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.

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Journal Article

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Wang Z, Zhang J

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