Signatures of Arithmetic Simplicity in Metabolic Network Architecture


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Show simple item record Riehl, William J. en_US Krapivsky, Paul L. en_US Redner, Sidney en_US Segrè, Daniel en_US 2012-01-11T00:41:23Z 2012-01-11T00:41:23Z 2010-4-1 en_US
dc.identifier.citation Riehl, William J., Paul L. Krapivsky, Sidney Redner, Daniel Segrè. "Signatures of Arithmetic Simplicity in Metabolic Network Architecture" PLoS Computational Biology 6(4): e1000725. (2010) en_US
dc.identifier.issn 1553-7358 en_US
dc.description.abstract Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that properties similar to those predicted for the artificial chemistry hold also for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity. Author Summary Metabolism is the network of biochemical reactions that transforms available resources ("inputs") into energy currency and building blocks ("outputs"). Different organisms have different assortments of metabolic pathways and input/output requirements, reflecting their adaptation to specific environments, and to specific strategies for reproduction and survival. Here we ask whether, beneath the intricate wiring of these networks, it is possible to discern signatures of optimal (i.e., shortest and maximally efficient) pathway architectures. A systematic search for such optimal pathways between all possible pairs of input and output molecules in real organic chemistry is computationally intractable. However, we can implement such a search in a simple artificial chemistry, which roughly resembles a single atom (e.g., carbon) version of real biochemistry. We find that optimal pathways in our idealized chemistry display a logarithmic dependence of pathway length on input/output molecule size. They also display recurring topologies, including autocatalytic cycles reminiscent of ancient and highly conserved cores of real biochemistry. Finally, across all optimal pathways, we identify universally important metabolites and reactions, as well as a characteristic distribution of reaction utilization. Similar features can be observed in real metabolic networks, suggesting that arithmetic simplicity may lie beneath some aspects of biochemical complexity. en_US
dc.description.sponsorship Office of Science; U.S. Department of Energy (DE-FG02-07ER64388), NASA (NASA Astrobiology Institute, NNA08CN84A), National Science Foundation (NSF DMR0535503, DMR0906504, NSF CCF-0829541) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Riehl et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Signatures of Arithmetic Simplicity in Metabolic Network Architecture en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pcbi.1000725 en_US
dc.identifier.pubmedid 20369010 en_US
dc.identifier.pmcid 2848538 en_US

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