Environmental versatility promotes modularity in genome-scale metabolic networks

TL;DR

This paper investigates whether the need for metabolic networks to operate in multiple chemical environments promotes the development of modular structures, suggesting environmental versatility as a key factor in metabolic modularity.

Contribution

It introduces a new definition of modules based on reaction coupling and explores how environmental versatility influences metabolic network modularity.

Findings

Metabolic modules are defined by fully coupled reactions.

Versatile metabolic networks tend to be more modular.

Environmental versatility correlates with increased modularity.

Abstract

The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chemical environments. For such networks, we define a network module as a maximal set of reactions that are fully coupled, i.e., whose fluxes can only vary in fixed proportions. This definition overcomes limitations of purely graph based analyses of metabolism by exploiting the functional links between reactions. We call a metabolic network viable in a given chemical environment if it can synthesize all of an organism's biomass compounds from nutrients in this environment. An organism's metabolism is highly versatile if it can sustain life in many different chemical environments. We here ask whether versatility affects the modularity of metabolic networks.