Date Published: February 17, 2004
Publisher: Public Library of Science
Author(s): Christopher V Rao, John R Kirby, Adam P Arkin
Abstract: Comparable processes in different species often involve homologous genes. One question is whether the network structure, in particular the feedback control structure, is also conserved. The bacterial chemotaxis pathways in E. coli and B. subtilis both regulate the same task, namely, excitation and adaptation to environmental signals. Both pathways employ many orthologous genes. Yet how these orthologs contribute to network function in each organism is different. To investigate this problem, we propose what is to our knowledge the first computational model for B. subtilis chemotaxis and compare it to previously published models for chemotaxis in E. coli. The models reveal that the core control strategy for signal processing is the same in both organisms, though in B. subtilis there are two additional feedback loops that provide an additional layer of regulation and robustness. Furthermore, the network structures are different despite the similarity of the proteins in each organism. These results demonstrate the limitations of pathway inferences based solely on homology and suggest that the control strategy is an evolutionarily conserved property.
Partial Text: Chemotaxis is the process by which motile bacteria sense changes in their chemical environment and move to more favorable conditions (Bren and Eisenbach 2000). In peritrichously flagellated bacteria such as Escherichia coli and Bacillus subtilis, swimming alternates between smooth runs and reorientating tumbles. Smooth runs require that the flagellar motors spin counterclockwise, whereas tumbles result from clockwise spins. Bacteria follow a random walk that is biased in the presence of gradients of attractants and repellents by alternating the frequency of runs and tumble. Owing to their small size, most bacteria are unable to sense chemical gradients across the length of their body. Rather, they respond only to temporal changes. In particular, their stimulated response always returns to prestimulus levels despite the sustained presence of attractants or repellents. Sensory adaptation involves a rudimentary form of memory that allows bacteria to compare their current and past environments. Bacteria regulate chemotaxis using a network of interacting proteins. The basic mechanism in flagellated bacteria involves receptor-mediated phosphorylation of a cytoplasmic protein (CheY) that binds to the flagellar motor and changes the spin direction (Falke et al. 1997). This pathway is characterized best in the γ-proteobacteria—E. coli and Salmonella enterica serovar typhimurium. Even though less is known about chemotaxis in other species of bacteria, the evidence so far suggests that the pathways are mechanistically different despite the homology of the individual genes to their γ-proteobacteria counterparts. B. subtilis, Helicobacter pylori, Myxococcus xanthus, Rhodobacter sphaeriodes, and Sinorhizobium meliloti, for example, all use similar yet distinct set of pathway components to regulate chemotaxis (Armitage and Schmitt 1997; Ward and Zusman 1999; Pittman et al. 2001; Sonenshein et al. 2002).
That the two pathways are different is not surprising, as E. coli and B. subtilis likely diverged over 1 billion years ago (Kunst et al. 1997). That both organisms use homologous genes is also not surprising. Divergent species of bacteria likely tinker with a limited set of genes, as mutations that change regulatory interactions between genes are far more frequent than mutations that confer novel function (Jacob 1977; Carroll et al. 2001). The genes may be similar, but how they interact with one another is different. In fact, other species of bacteria, each with their own idiosyncrasies, also have evolved novel chemotaxis pathways by tinkering with a small set of conserved genes and protein domains (see Table 2). The question then is whether other properties of the network, in addition to the genes, are conserved. The chemotaxis models for E. coli and B. subtilis indicate that the decision-making process is identical. The biochemistry is different, but the regulatory strategy is the same. Does this mean that regulation is conserved? Selective pressures likely constrain the evolution of most networks to ensure they function robustly despite intrinsic noise due to molecular fluctuations, stochastic gene expression, and mutation (Hartwell et al. 1999; von Dassow et al. 2000). Consequently, regulation becomes an indirect object of selection. As diverse physiological processes have equivalent regulatory needs such as homeostasis and adaptation, the underlying pathways, based on this hypothesis, involve identical control strategies.