 Environmental Statistics and Optimal RegulationDavid A Sivak and Matt Thomson PLOS Computational Biology, 2014, vol. 10, issue 9, 1-12 Abstract: Any organism is embedded in an environment that changes over time. The timescale for and statistics of environmental change, the precision with which the organism can detect its environment, and the costs and benefits of particular protein expression levels all will affect the suitability of different strategies–such as constitutive expression or graded response–for regulating protein levels in response to environmental inputs. We propose a general framework–here specifically applied to the enzymatic regulation of metabolism in response to changing concentrations of a basic nutrient–to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, respectively, and the costs associated with enzyme production. We use this framework to address three fundamental questions: (i) when a cell should prefer thresholding to a graded response; (ii) when there is a fitness advantage to implementing a Bayesian decision rule; and (iii) when retaining memory of the past provides a selective advantage. We specifically find that: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones.Author Summary: All organisms live in environments that dynamically change in ways that are only partially predictable. The seasons, diurnal cycles, oceanic fluid dynamics, and the progression of food through the human gut, all impose some predictability on common microbial ecosystems. Microbes are also at the whim of random processes (like thermal motion) that introduce uncertainty into environmental change. Here, we develop a theoretical framework to analyze how cellular regulatory systems might balance this predictability and uncertainty to most effectively respond to a dynamic environment. We model a simple cellular goal: regulating a single enzyme to maximize the energy generated from a nutrient whose environmental concentration varies. In this context, optimal regulatory strategies are determined by an uncertainty ratio comparing cellular measurement noise and environmental variability. Intermediate levels of uncertainty call for sophisticated Bayesian decision rules, where selective advantage accrues to organisms that incorporate past experience in their inference of the current environmental state. When uncertainty is either high or low, optimal signal processing strategies are comparatively simple: constitutive expression or naive tracking, respectively. This work provides a theoretical basis for interpreting molecular signal processing algorithms and suggests that relative levels of environmental variability and cellular noise affect how microbes should process information. Date: 2014 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1003826 DOI: 10.1371/journal.pcbi.1003826 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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