Role of Translational Coupling in Robustness of Bacterial Chemotaxis Pathway

Linda Løvdok,Dirk Lebiedz,Ferencz S Pop,Markus Kollmann,Anette Müller,Victor Sourjik,Kajetan Bentele,Nikita Vladimirov

doi:10.1371/journal.pbio.1000171

Abstract

Author SummaryAll cellular networks are subject to fluctuations in the levels of their components. Robustness of the network output in the face of stochastic gene expression, or gene expression noise, is therefore essential to ensure proper function. Selection for robustness might thus have shaped much of the cellular evolution. We have used Escherichia coli chemotaxis, one of the most thoroughly studied model systems for signal transduction, to analyze the role of gene organization in robustness. Our mathematical modeling predicted that coupling the expression of chemotaxis proteins with opposing functions should buffer the output of the signaling pathway against stochastic variations in protein production. Consistent with this model, protein coexpression was indeed observed to improve chemotaxis and to be under selection during chemotaxis-driven spreading of a cell population. We show that tight coexpression is ensured by both transcriptional and translational gene coupling. We conclude that evolutionary selection for pathway robustness in the presence of gene expression noise can explain, not only the polycistronic organization of chemotaxis genes, but also the gene order within chemotaxis operons. Selection on the gene order was further confirmed by the observation of a strong bias towards specific pairwise occurrences of chemotaxis genes in sequenced prokaryotic genomes.

Highlights

Any intracellular network is permanently exposed to a wide range of intra- and extracellular perturbations that affect levels of components and reaction rates
Strong correlation in the single-cell levels of individual chemotaxis proteins has been observed in E. coli, and the chemotaxis pathway was shown to be primarily robust against such concerted variation [7]
Ribosomes translating the upstream gene will unwind any secondary structure of the mRNA that might form around the SD sequence of the downstream gene, as long as this sequence belongs to the translated region of the upstream gene

Summary

Introduction

Any intracellular network is permanently exposed to a wide range of intra- and extracellular perturbations that affect levels of components and reaction rates. Both eukaryotic and prokaryotic systems have evolved mechanisms that allow them to produce a robust output under varying conditions. The pathway includes transmembrane receptors ( called methyl-accepting chemotaxis proteins, or MCPs) of five types, the receptor-coupled kinase CheA, the adaptor CheW, the response regulator CheY, and the phosphatase CheZ, as well as the adaptation system that consists of two opposing receptor modification enzymes, the methyltransferase CheR and the methylesterase CheB. CheA autophosphorylation activity is controlled by ligand binding to receptors, with CheW needed to couple CheA to receptors. Cells adapt to a constant stimulation by adjusting levels of receptor methylation, with higher methylated receptors being more efficient in kinase activation

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Discussion

Conclusion