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Open Access Highly Accessed Research article

Environmental versatility promotes modularity in genome-scale metabolic networks

Areejit Samal12, Andreas Wagner345* and Olivier C Martin16*

Author affiliations

1 Laboratoire de Physique Théorique et Modèles Statistiques, CNRS and Univ Paris-Sud, UMR 8626, F-91405 Orsay Cedex, France

2 Max Planck Institute for Mathematics in the Sciences, Inselstr. 22, 04103 Leipzig, Germany

3 Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland

4 Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Genopode, 1015 Lausanne, Switzerland

5 The Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA

6 INRA, UMR 0320/UMR 8120 Génétique Végétale, Univ Paris-Sud, F-91190 Gif-sur-Yvette, France

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Citation and License

BMC Systems Biology 2011, 5:135  doi:10.1186/1752-0509-5-135

Published: 24 August 2011

Abstract

Background

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.

Results

Using recently developed techniques to randomly sample large numbers of viable metabolic networks from a vast space of metabolic networks, we use flux balance analysis to study in silico metabolic networks that differ in their versatility. We find that highly versatile networks are also highly modular. They contain more modules and more reactions that are organized into modules. Most or all reactions in a module are associated with the same biochemical pathways. Modules that arise in highly versatile networks generally involve reactions that process nutrients or closely related chemicals. We also observe that the metabolism of E. coli is significantly more modular than even our most versatile networks.

Conclusions

Our work shows that modularity in metabolic networks can be a by-product of functional constraints, e.g., the need to sustain life in multiple environments. This organizational principle is insensitive to the environments we consider and to the number of reactions in a metabolic network. Because we observe this principle not just in one or few biological networks, but in large random samples of networks, we propose that it may be a generic principle of metabolic network organization.