A STUDY OF SMALL GENE REGULATORY NETWORKS: ROBUSTNESS, DYNAMICS, AND BEHAVIOR

Gene regulatory networks, like any evolving biological system, are subject to potentially damaging mutations. Much work has been done to study what types of networks are more robust to node deletions (knockouts of entire genes). Less well understood, however, is the question of which networks best maintain consistent behavior in the face of smaller mutations that affect binding affinity, protein half-life, and other regulatory parameters. Such mutations have subtler effects than whole-gene knockouts do, but because they are far more common than knockout mutations, their impact on network evolution may be substantial. The first chapter investigates the expression patterns of simulated gene regulatory networks as these types of parameters are varied, and explores which topologies allow the networks to "ignore " parameter-changing mutations and maintain their expression patterns relatively unchanged. In the simulations, networks containing mutual repression feedback consistently displayed a more robust response to simulated mutation. The presence of this variety of feedback in well-studied developmental regulatory networks suggests that it may be a widespread mechanism for reducing the phenotypic consequences of both noise an