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Abstract
Microbes respond to changing environments by adjusting gene expression levels to the demand for the corresponding proteins. Adjusting protein levels is slow, consequently cells may reach the optimal protein level only by a time when the demand changed again. It is therefore not a priori clear whether expression “on demand” is always the optimal strategy. Indeed, many genes are constitutively expressed at intermediate levels, which represents a permanent cost but provides an immediate benefit when the protein is needed. Which are the conditions that select for a responsive or a constitutive expression strategy, what determines the optimal constitutive expression level in a changing environment, and how is the fitness of the two strategies affected by gene expression noise? Based on an established model of the lac- and gal-operon expression dynamics, we study the fitness of a constitutive and a responsive expression strategy in time-varying environments. We find that the optimal constitutive expression level differs from the average demand for the gene product and from the average optimal expression level; depending on the shape of the growth rate function, the optimal expression level either provides intermediate fitness in all environments, or maximizes fitness in only one of them. We find that constitutive expression can provide higher fitness than responsive expression even when regulatory machinery comes at no cost, and we determine the minimal response rate necessary for “expression on demand” to confer a benefit. Environmental and inter-cellular noise favor the responsive strategy while reducing fitness of the constitutive one. Our results show the interplay between the demand-frequency for a gene product, the genetic response rate, and the fitness, and address important questions on the evolution of gene regulation. Some of our predictions agree with recent yeast high throughput data, for others we propose the experiments that are needed to verify them.
Highlights
In natural environments cells are frequently facing variable conditions, to which they must adapt in order to maximize growth and survival
The focus of this article is to understand how environmental factors determine the optimal constitutive expression levels that maximizes net growth in a changing environment, and to understand why and under which conditions constitutive expression confers a growth advantage compared to regulated, responsive expression. To answer these questions we propose a model that builds on previously established descriptions of the lac- and gal- operon expression dynamics [17,22,30], and compare the time-averaged growth rates of both strategies in a two-state environment, taking account of environmental and inter-cellular noise
It is a general belief that responding to an environmental change is better than not responding
Summary
In natural environments cells are frequently facing variable conditions, to which they must adapt in order to maximize growth and survival. Understanding microbial behaviors in changing environments provides insights into the evolution in natural habitats where the physiologic demands are constantly changing [1,2,3]. Manipulation of these strategies can be relevant in industrial processing, e.g. fermentation [4], antibiotic therapies [5] and biotechnological process optimization. A particular phenotype provides a growth or survival advantage in one environmental condition, but is maladapted in other environments. When lactose is the only energy source, in turn, production of lacZ enhances growth [16,19,20]
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