GenomeViz: visualizing microbial genomes

Background

An increasing number of microbial genomes are being sequenced and deposited in public databases. In addition, several closely related strains are also being sequenced in order to understand the genetic basis of diversity and mechanisms that lead to the acquisition of new genetic traits. These exercises have necessitated the requirement for visualizing microbial genomes and performing genome comparisons on a finer scale. We have developed GenomeViz to enable rapid visualization and subsequent comparisons of several microbial genomes in an interactive environment.

Results

Here we describe a program that allows visualization of both qualitative and quantitative information from complete and partially sequenced microbial genomes. Using GenomeViz, data deriving from studies on genomic islands, gene/protein classifications, GC content, GC skew, whole genome alignments, microarrays and proteomics may be plotted. Several genomes can be visualized interactively at the same time from a comparative genomic perspective and publication quality circular genome plots can be created.

Conclusions

GenomeViz should allow researchers to perform visualization and comparative analysis of up to eight different microbial genomes simultaneously.

     

Borrelia genomes in the year 2000

All analyzed members of the spirochete genus Borrelia contain a linear chromosome about 910 kbp long. The complete sequence of the B. burgdorferi B31 genome predicts that its chromosome carries essentially all of this organism's housekeeping genes. In accordance with these bacterial species' obligatory parasitic lifestyle, its genes encode enzymes that are capable of only a minimal metabolism, in which all nucleotides, amino acids, fatty acids and enzyme cofactors must be scavenged from the host. In addition to the chromosome, all Borrelia isolates examined carry multiple linear and circular plasmids with lengths between 5 and 200 kbp. The plasmids, which account for over 600 kbp in isolate B31, carry very few genes with homology to genes outside of the Borrelia genus. But they do carry numerous predicted lipoprotein genes, many of which are have been shown to be or are expected to be outer surface proteins. Ten of the linear plasmids have strikingly low protein coding potential for bacterial DNA. These plasmids have enjoyed numerous past duplicative rearrangements, which have resulted in the presence of a substantial fraction of the DNA that appears to be currently undergoing mutational decay, presumably because it is no longer under selection for function.     

Aldehyde dehydrogenase gene superfamily: the 2000 update

Aldehyde dehydrogenase (ALDH) superfamily represents a group of NAD(P)⁺-dependent enzymes that catalyze the oxidation of a wide spectrum of endogenous and exogenous aldehydes. With the advent of megabase genome sequencing, the ALDH superfamily is expanding rapidly on many fronts. As expected, ALDH genes are found in virtually all genomes analyzed to date, indicating the importance of these enzymes in biological functions. Complete genome sequences of various species have revealed additional ALDH genes. As of July 2000, the ALDH superfamily consists of 331 distinct genes, of which eight are found in archaea, 165 in eubacteria, and 158 in eukaryota. The number of ALDH genes in some species with their genomes completely sequenced and annotated, Escherichia coli and Caenorhabditis elegans, ranges from 10 to 17. In the human genome, 17 functional genes and three pseudogenes have been identified to date. Divergent evolution, based on multiple alignment analysis of 86 eukaryotic ALDH amino-acid sequences, was the basis of the standardized ALDH gene nomenclature system (Pharmacogenetics 9: 421–434, 1999). Thus far, the eukaryotic ALDHs comprise 20 gene families. A complete list of all ALDH sequences known to date is presented here along with the evolution analysis of the eukaryotic ALDHs.     

Aldehyde dehydrogenase gene superfamily: the 2000 update

Aldehyde dehydrogenase (ALDH) superfamily represents a group of NAD(P)(+)-dependent enzymes that catalyze the oxidation of a wide spectrum of endogenous and exogenous aldehydes. With the advent of megabase genome sequencing, the ALDH superfamily is expanding rapidly on many fronts. As expected, ALDH genes are found in virtually all genomes analyzed to date, indicating the importance of these enzymes in biological functions. Complete genome sequences of various species have revealed additional ALDH genes. As of July 2000, the ALDH superfamily consists of 331 distinct genes, of which eight are found in archaea, 165 in eubacteria, and 158 in eukaryota. The number of ALDH genes in some species with their genomes completely sequenced and annotated, Escherichia coli and Caenorhabditis elegans, ranges from 10 to 17. In the human genome, 17 functional genes and three pseudogenes have been identified to date. Divergent evolution, based on multiple alignment analysis of 86 eukaryotic ALDH amino-acid sequences, was the basis of the standardized ALDH gene nomenclature system (Pharmacogenetics 9: 421-434, 1999). Thus far, the eukaryotic ALDHs comprise 20 gene families. A complete list of all ALDH sequences known to date is presented here along with the evolution analysis of the eukaryotic ALDHs.     

