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Abundant indispensable redundancies in cellular metabolic networks.

ABSTRACT: Cellular life is a highly redundant complex system; yet, the evolutionary maintenance of the redundancy remains unexplained. Using a systems biology approach, we infer that 37-47% of metabolic reactions in Escherichia coli and yeast can be individually removed without blocking the production of any biomass component under any nutritional condition. However, the majority of these redundant reactions are preserved because they have differential maximal efficiencies at different conditions or their loss causes an immediate fitness reduction that can only be regained via mutation, drift, and selection in evolution. The remaining redundancies are attributable to pleiotropic effects or recent horizontal gene transfers. We find that E. coli and yeast exhibit opposite relationships between the functional importance and redundancy level of a reaction, which is inconsistent with the conjecture that redundancies are preserved as an adaptation to back up important parts in the system. Interestingly, the opposite relationships can both be recapitulated by a simple model in which the natural environments of the organisms change frequently. Thus, adaptive backup is neither necessary nor sufficient to explain the high redundancy of cellular metabolic networks. Taken together, our results strongly suggest that redundant reactions are not kept as backups and that the genetic robustness of metabolic networks is an evolutionary by-product.

SUBMITTER: Wang Z

PROVIDER: S-EPMC2817398 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Abundant indispensable redundancies in cellular metabolic networks.

Wang Zhi Z Zhang Jianzhi J

Genome biology and evolution 20090430

Cellular life is a highly redundant complex system; yet, the evolutionary maintenance of the redundancy remains unexplained. Using a systems biology approach, we infer that 37-47% of metabolic reactions in Escherichia coli and yeast can be individually removed without blocking the production of any biomass component under any nutritional condition. However, the majority of these redundant reactions are preserved because they have differential maximal efficiencies at different conditions or their ...[more]

PMID: 20333174

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Project description:BackgroundThe experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity.Methodology/principal findingsIn order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network.Conclusions/significanceWe have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably retain these modifications. Here for the first time, we have introduced the general concept of attractor metabolic network, in which this dynamic behavior is observed.

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Abundant indispensable redundancies in cellular metabolic networks.

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Abundant indispensable redundancies in cellular metabolic networks.

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