Fig. 1

General scheme for the proposed genome-driven evolutionary game theory approach. Annotated genomes of community members are used to construct genome-scale metabolic models. For each possible pair of genotypes in the community, constraint-based analysis tools for metabolic models, such as flux balance analysis⁵¹, are used to estimate the fitness (or “payoff”) of each genotype as they engage in a specific metabolite-mediated interaction. These payoffs form the payoff matrix of the game. Based on this payoff matrix, we identify all pure strategy Nash equilibria of the game, using an automated pipeline (NashEq Finder, see “Methods”). The payoff matrix also allows one to model evolutionary dynamics (i.e., how genotype frequencies change over time)³³ and to determine which of the identified Nash equilibria are evolutionarily stable (see “Methods”). Supplementary Figs. 11 and 12 provide a more specific representation of this scheme for the presented case studies in this paper