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Signal Transduction and Targeted Therapy Oct 2022
Topics: Operon; Transcription, Genetic
PubMed: 36243717
DOI: 10.1038/s41392-022-01195-5 -
PLoS Computational Biology Apr 2020In bacteria functionally related genes comprising metabolic pathways and protein complexes are frequently encoded in operons and are widely conserved across...
In bacteria functionally related genes comprising metabolic pathways and protein complexes are frequently encoded in operons and are widely conserved across phylogenetically diverse species. The evolution of these operon-encoded processes is affected by diverse mechanisms such as gene duplication, loss, rearrangement, and horizontal transfer. These mechanisms can result in functional diversification, increasing the potential evolution of novel biological pathways, and enabling pre-existing pathways to adapt to the requirements of particular environments. Despite the fundamental importance that these mechanisms play in bacterial environmental adaptation, a systematic approach for studying the evolution of operon organization is lacking. Herein, we present a novel method to study the evolution of operons based on phylogenetic clustering of operon-encoded protein families and genomic-proximity network visualizations of operon architectures. We applied this approach to study the evolution of the synthase dependent exopolysaccharide (EPS) biosynthetic systems: cellulose, acetylated cellulose, poly-β-1,6-N-acetyl-D-glucosamine (PNAG), Pel, and alginate. These polymers have important roles in biofilm formation, antibiotic tolerance, and as virulence factors in opportunistic pathogens. Our approach revealed the complex evolutionary landscape of EPS machineries, and enabled operons to be classified into evolutionarily distinct lineages. Cellulose operons show phyla-specific operon lineages resulting from gene loss, rearrangement, and the acquisition of accessory loci, and the occurrence of whole-operon duplications arising through horizonal gene transfer. Our evolution-based classification also distinguishes between PNAG production from Gram-negative and Gram-positive bacteria on the basis of structural and functional evolution of the acetylation modification domains shared by PgaB and IcaB loci, respectively. We also predict several pel-like operon lineages in Gram-positive bacteria and demonstrate in our companion paper (Whitfield et al PLoS Pathogens, in press) that Bacillus cereus produces a Pel-dependent biofilm that is regulated by cyclic-3',5'-dimeric guanosine monophosphate (c-di-GMP).
Topics: Bacterial Proteins; Biofilms; Biological Evolution; Computational Biology; Evolution, Molecular; Gene Duplication; Operon; Phylogeny; Virulence Factors
PubMed: 32236097
DOI: 10.1371/journal.pcbi.1007721 -
Current Opinion in Structural Biology Feb 2017Most proteins assemble into complexes, which are involved in almost all cellular processes. Thus it is crucial for cell viability that mechanisms for correct assembly... (Review)
Review
Most proteins assemble into complexes, which are involved in almost all cellular processes. Thus it is crucial for cell viability that mechanisms for correct assembly exist. The timing of assembly plays a key role in determining the fate of the protein: if the protein is allowed to diffuse into the crowded cellular milieu, it runs the risk of forming non-specific interactions, potentially leading to aggregation or other deleterious outcomes. It is therefore expected that strong regulatory mechanisms should exist to ensure efficient assembly. In this review we discuss the cotranslational assembly of protein complexes and discuss how it occurs, ways in which it is regulated, potential disadvantages of cotranslational interactions between proteins and the implications for the inheritance of dominant-negative genetic disorders.
Topics: Animals; Disease; Evolution, Molecular; Humans; Operon; Protein Biosynthesis; Proteins
PubMed: 27969102
DOI: 10.1016/j.sbi.2016.11.023 -
Applied and Environmental Microbiology Jun 2023In our previous study, the phenazine-1-carboxylic acid (PCA) 1,2-dioxygenase gene cluster ( cluster) in Sphingomonas histidinilytica DS-9 was identified to be...
PcaR, a GntR/FadR Family Transcriptional Repressor Controls the Transcription of Phenazine-1-Carboxylic Acid 1,2-Dioxygenase Gene Cluster in Sphingomonas histidinilytica DS-9.