Proteomics-based expression library screening (PELS): a novel method for rapidly defining microbial immunoproteomes

Current methodologies for global identification of microbial proteins that elicit host humoral immune responses have several limitations and are not ideally suited for use in the postgenomic era. Here we describe a novel application of proteomics, proteomics-based expression library screening, to rapidly define microbial immunoproteomes. Proteomics-based expression library screening is broadly applicable to any cultivable, sequenced pathogen eliciting host antibody responses and hence is ideal for rapidly mining microbial proteomes for targets with diagnostic, prophylactic, and therapeutic potential. In this report, we demonstrate "proof-of-principle" by identifying 207 proteins of the Escherichia coli O157:H7 immunome in bovine reservoirs in only 3 weeks.     

MITOP, the mitochondrial proteome database: 2000 update

MITOP (http://www.mips.biochem.mpg.de/proj/medgen/mitop/) is a comprehensive database for genetic and functional information on both nuclear- and mitochondrial-encoded proteins and their genes. The five species files--Saccharomyces cerevisiae, Mus musculus, Caenorhabditis elegans, Neurospora crassa and Homo sapiens--include annotated data derived from a variety of online resources and the literature. A wide spectrum of search facilities is given in the overlapping sections 'Gene catalogues', 'Protein catalogues', 'Homologies', 'Pathways and metabolism' and 'Human disease catalogue' including extensive references and hyperlinks to other databases. Central features are the results of various homology searches, which should facilitate the investigations into interspecies relationships. Precomputed FASTA searches using all the MITOP yeast protein entries and a list of the best human EST hits with graphical cluster alignments related to the yeast reference sequence are presented. The orthologue tables with cross-listings to all the protein entries for each species in MITOP have been expanded by adding the genomes of Rickettsia prowazeckii and Escherichia coli. To find new mitochondrial proteins the complete yeast genome has been analyzed using the MITOPROT program which identifies mitochondrial targeting sequences. The 'Human disease catalogue' contains tables with a total of 110 human diseases related to mitochondrial protein abnormalities, sorted by clinical criteria and age of onset. MITOP should contribute to the systematic genetic characterization of the mitochondrial proteome in relation to human disease.     

Genomic Encyclopedia of Type Strains,Phase I: The one thousand microbial genomes (KMG-I) project

The Genomic Encyclopedia of Bacteria and Archaea (GEBA) project was launched by the JGI in 2007 as a pilot project with the objective of sequencing 250 bacterial and archaeal genomes. The two major goals of that project were (a) to test the hypothesis that there are many benefits to the use the phylogenetic diversity of organisms in the tree of life as a primary criterion for generating their genome sequence and (b) to develop the necessary framework, technology and organization for large-scale sequencing of microbial isolate genomes. While the GEBA pilot project has not yet been entirely completed, both of the original goals have already been successfully accomplished, leading the way for the next phase of the project.Here we propose taking the GEBA project to the next level, by generating high quality draft genomes for 1,000 bacterial and archaeal strains. This represents a combined 16-fold increase in both scale and speed as compared to the GEBA pilot project (250 isolate genomes in 4+ years). We will follow a similar approach for organism selection and sequencing prioritization as was done for the GEBA pilot project (i.e. phylogenetic novelty, availability and growth of cultures of type strains and DNA extraction capability), focusing on type strains as this ensures reproducibility of our results and provides the strongest linkage between genome sequences and other knowledge about each strain. In turn, this project will constitute a pilot phase of a larger effort that will target the genome sequences of all available type strains of the Bacteria and Archaea.     

Evolution of microbial genomes: sequence acquisition and loss

We present models describing the acquisition and deletion of novel sequences in populations of microorganisms. We infer that most novel sequences are neutral. Thus, sequence duplications and gene transfer between organisms sharing the same environment are rarely expected to generate adaptive functions. Two classes of models are considered: (1) a homogeneous population with constant size, and (2) an island model in which the population is subdivided into patches that are in contact through slow migration. Distributions of gene frequencies are derived in a Moran model with overlapping generations. We find that novel, neutral or near-neutral coding sequences in microorganisms will not be fixed globally because they offer large target sizes for mutations and because the populations are so large. At most, such genes may have a transient presence in only a small fraction of the population. Consequently, a microbial population is expected to have a very large diversity of transient neutral gene content. Only sequences that are under strong selection, globally or in individual patches, can be expected to persist. We suggest that genome size is maintained in microorganisms by a quasi-steady state mechanism in which random fluctuations in the effective acquisition and deletion rates result in genome sizes that vary from patch to patch. We assign the genomic identity of a global population to those genes that are required for the participation of patches in the genetic sweeps that maintain the genomic coherence of the population. In contrast, we stress the influence of sequence loss on the isolation and the divergence (speciation) of novel patches from a global population.     

