Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alone.
BackgroundIn this study, we aimed at investigating heterogeneity in the expression of metabolic genes in clonal populations of Escherichia coli growing on glucose as the sole carbon source. Different metabolic phenotypes can arise in these clonal populations through variation in the expression of glucose transporters and metabolic enzymes. First, we focused on the glucose transporters PtsG and MglBAC to analyze the diversity of glucose uptake strategies. Second, we analyzed phenotypic variation in the expression of genes involved in gluconeogenesis and acetate scavenging (as acetate is formed and excreted during bacterial growth on glucose), which can reveal, for instance, phenotypic subpopulations that cross-feed through the exchange of acetate. In these experiments, E. coli MG1655 strains containing different transcriptional GFP reporters were grown in chemostats and reporter expression was measured with flow cytometry.ResultsOur results suggest heterogeneous expression of metabolic genes in bacterial clonal populations grown in glucose environments. The two glucose transport systems exhibited different level of heterogeneity. The majority of the bacterial cells expressed the reporters for both glucose transporters MglBAC and PtsG and a small fraction of cells only expressed the reporter for Mgl. At a low dilution rate, signals from transcriptional reporters for acetyl-CoA synthetase Acs and phosphoenolpyruvate carboxykinase Pck indicated that almost all cells expressed the genes that are part of acetate utilization and the gluconeogenesis pathway, respectively. Possible co-existence of two phenotypic subpopulations differing in acs expression occurred at the threshold of the switch to overflow metabolism. The overflow metabolism results in the production of acetate and has been previously reported to occur at intermediate dilution rates in chemostats with high concentration of glucose in the feed.ConclusionsAnalysis of the heterogeneous expression of reporters for genes involved in glucose and acetate metabolism raises new question whether different metabolic phenotypes are expressed in clonal populations growing in continuous cultures fed on glucose as the initially sole carbon source.
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