In our previous study, the phenazine-1-carboxylic acid (PCA) 1,2-dioxygenase gene cluster ( cluster) in Sphingomonas histidinilytica DS-9 was identified to be responsible for the conversion of PCA to 1,2-dihydroxyphenazine (Ren Y, Zhang M, Gao S, Zhu Q, et al. 2022. Appl Environ Microbiol 88:e00543-22). However, the regulatory mechanism of the cluster has not been elucidated yet. In this study, the cluster was found to be transcribed as two divergent operons: - (named operon) and -- (named operon). The promoter regions of the two operons were overlapped. PcaR acts as a transcriptional repressor of the cluster, and it belongs to GntR/FadR family transcriptional regulator. Gene disruption of can shorten the lag phase of PCA degradation. The results of electrophoretic mobility shift assay and DNase I footprinting showed that PcaR binds to a 25-bp motif in the - intergenic promoter region to regulate the expression of two operons. The 25-bp motif covers the -10 region of the promoter of operon and the -35 region and -10 region of the promoter of - operon. The TNGT/ANCNA box within the motif was essential for PcaR binding to the two promoters. PCA acted as an effector of PcaR, preventing it from binding to the promoter region and repressing the transcription of the cluster. In addition, PcaR represses its own transcription, and this repression can be relieved by PCA. This study reveals the regulatory mechanism of PCA degradation in strain DS-9, and the identification of PcaR increases the variety of regulatory model of the GntR/FadR-type regulator. Sphingomonas histidinilytica DS-9 is a phenazine-1-carboxylic acid (PCA)-degrading strain. The 1,2-dioxygenase gene cluster ( cluster, encoding dioxygenase PcaA1A2, reductase PcaA3, and ferredoxin PcaA4) is responsible for the initial degradation step of PCA and widely distributed in Sphingomonads, but its regulatory mechanism has not been investigated yet. In this study, a GntR/FadR-type transcriptional regulator PcaR repressing the transcription of cluster and gene was identified and characterized. The binding site of PcaR in - intergenic promoter region contains a TNGT/ANCNA box, which is important for the binding. These findings enhance our understanding of the molecular mechanism of PCA degradation.
Topics: Dioxygenases; Bacterial Proteins; Transcription Factors; Multigene Family; Gene Expression Regulation, Bacterial; Operon
PubMed: 37191535
DOI: 10.1128/aem.02121-22 -
Current Biology : CB Sep 2010
Topics: Biological Evolution; Cooperative Behavior; History, 20th Century; Operon; United States
PubMed: 20833316
DOI: 10.1016/j.cub.2010.06.027 -
Briefings in Bioinformatics Sep 2008For most organisms, computational operon predictions are the only source of genome-wide operon information. Operon prediction methods described in literature are based... (Review)
Review
For most organisms, computational operon predictions are the only source of genome-wide operon information. Operon prediction methods described in literature are based on (a combination of) the following five criteria: (i) intergenic distance, (ii) conserved gene clusters, (iii) functional relation, (iv) sequence elements and (v) experimental evidence. The performance estimates of operon predictions reported in literature cannot directly be compared due to differences in methods and data used in these studies. Here, we survey the current status of operon prediction methods. Based on a comparison of the performance of operon predictions on Escherichia coli and Bacillus subtilis we conclude that there is still room for improvement. We expect that existing and newly generated genomics and transcriptomics data will further improve accuracy of operon prediction methods.
Topics: Algorithms; Base Sequence; Chromosome Mapping; Computer Simulation; Models, Genetic; Molecular Sequence Data; Operon; Sequence Alignment; Sequence Analysis, DNA; Software
PubMed: 18420711
DOI: 10.1093/bib/bbn019 -
Applied Microbiology and Biotechnology Apr 2018The antibiotic pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite that plays an important role in the biocontrol of plant diseases due to its broad-spectrum...
The antibiotic pyrrolnitrin (PRN) is a tryptophan-derived secondary metabolite that plays an important role in the biocontrol of plant diseases due to its broad-spectrum of antimicrobial activities. The PRN biosynthetic gene cluster remains to be characterised in Serratia plymuthica, though it is highly conserved in PRN-producing bacteria. To better understand PRN biosynthesis and its regulation in Serratia, the prnABCD operon from S. plymuthica G3 was cloned, sequenced and expressed in Escherichia coli DH5α. Furthermore, an engineered strain prnind which is a conditional mutant of G3 prnABCD under the control of the Ptac promoter was constructed. This mutant was able to overproduce PRN with isopropylthiogalactoside (IPTG) induction by overexpressing prnABCD, whilst behaving as a conditional mutant of G3 prnABCD in the absence of IPTG. These results confirmed that prnABCD is responsible for PRN biosynthesis in strain G3. Further experiments involving lux-/dsRed-based promoter fusions, combined with site-directed mutagenesis of the putative σ extended -10 region in the prnA promoter, and liquid chromatography-mass spectrometry (LC-MS) analysis extended our previous knowledge about G3, revealing that quorum sensing (QS) regulates PRN biosynthesis through cross talk with RpoS, which may directly activated prnABCD transcription. These findings suggest that PRN in S. plymuthica G3 is produced in a tightly controlled manner, and has diverse functions, such as modulation of cell motility, in addition to antimicrobial activities. Meanwhile, the construction of inducible mutants could be a powerful tool to improve PRN production, beyond its potential use for the investigation of the biological function of PRN.
