Proteome allocation and the evolution of metabolic cross-feeding

Metabolic cross-feeding (MCF) is a widespread type of ecological interaction where organisms share nutrients. In a common instance of MCF, an organism incompletely metabolises sugars and releases metabolites that are used by another as a carbon source to produce energy. Why would the former waste edible food, and why does this preferentially occur at specific locations in the sugar metabolic pathway (acetate and glycerol are preferentially exchanged) have challenged evolutionary theory for decades. Addressing these questions requires to model the cellular features involved; to this end, we built an explicit model of metabolic reactions, including their enzyme-driven catalysis and the cellular constraints acting on the proteome that may incur a cost to expressing all enzymes along a pathway. After showing that cells should in principle prioritise upstream reactions when metabolites are restrained inside the cell, we investigate how the diffusivity of these metabolites may trigger the emergence of MCF in a population. We find that the occurrence of MCF is rare and requires that an intermediate metabolite be extremely diffusive: indeed, up to high membrane permeability coefficients, the expected evolutionary outcome is not a diversification that resembles MCF but a single genotype that instead overexpresses downstream enzymes. Only at very high levels of membrane permeability and under distinctive sets of parameters should the population diversify and MCF evolve. These results help understand the origins of simple microbial communities, and may later be extended to investigate how evolution has progressively built up todays extremely diverse communities. Significance statementCan two species thrive on a single energetic resource? While the competitive exclusion principle predicts that one in the pair should go extinct, it may occur that an organism releases partly metabolised molecules in the environment, securing an ecological niche for a second organism in a specialisation process called metabolic cross-feeding. Here we investigate how evolution may favor the waste of a useful resource using a model that considers how a cell packed with proteins may be less efficient, hence favoring a shortening of metabolic pathways in order to reduce cell packing. Our model indicates that such specialisation only occurs under restricted conditions. Incidentally, this makes the signatures of cross-feeding, such as which metabolites are preferentially involved, quite predictable.