Bifurcation and Oscillatory Dynamics of Delayed Cyclic Gene Networks Including Small RNAs.

Abstract

It has been demonstrated in a large number of experimental results that small RNAs (sRNAs) play a vital role in gene regulation processes. Thus, the gene regulation process is dominated by sRNAs in addition to messenger RNAs and proteins. However, the regulation mechanism of sRNAs is not well understood and there are few models considering the effect of sRNAs. So it is of realistic biological background to include sRNAs when modeling gene networks. In this paper, sRNAs are incorporated into the process of gene expression and a new differential equation model is put forward to describe cyclic genetic regulatory networks with sRNAs and multiple delays. We mainly investigate the stability and bifurcation criteria for two cases: 1) positive cyclic genetic regulatory networks and 2) negative cyclic genetic regulatory networks. For a positive cyclic genetic regulatory network, it is revealed that there may exist more than one equilibrium and the multistability can appear. Sufficient conditions are established for the delay-independent stability and fold bifurcations. It is found that the dynamics of positive cyclic gene networks has no bearing on time delays, but depends on the biochemical parameters, the Hill coefficient and the equilibrium itself. For a negative cyclic genetic regulatory network, it is proved that there exists a unique equilibrium. Delay-dependent conditions for the stability are derived, and the existence of Hopf bifurcations is examined. Different from the delay-independent stability of positive gain networks, the stability of equilibrium is determined not only by the biochemical parameters, the Hill coefficient and the equilibrium itself, but also by the total delay. At last, three illustrative examples are provided to validate the major results.