Parameter asymmetry and time-scale separation in core genetic commitment circuits

Abstract

Theory allows studying why Evolution might select core genetic commitment circuit topologies over alternatives. The nonlinear dynamics of the underlying gene regulation together with the unescapable subtle interplay of intrinsic biochemical noise impact the range of possible evolutionary choices. The question of why certain genetic regulation circuits might present robustness to phenotype-delivery breaking over others, is therefore of high interest. Here, the behavior of systematically more complex commitment circuits is studied, in the presence of intrinsic noise, with a focus on two aspects relevant to biology: parameter asymmetry and time-scale separation. We show that phenotype delivery is broken in simple two- and three-gene circuits. In the two-gene circuit, we show how stochastic potential wells of different depths break commitment. In the three-gene circuit, we show that the onset of oscillations breaks the commitment phenotype in a systematic way. Finally, we also show that higher dimensional circuits (four-gene and five-gene circuits) may be intrinsically more robust.

Graphical abstract

Keywords

systems biology / theoretical biology / gene regulation / nonlinear dynamics / stochasticity

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