4.4 Article

Simulating the evolution of signal transduction pathways

Journal

JOURNAL OF THEORETICAL BIOLOGY
Volume 241, Issue 2, Pages 223-232

Publisher

ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2005.11.024

Keywords

computational simulation; signal transduction networks; evolution; chemotaxis; network modeling

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We use a generic model of a network of proteins that can activate or deactivate each other to explore the emergence and evolution of signal transduction networks and to gain a basic understanding of their general properties. Starting with a set of non-interacting proteins, we evolve a signal transduction network by random mutation and selection to fulfill a complex biological task. In order to validate this approach we base selection on a fitness function that captures the essential features of chemotactic behavior as seen in bacteria. We find that a system of as few as three proteins can evolve into a network mediating chemotaxis-like behavior by acting as a derivative sensor. Furthermore, we find that the dynamics and topology of such networks show many similarities to the natural chemotaxis pathway, that the response magnitude can increase with increasing network size and that network behavior shows robustness towards variations in some of the internal parameters. We conclude that simulating the evolution of signal transduction networks to mediate a certain behavior may be a promising approach for understanding the general properties of the natural pathway for that behavior. (c) 2005 Elsevier Ltd. All rights reserved.

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