Genetic Regulatory Mechanisms and the Ecological Niche of Escherichia coli

Abstract

Whether the regulatory protein of an inducible operon for a catabolic pathway is a positive or a negative element in the control of expression is correlated with the frequent or infrequent presence, respectively, of the system's substrate in the natural environment.In several of the best-studied inducible operons of enteric bacteria, the regulatory protein acts as a negative (repressor) element in the control of gene expression. Examples are the galactose (1), glycerol (2), histidine utilization (3), and lactose (4) operons. In other well-studied inducible operons, like arabinose (5), maltose (6), and rhamnose (7), the regulatory protein is a positive (activator) element. These differences are represented schematically in Fig. 1. I will show that one can analyze the functional implications of these differences and predict that galactose, glycerol, histidine, and lactose are seldom in the organism's natural environment, whereas arabinose, maltose, and rhamnose are frequently present there. These predictions are confirmed by the absorption patterns for these substances in the mammalian intestine.The relative merits of genetic control by repressors and activators undoubtedly have been considered by many investigators. However, there have been no systematic attempts to compare these mechanisms on the basis of function and thus explore the reasons for their selection in nature. Clearly, the two types of mechanisms respond in opposite ways to mutations affecting (i) the synthesis of regulator, (ii) the degradation of regulator, and (iii) the mutual recognition of regulator and its binding site on the DNA. But there could be other functional differences, not necessarily intuitively obvious, responsible for the selection of these types of mechanisms. To examine this possibility one cannot compare directly two systems like the lactose and arabinose operons because of all their differences that are irrelevant to the comparison of the control mechanisms per se. Ideally, one would like a controlled comparison in which the two systems are identical in every respect except for the differences in the type of control mechanism utilized. Although this is difficult to do experimentally, it can be simulated by appropriate mathematical analysis. I have carried out such an analysis, which confirms the obvious behavioral differences mentioned above, but more importantly suggests that they are the only inherent differences between repressor and activator control (8). Therefore, it is these three kinds of mutations that must be examined further if we are to understand the natural selection of genetic control mechanisms. Natural mutational tendenciesOf the possible mutations affecting the synthesis and degradation of regulatory proteins, those that reduce the rate of synthesis and those that increase the rate of degradation presumably are the most common. It is reasonable to expect that only certain specific nucleotide sequences can result in a promoter with increased efficiency, whereas many different sequences could be promo...

Genetic Analysis of the Histidine Utilization (hut) Genes in Pseudomonas fluorescens SBW25

“…Drawing upon Savageau's demand theory of regulatory control (Savageau 1974(Savageau , 1989(Savageau , 1998, negative regulation indicates that the hut operon is infrequently used and that histidine is scarce in the natural environment of this bacterium. Indeed, the scarcity of histidine in the plant rhizosphere has previously been shown (Zhang et al 2006) and is also indicated here.…”

Evolutionary selection between alternative modes of gene regulation

“…The proposed qualitative principle calls for a quantitative theoretical formulation and analysis, as recognized already in the original work of Savageau (2). Indeed, a more recent theoretical study by Savageau (5) yielded some support for an evolutionary choice of repressors at low demand and activators at high demand.…”

“…However, different designs can be functionally equivalent. Already 30 years ago, Savageau raised the fundamental question of whether nature's choice between functionally equivalent module designs is random or whether there is an evolutionary selection criterion (2,3). This question was posed in the context of a simple genetic switch, the elementary unit of gene regulatory modules.…”

“…A basic function of a genetic switch is to assure that the expression of a specific gene is turned on when a signal, e.g., a nutrient, is present and turned off when the signal is absent. Importantly, the presence of the signal may vary on long time scales, e.g., a population of Escherichia coli cells can use lactose as the carbon source in a mammalian infant, but lactose may then become unavailable for a long time in the same host (2). The desired regulatory function can be implemented by a double-positive (++) mode of control, e.g., the signal activates a transcription factor that then activates the gene (Fig.…”

“…Savageau empirically examined many bacterial genetic switches for correlations between the mode of gene regulation and temporal patterns in the input signal (2,3). The latter were estimated, for instance, from physiological measurements of nutrient absorption rates in the mammalian intestine, which are an indication for the likelihood that a specific nutrient reaches the colon where E. coli colonizes.…”