Hox and HOM: Homologous gene clusters in insects and vertebrates

Cell ◽  
1989 ◽  
Vol 57 (3) ◽  
pp. 347-349 ◽  
Author(s):  
Michael Akam
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emmanuel Matabaro ◽  
Hannelore Kaspar ◽  
Paul Dahlin ◽  
Daniel L. V. Bader ◽  
Claudia E. Murar ◽  
...  

AbstractBackbone N-methylation and macrocyclization improve the pharmacological properties of peptides by enhancing their proteolytic stability, membrane permeability and target selectivity. Borosins are backbone N-methylated peptide macrocycles derived from a precursor protein which contains a peptide α-N-methyltransferase domain autocatalytically modifying the core peptide located at its C-terminus. Founding members of borosins are the omphalotins from the mushroom Omphalotus olearius (omphalotins A-I) with nine out of 12 L-amino acids being backbone N-methylated. The omphalotin biosynthetic gene cluster codes for the precursor protein OphMA, the protease prolyloligopeptidase OphP and other proteins that are likely to be involved in other post-translational modifications of the peptide. Mining of available fungal genome sequences revealed the existence of highly homologous gene clusters in the basidiomycetes Lentinula edodes and Dendrothele bispora. The respective borosins, referred to as lentinulins and dendrothelins are naturally produced by L. edodes and D. bispora as shown by analysis of respective mycelial extracts. We produced all three homologous peptide natural products by coexpression of OphMA hybrid proteins and OphP in the yeast Pichia pastoris. The recombinant peptides differ in their nematotoxic activity against the plant pathogen Meloidogyne incognita. Our findings pave the way for the production of borosin peptide natural products and their potential application as novel biopharmaceuticals and biopesticides.


2004 ◽  
Vol 186 (9) ◽  
pp. 2880-2890 ◽  
Author(s):  
Isabelle Vallet ◽  
Stephen P. Diggle ◽  
Rachael E. Stacey ◽  
Miguel Cámara ◽  
Isabelle Ventre ◽  
...  

ABSTRACT Pseudomonas aeruginosa is an opportunistic bacterial pathogen which poses a major threat to long-term-hospitalized patients and individuals with cystic fibrosis. The capacity of P. aeruginosa to form biofilms is an important requirement for chronic colonization of human tissues and for persistence in implanted medical devices. Various stages of biofilm formation by this organism are mediated by extracellular appendages, such as type IV pili and flagella. Recently, we identified three P. aeruginosa gene clusters that were termed cup (chaperone-usher pathway) based on their sequence relatedness to the chaperone-usher fimbrial assembly pathway in other bacteria. The cupA gene cluster, but not the cupB or cupC cluster, is required for biofilm formation on abiotic surfaces. In this study, we identified a gene (mvaT) encoding a negative regulator of cupA expression. Such regulatory control was confirmed by several approaches, including lacZ transcriptional fusions, Northern blotting, and transcriptional profiling using DNA microarrays. MvaT also represses the expression of the cupB and cupC genes, although the extent of the regulatory effect is not as pronounced as with cupA. Consistent with this finding, mvaT mutants exhibit enhanced biofilm formation. Although the P. aeruginosa genome contains a highly homologous gene, mvaU, the repression of cupA genes is MvaT specific. Thus, MvaT appears to be an important regulatory component within a complex network that controls biofilm formation and maturation in P. aeruginosa.


Microbiology ◽  
2003 ◽  
Vol 149 (9) ◽  
pp. 2545-2556 ◽  
Author(s):  
Doreen Hoffmann ◽  
Sabine Kleinsteuber ◽  
Roland H. Müller ◽  
Wolfgang Babel

The bacterial strain Delftia acidovorans P4a, isolated from an extreme environment (heavily contaminated with organochlorines, highly alkaline conditions in an aqueous environment), was found to mineralize 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxyacetic acid under alkaline conditions. Screening a genomic DNA library of the alkalitolerant strain for 2,4-D genes revealed the presence of the two 2,4-D gene clusters tfdCDEF and tfdC II E II BKA, tfdR genes being located in the vicinity of each tfd gene cluster. The results showed that the putative genes of the complete 2,4-D degradation pathway are organized in a single genomic unit. Sequence similarities to homologous gene clusters indicate that the individual tfd elements of strain P4a do not share a common origin, but were brought together by recombination events. The entire region is flanked by insertion elements of the IS1071 and IS1380 families, forming a transposon-like structure of about 30 kb, of which 28·4 kb were analysed. This element was shown to be located on the bacterial chromosome. The present study provides the first reported case of a chromosomally located catabolic transposon which carries the genes for the complete 2,4-D degradation pathway.


