Abstract
BACKGROUND: Metabolic dependencies between microbial species have a significant impact on the assembly and activity of microbial communities. However, the evolutionary origins of such dependencies and the impact of metabolic and genomic architecture on their emergence are not clear. RESULTS: To address these questions, we developed a novel framework, coupling a reductive evolution model with a multi-species genome-scale metabolic model to simulate the evolution of two-species microbial communities. Simulating thousands of independent evolutionary trajectories, we surprisingly found that under certain environmental and evolutionary settings metabolic dependencies emerged frequently even though our model does not include explicit selection for cooperation. Evolved dependencies involved cross-feeding of a diverse set of metabolites, reflecting constraints imposed by metabolic network architecture. We additionally found metabolic 'missed opportunities', wherein species failed to capitalize on metabolites made available by their partners. Examining the genes deleted in each evolutionary trajectory and the deletion timing further revealed both genome-wide properties and specific metabolic mechanisms associated with species interaction. CONCLUSION: Our findings provide insight into the evolution of cooperative interaction among microbial species and a unique view into the way such relationships emerge.