Abstract

Metabolic cooperation between two cell types is a common observation in many bacteria studies. However, this same type of interaction is less well observed in eukaryotes. Using the eukaryotic model organism, budding yeast, we find that colonies have an abundance of metabolites in the extra-­cellular space and in addition, prefer to uptake these metabolites over self­-synthesising them. We established a yeast colony which gradually develops metabolic deficiencies in amino acid and nucleobase metabolism. Allowing its self­-establishment, colony cells were able to enter an efficient state of cooperation to overcome their metabolic deficiencies. We therefore conclude that the bottleneck of metabolic cooperation is found in community structure. The established community reacted flexibly to changes in nutrition, and displayed non random distribution of cell types, indicating a partitioning of metabolic roles between cells. On the single cell level, we find metabolic specialisation to be causally linked to cell­-cell heterogeneity in response to heat and oxidative stress. Metabolic cooperation is therefore effective in eukaryotes but is dependent on specific community structures to impose spatial and physiological diversification among single, cooperating cells.