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Fundamental limits on the suppression of molecular fluctuations.

ABSTRACT: Negative feedback is common in biological processes and can increase a system's stability to internal and external perturbations. But at the molecular level, control loops always involve signalling steps with finite rates for random births and deaths of individual molecules. Here we show, by developing mathematical tools that merge control and information theory with physical chemistry, that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctuations. Specifically, the minimum standard deviation in abundances decreases with the quartic root of the number of signalling events, making it extremely expensive to increase accuracy. Our results are formulated in terms of experimental observables, and existing data show that cells use brute force when noise suppression is essential; for example, regulatory genes are transcribed tens of thousands of times per cell cycle. The theory challenges conventional beliefs about biochemical accuracy and presents an approach to the rigorous analysis of poorly characterized biological systems.

SUBMITTER: Lestas I

PROVIDER: S-EPMC2996232 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Fundamental limits on the suppression of molecular fluctuations.

Lestas Ioannis I Vinnicombe Glenn G Paulsson Johan J

Nature 20100901 7312

Negative feedback is common in biological processes and can increase a system's stability to internal and external perturbations. But at the molecular level, control loops always involve signalling steps with finite rates for random births and deaths of individual molecules. Here we show, by developing mathematical tools that merge control and information theory with physical chemistry, that seemingly mild constraints on these rates place severe limits on the ability to suppress molecular fluctu ...[more]

PMID: 20829788

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Project description:Parasitoid wasps are increasingly being used to control insect pest populations, where the pest is the host species parasitized by the wasp. Here we use the discrete-time formalism of the Nicholson-Bailey model to investigate a fundamental question-are there limits to parasitoid-driven suppression of the host population density while still ensuring a stable coexistence of both species? Our model formulation imposes an intrinsic self-limitation in the host's growth resulting in a carrying capacity in the absence of the parasitoid. Different versions of the model are considered with parasitism occurring at a developmental stage that is before, during, or after the growth-limiting stage. For example, the host's growth limitation may occur at its larval stage due to intraspecific competition, while the wasps attack either the host egg, larval or pupal stage. For slow-growing hosts, models with parasitism occurring at different life stages are identical in terms of their host suppression dynamics but have contrasting differences for fast-growing hosts. In the latter case, our analysis reveals that wasp parasitism occurring after host growth limitation yields the lowest pest population density conditioned on stable host-parasitoid coexistence. For ecologically relevant parameter regimes we estimate this host suppression to be roughly 10-20% of the parasitoid-free carrying capacity. We further expand the models to consider a fraction of hosts protected from parasitism (i.e., a host refuge). Our results show that for a given host reproduction rate there exists a critical value of protected host fraction beyond which, the system dynamics are stable even for high levels of parasitism that drive the host to arbitrary low population densities. In summary, our systematic analysis sheds key insights into the combined effects of density-dependence in host growth and parasitism refuge in stabilizing the host-parasitoid population dynamics with important implications for biological control.

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Fundamental limits on the suppression of molecular fluctuations.

Publications

Fundamental limits on the suppression of molecular fluctuations.

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