2010 ◽  
Vol 77 (4) ◽  
pp. 1214-1220 ◽  
Author(s):  
Toshiki Furuya ◽  
Satomi Hirose ◽  
Hisashi Osanai ◽  
Hisashi Semba ◽  
Kuniki Kino

ABSTRACTMycobacterium goodiistrain 12523 is an actinomycete that is able to oxidize phenol regioselectively at theparaposition to produce hydroquinone. In this study, we investigated the genes responsible for this unique regioselective oxidation. On the basis of the fact that the oxidation activity ofM. goodiistrain 12523 toward phenol is induced in the presence of acetone, we first identified acetone-induced proteins in this microorganism by two-dimensional electrophoretic analysis. The N-terminal amino acid sequence of one of these acetone-induced proteins shares 100% identity with that of the protein encoded by the open reading frame Msmeg_1971 inMycobacterium smegmatisstrain mc2155, whose genome sequence has been determined. Since Msmeg_1971, Msmeg_1972, Msmeg_1973, and Msmeg_1974 constitute a putative binuclear iron monooxygenase gene cluster, we cloned this gene cluster ofM. smegmatisstrain mc2155 and its homologous gene cluster found inM. goodiistrain 12523. Sequence analysis of these binuclear iron monooxygenase gene clusters revealed the presence of four genes designatedmimABCD, which encode an oxygenase large subunit, a reductase, an oxygenase small subunit, and a coupling protein, respectively. When themimAgene (Msmeg_1971) ofM. smegmatisstrain mc2155, which was also found to be able to oxidize phenol to hydroquinone, was deleted, this mutant lost the oxidation ability. This ability was restored by introduction of themimAgene ofM. smegmatisstrain mc2155 or ofM. goodiistrain 12523 into this mutant. Interestingly, we found that these gene clusters also play essential roles in propane and acetone metabolism in these mycobacteria.


2020 ◽  
Vol 36 (12) ◽  
pp. 3871-3873 ◽  
Author(s):  
Xiangyang Li ◽  
Fang Chen ◽  
Yunpeng Chen

Abstract Motivation Comparing the organization of gene, gene clusters and their flanking genomic contexts is of critical importance to the determination of gene function and evolutionary basis of microbial traits. Currently, user-friendly and flexible tools enabling to visualize and compare genomic contexts for numerous genomes are still missing. Results We here present Gcluster, a stand-alone Perl tool that allows researchers to customize and create high-quality linear maps of the genomic region around the genes of interest across large numbers of completed and draft genomes. Importantly, Gcluster integrates homologous gene analysis, in the form of a built-in orthoMCL, and mapping genomes onto a given phylogeny to provide superior comparison of gene contexts. Availability and implementation Gcluster is written in Perl and released under GPLv3. The source code is freely available at https://github.com/Xiangyang1984/Gcluster and http://www.microbialgenomic.com/Gcluster_tool.html. Gcluster can also be installed through conda: ‘conda install -c bioconda gcluster’. Supplementary information Supplementary data are available at Bioinformatics online.


2021 ◽  
Author(s):  
Alexander G McFarland ◽  
Nolan W Kennedy ◽  
Carolyn E Mills ◽  
Danielle Tullman-Ercek ◽  
Curtis Huttenhower ◽  
...  

Motivation: Identifying gene clusters of interest in phylogenetically proximate and distant taxa can help to infer phenotypes of interest. Conserved gene clusters may differ by only a few genes, which can be biologically meaningful, such as the formation of pseudogenes or insertions interrupting regulation. These qualities may allow for unsupervised clustering of similar gene clusters into bins that provide a population-level understanding of the genetic variation in similar gene clusters. Results: We developed GeneGrouper, a command-line tool that uses a density-based clustering method to group gene clusters into bins. GeneGrouper demonstrated high recall and precision in benchmarks for the detection of the 23-gene Salmonella enterica LT2 Pdu gene cluster and four-gene Pseudomonas aeruginosa PAO1 Mex gene cluster in 435 genomes containing mixed taxa. In a subsequent application investigating the diversity and impact of gene complete and incomplete LT2 Pdu gene clusters in 1130 S. enterica genomes, GeneGrouper identified a novel, frequently occurring pduN pseudogene. When replicated in vivo, disruption of pduN with a frameshift mutation negatively impacted microcompartment formation. We next demonstrated the versatility of GeneGrouper by clustering both distant homologous gene clusters and variable gene clusters found in integrative and conjugative elements.


2020 ◽  
Author(s):  
Dina Kačar ◽  
Librada M Cañedo ◽  
Pilar Rodríguez ◽  
Elena Gonzalez ◽  
Beatriz Galán ◽  
...  

