Stoichiometric design of metabolic networks: multifunctionality,clusters, optimization,weak and strong robustness |
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Authors: | Ebenhöh Oliver Heinrich Reinhart |
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Institution: | (1) Department of Theoretical Biophysics, Institute of Biology, Humboldt-University, Invalidenstra×e 42, 10115 Berlin, Germany |
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Abstract: | Starting from a limited set of reactions describing changes in the carbon skeleton of biochemical compounds complete sets
of metabolic networks are constructed. The networks are characterized by the number and types of participating reactions.
Elementary networks are defined by the condition that a specific chemical conversion can be performed by a set of given reactions
and that this ability will be lost by elimination of any of these reactions. Groups of networks are identified with respect
to their ability to perform a certain number of metabolic conversions in an elementary way which are called the network’s
functions. The number of the network functions defines the degree of multifunctionality. Transitions between networks and
mutations of networks are defined by exchanges of single reactions. Different mutations exist such as gain or loss of function
mutations and neutral mutations. Based on these mutations neighbourhood relations between networks are established which are
described in a graph theoretical way. Basic properties of these graphs are determined such as diameter, connectedness, distance
distribution of pairs of vertices. A concept is developed to quantify the robustness of networks against changes in their
stoichiometry where we distinguish between strong and weak robustness. Evolutionary algorithms are applied to study the development
of network populations under constant and time dependent environmental conditions. It is shown that the populations evolve
toward clusters of networks performing a common function and which are closely neighboured. Under changing environmental conditions
multifunctional networks prove to be optimal and will be selected. |
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