Abstract
BackgroundThe regulatory feedback loops that present in structural and functional organization of molecular-genetic systems and the phenomenon of the regulatory signal delay, a time period between the moment of signal reception and its implementation, provide natural conditions for complicated dynamic regimes in these systems. The delay phenomenon at the intracellular level is a consequence of the matrix principle of data transmission, implemented through the rather complex processes of transcription and translation.However, the rules of the influence of system structure on system dynamics are not clearly understood. Knowledge of these rules is particularly important for construction of synthetic gene networks with predetermined properties.ResultsWe study dynamical properties of models of simplest circular gene networks regulated by negative feedback mechanisms. We have shown existence and stability of oscillating trajectories (cycles) in these models. Two algorithms of construction and localization of these cycles have been proposed. For one of these models, we have solved an inverse problem of parameters identification.ConclusionsThe modeling results demonstrate that non-stationary dynamics in the models of circular gene networks with negative feedback loops is achieved by a high degree of non-linearity of the mechanism of the autorepressor influence on its own expression, by the presence of regulatory signal delay, the value of which must exceed a certain critical value, and transcription/translation should be initiated from a sufficiently strong promoter/Shine-Dalgarno site. We believe that the identified patterns are key elements of the oscillating construction design.
Highlights
IntroductionMolecular-genetic systems or gene networks are molecular machines which decode genetic programs and bring them up to all the levels of living systems organization, from the molecular level (metabolic networks, signaling pathways, splicing, transport etc.) to subcellular, cellular, tissue, and organismic one
Molecular-genetic systems or gene networks are molecular machines which decode genetic programs and bring them up to all the levels of living systems organization, from the molecular level to subcellular, cellular, tissue, and organismic one
We believe that the identified patterns are key elements of the oscillating construction design
Summary
Molecular-genetic systems or gene networks are molecular machines which decode genetic programs and bring them up to all the levels of living systems organization, from the molecular level (metabolic networks, signaling pathways, splicing, transport etc.) to subcellular, cellular, tissue, and organismic one During the evolution, these systems have obtained ability to adequate reaction on the external signals and on changing of the environmental conditions. Configuration of loops with negative feedback loops regulation is more simple task for a cell, than that of loops with positive feedback loops, because it can be accomplished by a simple blockage of the transcription initiation site by the regulatory protein without formation of complex structures that interact with the RNA polymerase This type of regulation is widespread in nature, and its simplest example is a subsystem containing just one gene which controls its own expression by negative feedback mechanism. Knowledge of these rules is important for construction of synthetic gene networks with predetermined properties
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