects of mutations on the performance of yeasts in different metals. For example, mutations that help cell obtain more energy are expected to increase the fitness of yeasts in almost all metals, but a mutation with an effect specific to a single metal would only incur extra costs in other metals. This framework also allows predictions about the simultaneous effect of multiple metals on growth dynamics. We provide evidence in support of the importance of considering cell energy budget as a framework for understanding adaptation to toxins, like metals, and their pleiotropic effects.