AbstractGlutaramide-containing polyketides are known as potent antitumoral and antimetastatic agents. However, the associated gene clusters have only been identified and studied in a few Streptomyces producers and sole Burkholderia gladioli symbiont. The new glutaramide-family polyketides, denominated sesbanimides D, E and F along with the previously known sesbanimide A and C, were isolated from two marine alphaproteobacteria Stappia indica PHM037 and Labrenzia aggregata PHM038. Structures of the isolated compounds were elucidated based on 1D and 2D homo and heteronuclear NMR analyses and ESI-MS spectrometry. All compounds exhibited strong antitumor activity in lung, breast and colorectal cancer cell lines. Subsequent whole genome sequencing and genome mining revealed the presence of the trans-AT PKS gene cluster responsible for the sesbanimide biosynthesis, described as sbn cluster, and the sesbanimide modular assembly is proposed. Interestingly, numerous homologous orphan gene clusters were localized in distantly related bacteria and used as comparative genomic assets for a more global characterization of sbn like-clusters. Strikingly, the modular architecture of downstream mixed type PKS/NRPS, SbnQ, revealed high similarity to PedH in pederin and Lab13 in labrenzin gene clusters, although those clusters are responsible for the production of structurally completely different molecules. The unexpected presence of SbnQ homologs in unrelated polyketide gene clusters across phylogenetically distant bacteria, raises intriguing questions about the evolutionary relationship between glutaramide-like and pederin-like pathways, as well as the functionality of their synthetic products.SignificanceGlutaramide-containing polyketides are still a largely understudied group of polyketides, produced mainly by the genera Streptomyces, with a great potential for antitumor drug production. Here, we describe genomes of two cultivable marine bacteria, Stappia indica PHM037 and Labrenzia aggregata PHM038, producers of the cytotoxic glutaramide-family polyketides sesbanimide A and C with chemical elucidation of newly identified analogs D, E and F. Genome mining revealed trans-AT PKS gene cluster responsible for sesbanimide biosynthesis. Although there are numerous homologous gene clusters present in remarkably different bacteria, this is the first time that the biosynthesis product has been reported. The comparative genome analysis reveals stunning, cryptic evolutionary relationship between sesbanimides, glutaramides from Streptomyces spp. and the pederin-family gene clusters.


Author(s):  
Cameron L.M. Gilchrist ◽  
Thomas J. Booth ◽  
Yit-Heng Chooi

AbstractGenes involved in coordinated biological pathways, including metabolism, drug resistance and virulence, are often collocalised as gene clusters. Identifying homologous gene clusters aids in the study of their function and evolution, however existing tools are limited to searching local sequence databases. Tools for remotely searching public databases are necessary to keep pace with the rapid growth of online genomic data. Here, we present cblaster, a Python based tool to rapidly detect collocated genes in local and remote databases. cblaster is easy to use, offering both a command line and a user-friendly graphical user interface (GUI). It generates outputs that enable intuitive visualisations of large datasets, and can be readily incorporated into larger bioinformatic pipelines. cblaster is a significant update to the comparative genomics toolbox. cblaster source code and documentation is freely available from GitHub under the MIT license (github.com/gamcil/cblaster).


2021 ◽  
Author(s):  
Robert W. Murdoch ◽  
Gao Chen ◽  
Fadime Kara Murdoch ◽  
E. Erin Mack ◽  
Manuel I. Villalobos Solis ◽  
...  

AbstractAnthropogenic activities and natural processes release dichloromethane (DCM), a toxic chemical with substantial ozone-depleting capacity. Specialized anaerobic bacteria metabolize DCM; however, the genetic basis for this process has remained elusive. Comparative genomics of the three known anaerobic DCM-degrading bacterial species revealed a homologous gene cluster, designated the methylene chloride catabolism (mec) gene cassette, comprising eight to ten genes with predicted 79.6 – 99.7% amino acid identity. Functional annotation identified genes encoding a corrinoid-dependent methyltransferase system, and shotgun proteomics applied to two DCM-catabolizing cultures revealed high expression of proteins encoded on the mec gene cluster during anaerobic growth with DCM. In a DCM-contaminated groundwater plume, the abundance of mec genes strongly correlated with DCM concentrations (R2 = 0.71 – 0.85) indicating their value as process-specific bioremediation biomarkers. mec gene clusters were identified in metagenomes representing peat bogs, the deep subsurface, and marine ecosystems including oxygen minimum zones (OMZs), suggesting DCM turnover in diverse habitats. The broad distribution of anaerobic DCM catabolic potential suggests a relevant control function for emissions to the atmosphere, and a role for DCM as a microbial energy source in critical zone environments. The findings imply that the global DCM flux might be far greater than emission measurements suggest.ImportanceDichloromethane (DCM) is an increasing threat to stratospheric ozone with both anthropogenic and natural emission sources. Anaerobic bacterial metabolism of DCM has not yet been taken into consideration as a factor in the global DCM cycle. The discovery of the mec gene cassette associated with anaerobic bacterial DCM metabolism and its widespread distribution in environmental systems highlight a strong attenuation potential for DCM. Knowledge of the mec cassette offers new opportunities to delineate DCM sources, enables more robust estimates of DCM fluxes, supports refined DCM emission modeling and simulation of the stratospheric ozone layer, reveals a novel, ubiquitous C1 carbon metabolic system, and provides prognostic and diagnostic tools supporting bioremediation of groundwater aquifers impacted by DCM.


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