A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

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 alon

The Cost of Virulence: Retarded Growth of Salmonella Typhimurium Cells Expressing Type III Secretion System 1

Virulence factors generally enhance a pathogen's fitness and thereby foster transmission. However, most studies of pathogen fitness have been performed by averaging the phenotypes over large populations. Here, we have analyzed the fitness costs of virulence factor expression by Salmonella enterica subspecies I serovar Typhimurium in simple culture experiments. The type III secretion system ttss-1, a cardinal virulence factor for eliciting Salmonella diarrhea, is expressed by just a fraction of the S. Typhimurium population, yielding a mixture of cells that either express ttss-1 (TTSS-1+ phenotype) or not (TTSS-1− phenotype). Here, we studied in vitro the TTSS-1+ phenotype at the single cell level using fluorescent protein reporters. The regulator hilA controlled the fraction of TTSS-1+ individuals and their ttss-1 expression level. Strikingly, cells of the TTSS-1+ phenotype grew slower than cells of the TTSS-1− phenotype. The growth retardation was at least partially attributable to the expression of TTSS-1 effector and/or translocon proteins. In spite of this growth penalty, the TTSS-1+ subpopulation increased from <10% to approx. 60% during the late logarithmic growth phase of an LB batch culture. This was attributable to an increasing initiation rate of ttss-1 expression, in response to environmental cues accumulating during this growth phase, as shown by experimental data and mathematical modeling. Finally, hilA and hilD mutants, which form only fast-growing TTSS-1− cells, outcompeted wild type S. Typhimurium in mixed cultures. Our data demonstrated that virulence factor expression imposes a growth penalty in a non-host environment. This raises important questions about compensating mechanisms during host infection which ensure successful propagation of the genotype

Behavioral genetics and taste

This review focuses on behavioral genetic studies of sweet, umami, bitter and salt taste responses in mammals. Studies involving mouse inbred strain comparisons and genetic analyses, and their impact on elucidation of taste receptors and transduction mechanisms are discussed. Finally, the effect of genetic variation in taste responsiveness on complex traits such as drug intake is considered. Recent advances in development of genomic resources make behavioral genetics a powerful approach for understanding mechanisms of taste

Combining Tn-seq with comparative genomics identifies proteins uniquely essential in Shigella flexneri

Protein functions that are essential for the growth of bacterial pathogens provide promising targets for antibacterial treatment. This is especially true if those functions are uniquely essential for the pathogen, as this might allow the development of targeted antibiotics, i.e. those that disrupt essential functions only for the pathogenic bacteria. Here we present the results of a Tn-seq experiment designed to detect essential protein coding genes in Shigella flexneri 2a 2457T on a genome-wide scale. Our results suggest that 471 protein-coding genes in this organism are critical for cellular growth in rich media. Comparing this set of essential genes (the essential gene complement) with their orthologues in the closely related organism Escherichia coli K12 BW25113 revealed a significant number of genes that are essential in Shigella but not in E. coli, suggesting that the functional correspondence of these proteins had changed. Notably, we also identified a set of functionally related genes that are essential in Shigella but which have no orthologues in E. coli. We found an extreme bias in proteins that have evolved to provide essential functions, with many proteins essential in Shigella but not E. coli, but with none (or very few) being essential in E. coli but not Shigella. We also identify a set- of genes involved in nucleotide biosynthesis that are essential in Shigella, but which lack orthologues in E. coli. Consequently, the data presented here suggest that the essential gene complement can quickly become organism specific, especially for pathogenic organisms whose genomes might have reduced robustness in their metabolic capacity (e.g. functional redundancy), or a reduced numbers of protein coding genes. These results thus open the possibility of developing antibiotic treatments that target differentially essential genes, which may exist even between very closely related strains of bacteria

CHANGES of RESPONSE TO DOPAMINERGIC DRUGS in RATS SUBMITTED TO REM-SLEEP DEPRIVATION

ESCOLA PAULISTA MED,DEPT PSICOBIOL,RUA BOTUCATU 862,BR-04023 São Paulo,BRAZILESCOLA PAULISTA MED,DEPT PSICOBIOL,RUA BOTUCATU 862,BR-04023 São Paulo,BRAZILWeb of Scienc