Mesoscopic Biochemical Basis of Isogenetic Inheritance and Canalization: Stochasticity, Nonlinearity, and Emergent Landscape
Hong Qian; Hao Ge

Source MCB: Molecular & Cellular Biomechanics, Vol. 9, No. 1, pp. 1-30, 2012
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Keywords attractor; bistability; self-organization; single cell; stochastic gene expression, systems biology
Abstract Biochemical reaction systems in mesoscopic volume, under sustained environmental chemical gradient(s), can have multiple stochastic attractors. Two distinct mechanisms are known for their origins: (a) Stochastic single-molecule events, such as gene expression, with slow gene on-off dynamics; and (b) nonlinear networks with feedbacks. These two mechanisms yield different volume dependence for the sojourn time of an attractor. As in the classic Arrhenius theory for temperature dependent transition rates, a landscape perspective provides a natural framework for the system's behavior. However, due to the nonequilibrium nature of the open chemical systems, the landscape, and the attractors it represents, are all themselves emergent properties of complex, mesoscopic dynamics. In terms of the landscape, we show a generalization of Kramers' approach is possible to provide a rate theory. The emergence of attractors is a form of self-organization in the mesoscopic system; stochastic attractors in biochemical systems such as gene regulation and cellular signaling are naturally inheritable via cell division. Delbrück-Gillespie's mesoscopic reaction system theory, therefore, provides a biochemical basis for spontaneous isogenetic switching and canalization.
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