Augix Guohua XU's List: Journal Club

• Phages are the most abundant entity in the biosphere and outnumber bacteria by a factor of 10. Phage DNA may also constitute 20% of bacterial genomes
• we explore the impact of cryptic prophages on cell physiology by precisely deleting all nine prophage elements (166 kbp) using Escherichia coli
• We find that cryptic prophages contribute significantly to resistance to sub-lethal concentrations of quinolone and β-lactam antibiotics primarily through proteins that inhibit cell division
• The well-studied Escherichia coli K-12 has gained 1,600 kbp of novel DNA (18%) since its divergence from Salmonella sp. 100 million years ago⁵ and contains nine cryptic prophage elements, which comprise 3.6% of its genome
• Our goal here was to begin to understand the evolutionary importance of cryptic prophage elements by exploring the function of prophage genes on cell physiology. To this end, we created a single E. coli strain, Δ9, that lacks all nine cryptic prophages (CP4-6, DLP12, e14, rac, Qin, CP4-44, CPS-53, CPZ-55 and CP4-57); each prophage was removed precisely using a method that leaves one attachment site and mimics natural excision.
• Two systems biology tools, phenotype and DNA microarrays, were then used to identify the altered phenotypes and to elucidate the important prophage genes responsible for the changes in the phenotypes.
• we determined that the poorly studied cryptic prophage genes increased growth, provided protection for quinolone and β-lactam antibiotics, increased resistance to osmotic, oxidative and acid stress, as well as influenced biofilm formation.
• To examine the impact of deleting the nine cryptic prophages on specific aspects of E. coli physiology, we used phenotype microarrays (PMs) so that 1,240 different metabolic conditions could be rapidly assayed in a high-throughput manner¹³
• six quinolone antibiotics (four shown in Fig. 3a and six in Supplementary Table S1) dramatically inhibited the growth of Δ9
• The fold changes indicate the relative difference in the average slope in the growth curves multiplied by the area under the curves, which is indicative of cell respiration

  • what?
• Powers of 10 indicate the amount of dilution

  • don't understand.

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• • Conventional wisdom tells us that the genes essential to our survival are the ones that are most ancient and conserved over evolutionary time—but that notion was turned upside down this week by a study of fruit flies revealing that about one third of all genes are essential, regardless of when they incorporate themselves into the genome.
    
    Sidi Chen and colleagues compared the genomes of 12 closely related Drosophila species and identified 195 young protein-coding genes that had worked their way into the fruit flies' genomes somewhere between three and 35 million years ago.
    
    The researchers found that a full third of these evolutionarily new genes had already become essential for the flies to live.
    
    According to Chen and colleagues, deleting these genes from the Drosophila genome led to diverse cellular and developmental defects, such as organ formation and patterning defects. Flies in their pupal and larval stages appeared to be especially sensitive to losing these genes, as death most often occurred during those stages. It now seems that the same proportion of new genes compared to old genes is essential for our survival, the researchers say. Their discovery implies that new genes evolve essential functions frequently and rapidly in order to participate in an organism’s development.

• After induction of Dicer1 gene deletion in adult mouse forebrain, we observed a progressive loss of a whole set of brain-specific miRNAs
• we observed an enhancement of memory strength of mutant mice 12 weeks after the Dicer1 gene mutation, before the onset of neurodegenerative process. In acute brain slices, immediately after high-frequency stimulation of the Schaffer collaterals, the efficacy at CA3-to-CA1 synapses was higher in mutant than in control mice, whereas long-term potentiation was comparable between genotypes. This phenotype was reflected at the subcellular and molecular level by the elongated filopodia-like shaped dendritic spines and an increased translation of synaptic plasticity-related proteins, such as BDNF and MMP-9 in mutant animals.

• Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued  genetic change.
• We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog.
• Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes.
• This conservation  is enabled by concomitant changes in the cis-regulatory motifs upstream of each gene.

  • changes in cis motifs in each gene!
• Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another.

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• intercalation of a regulatory circuit that allows both cell type and nutrient levels to control mating.
• S. cerevisiae and C. albicans accomplish this through the direct binding of hsg promoters by a heteromeric repressor, termed a1/alpha2, encoded uniquely in non-mating diploid cells. However, K. lactis has added an interesting wrinkle to this circuit; in this species, the a1/alpha2 repressor does not act directly at the hsg promoters but, rather, shuts off a target gene encoding a transcriptional regulator termed Rme1 that the hsgs need for expression

• Our results establish that a single QTL can act through a confluence of multiple molecular mechanisms and that sequence variation in regions flanking experimentally validated functional elements can have significant quantitative effects on transcriptional activity and phenotype.

• Early cell-lineage decisions during embryonic development differ between mice and cows. This finding calls for a re-examination of developmental variations across mammals