Beyond topology: coevolution of structure and flux in metabolic networks

Interactions between the structure of a metabolic network and its functional properties underlie its evolutionary diversification, but the mechanism by which such interactions arise remains elusive. Particularly unclear is whether metabolic fluxes that determine the concentrations of compounds produced by a metabolic network, are causally linked to a network's structure or emerge independently of it. A direct empirical study of populations where both structural and functional properties vary among individuals' metabolic networks is required to establish whether changes in structure affect the distribution of metabolic flux. In a population of house finches (Haemorhous mexicanus), we reconstructed full carotenoid metabolic networks for 442 individuals and uncovered 11 structural variants of this network with different compounds and reactions. We examined the consequences of this structural diversity for the concentrations of plumage-bound carotenoids produced by flux in these networks. We found that concentrations of metabolically derived, but not dietary carotenoids, depended on network structure. Flux was partitioned similarly among compounds in individuals of the same network structure: within each network, compound concentrations were closely correlated. The highest among-individual variation in flux occurred in networks with the strongest among-compound correlations, suggesting that changes in the magnitude, but not the distribution of flux, underlie individual differences in compound concentrations on a static network structure. These findings indicate that the distribution of flux in carotenoid metabolism closely follows network structure. Thus, evolutionary diversification and local adaptations in carotenoid metabolism may depend more on the gain or loss of enzymatic reactions than on changes in flux within a network structure.