Topics: Gene Expression Regulation, Bacterial; Mutation; Operon; Pyrrolnitrin; Quorum Sensing; Serratia
PubMed: 29511844
DOI: 10.1007/s00253-018-8857-0 -
Genome Biology and Evolution 2013In prokaryotes, genome size is associated with metabolic versatility, regulatory complexity, effective population size, and horizontal transfer rates. We therefore...
In prokaryotes, genome size is associated with metabolic versatility, regulatory complexity, effective population size, and horizontal transfer rates. We therefore analyzed the covariation of genome size and operon conservation to assess the evolutionary models of operon formation and maintenance. In agreement with previous results, intraoperonic pairs of essential and of highly expressed genes are more conserved. Interestingly, intraoperonic pairs of genes are also more conserved when they encode proteins at similar cell concentrations, suggesting a role of cotranscription in diminishing the cost of waste and shortfall in gene expression. Larger genomes have fewer and smaller operons that are also less conserved. Importantly, lower conservation in larger genomes was observed for all classes of operons in terms of gene expression, essentiality, and balanced protein concentration. We reached very similar conclusions in independent analyses of three major bacterial clades (α- and β-Proteobacteria and Firmicutes). Operon conservation is inversely correlated to the abundance of transcription factors in the genome when controlled for genome size. This suggests a negative association between the complexity of genetic networks and operon conservation. These results show that genome size and/or its proxies are key determinants of the intensity of natural selection for operon organization. Our data fit better the evolutionary models based on the advantage of coregulation than those based on genetic linkage or stochastic gene expression. We suggest that larger genomes with highly complex genetic networks and many transcription factors endure weaker selection for operons than smaller genomes with fewer alternative tools for genetic regulation.
Topics: Escherichia coli; Escherichia coli Proteins; Evolution, Molecular; Genome Size; Operon; Selection, Genetic
PubMed: 24201372
DOI: 10.1093/gbe/evt174 -
Research in Microbiology Sep 2013Many bacterial genes are in operons and the process whereby operons are formed is therefore fundamental. To help elucidate this process, we propose in the Scribbling Pad... (Review)
Review
Many bacterial genes are in operons and the process whereby operons are formed is therefore fundamental. To help elucidate this process, we propose in the Scribbling Pad hypothesis that bacteria have been constantly using plasmids for genetic experimentation and, in particular, for the construction of operons. This hypothesis simultaneously solves the problems of the creation of operons and the way operons are propagated. We cite results in the literature to support the hypothesis and make experimental predictions to test it.
Topics: Bacteria; Models, Genetic; Operon; Plasmids
PubMed: 23587635
DOI: 10.1016/j.resmic.2013.04.003 -
Co-transfer of functionally interdependent genes contributes to genome mosaicism in lambdoid phages.Microbial Genomics Nov 2022Lambdoid (or Lambda-like) phages are a group of related temperate phages that can infect and other gut bacteria. A key characteristic of these phages is their mosaic...
Lambdoid (or Lambda-like) phages are a group of related temperate phages that can infect and other gut bacteria. A key characteristic of these phages is their mosaic genome structure, which served as the basis for the 'modular genome hypothesis'. Accordingly, lambdoid phages evolve by transferring genomic regions, each of which constitutes a functional unit. Nevertheless, it is unknown which genes are preferentially transferred together and what drives such co-transfer events. Here we aim to characterize genome modularity by studying co-transfer of genes among 95 distantly related lambdoid (pro-)phages. Based on gene content, we observed that the genomes cluster into 12 groups, which are characterized by a highly similar gene content within the groups and highly divergent gene content across groups. Highly similar proteins can occur in genomes of different groups, indicating that they have been transferred. About 26 % of homologous protein clusters in the four known operons (i.e. the early left, early right, immunity and late operon) engage in gene transfer, which affects all operons to a similar extent. We identified pairs of genes that are frequently co-transferred and observed that these pairs tend to be near one another on the genome. We find that frequently co-transferred genes are involved in related functions and highlight interesting examples involving structural proteins, the cI repressor and Cro regulator, proteins interacting with DNA, and membrane-interacting proteins. We conclude that epistatic effects, where the functioning of one protein depends on the presence of another, play an important role in the evolution of the modular structure of these genomes.
Topics: Bacteriophages; Mosaicism; Operon
PubMed: 36748576
DOI: 10.1099/mgen.0.000915