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Delay-induced stochastic oscillations in gene regulation.

Authors :
Bratsun D
Volfson D
Tsimring LS
Hasty J
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Oct 11; Vol. 102 (41), pp. 14593-8. Date of Electronic Publication: 2005 Sep 30.
Publication Year :
2005

Abstract

The small number of reactant molecules involved in gene regulation can lead to significant fluctuations in intracellular mRNA and protein concentrations, and there have been numerous recent studies devoted to the consequences of such noise at the regulatory level. Theoretical and computational work on stochastic gene expression has tended to focus on instantaneous transcriptional and translational events, whereas the role of realistic delay times in these stochastic processes has received little attention. Here, we explore the combined effects of time delay and intrinsic noise on gene regulation. Beginning with a set of biochemical reactions, some of which are delayed, we deduce a truncated master equation for the reactive system and derive an analytical expression for the correlation function and power spectrum. We develop a generalized Gillespie algorithm that accounts for the non-Markovian properties of random biochemical events with delay and compare our analytical findings with simulations. We show how time delay in gene expression can cause a system to be oscillatory even when its deterministic counterpart exhibits no oscillations. We demonstrate how such delay-induced instabilities can compromise the ability of a negative feedback loop to reduce the deleterious effects of noise. Given the prevalence of negative feedback in gene regulation, our findings may lead to new insights related to expression variability at the whole-genome scale.

Details

Language :
English
ISSN :
0027-8424
Volume :
102
Issue :
41
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
16199522
Full Text :
https://doi.org/10.1073/pnas.0503858102