constitutive versus responsive gene expression strategies for growth in changing environments本构和响应基因的表达策略在变化的环境中成长.pdfVIP

Constitutive versus Responsive Gene Expression Strategies for Growth in Changing Environments Nico Geisel* Departament de Fisica Fonamental, Facultat de Fisica, Universitat de Barcelona, Barcelona, Spain 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 stra