Genome Information Broker (GIB): data retrieval and comparative analysis system for completed microbial genomes and more

Genome Information Broker (GIB) is a powerful tool for the study of comparative genomics. GIB allows users to retrieve and display partial and/or whole genome sequences together with the relevant biological annotation. GIB has accumulated all the completed microbial genome and has recently been expanded to include Arabidopsis thaliana genome data from DDBJ/EMBL/GenBank. In the near future, hundreds of genome sequences will be determined. In order to handle such huge data, we have enhanced the GIB architecture by using XML, CORBA and distributed RDBs. We introduce the new GIB here. GIB is freely accessible at http://gib.genes.nig.ac.jp/.     

Streamlining genomes: toward the generation of simplified and stabilized microbial systems

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Highlights? Top-down and bottom-up approaches to genome streamlining. ? Computational support for constructing and refactoring streamlined genomes. ? From genome engineering to metabolic reprogramming. ? Perspectives in applied genome engineering.     

Microbial fuel cell (MFC) power performance improvement through enhanced microbial electrogenicity

Within the past 5?years, tremendous advances have been made to maximize the performance of microbial fuel cells (MFCs) for both “clean” bioenergy production and bioremediation. Most research efforts have focused on parameters including (i) optimizing reactor configuration, (ii) electrode construction, (iii) addition of redox-active, electron donating mediators, (iv) biofilm acclimation and feed nutrient adjustment, as well as (v) other parameters that contribute to enhanced MFC performance. To date, tremendous advances have been made, but further improvements are needed for MFCs to be economically practical. In this review, the diversity of electrogenic microorganisms and microbial community changes in mixed cultures are discussed. More importantly, different approaches including chemical/genetic modifications and gene regulation of exoelectrogens, synthetic biology approaches and bacterial community cooperation are reviewed. Advances in recent years in metagenomics and microbiomes have allowed researchers to improve bacterial electrogenicity of robust biofilms in MFCs using novel, unconventional approaches. Taken together, this review provides some important and timely information to researchers who are examining additional means to enhance power production of MFCs.     

On the nature of gene innovation: duplication patterns in microbial genomes

Gene duplication is considered a major force in gene family expansion and gene innovation. As gene copies assume novel functions, they must avoid periods of neutrality or be deleted from the genome. Current opinions state that copies avoid neutrality through gene dosage effects. These copies are therefore selected from an early stage. This study concentrates on the flow of copies from recent duplication to gene innovation. We have studied 21 microbial genomes using amino acid divergence to describe paralog evolution in the long-term perspective. Five of these were studied in closer detail using nucleotide divergence for a shorter perspective. It was found that rates of duplication and deletion are high, with only a small fraction of duplications retained and apparently selected. This leads to a steady accumulation of paralogs, which seems to be of a similar magnitude in most of the genomes. Furthermore, it is found that genes of high expression level, as measured by their codon bias, are strongly underrepresented among the most recent duplications. Based on these and other observations, it is suggested that gene innovation is driven by amplification of weak, ancillary functions rather than strong, established functions.     

Comparison of mono-rhamnolipids and di-rhamnolipids on microbial enhanced oil recovery (MEOR) applications

Rhamnolipids (RMLs) have more effectiveness for specific uses according to their homologue proportions. Thus, the novelty of this work was to compare mono-RMLs and di-RMLs physicochemical properties on microbial enhanced oil recovery (MEOR) applications. For this, RML produced by three strains of Pseudomonas aeruginosa containing different homologues proportion were used: a mainly mono-RMLs producer (mono-RMLs); a mainly di-RMLs producer (di-RMLs), and the other one that produces relatively balanced amounts of mono-RML and di-RML homologues (mono/di-RML). For mono-RML, the most abundant molecules were Rha-C₁₀C₁₀ (m/z 503.3), for di-RML were RhaRha-C₁₀C₁₀ (m/z 649.4) and for Mono/di-RML were Rha-C₁₀C₁₀ (m/z 503.3) and RhaRha-C₁₀C₁₀ (m/z 649.4). All RMLs types presented robustness under high temperature and variation of salinity and pH, and high ability for oil displacement, foam stability, wettability reversal and were classified as safe for environment according to the European Union Directive No. 67/548/EEC. For all these properties, it was observed a highlight for mono-RML. Mono-RML presented the lowest surface tension (26.40 mN/m), interfacial tension (1.14 mN/m), and critical micellar concentration (CMC 27.04 mg/L), the highest emulsification index (EI₂₄ 100%) and the best wettability reversal (100% with 25 ppm). In addition, mono-RML showed the best acute toxicity value (454 mg/L), making its application potential even more attractive. Based on the results, it was concluded that all RMLs homologues studied have potential for MEOR applications. However, results showed that mono-RML stood out and have the best mechanism of oil incorporation in micelles due their most effective surface-active physicochemical features.     

Sonobioreactors: using ultrasound for enhanced microbial productivity

Enhanced metabolic productivity of microbial, plant and animal cells in bioreactors can greatly improve the economics of biotechnology processes. Ultrasound is one method of intensifying the performance of live biocatalysts. Ultrasonication is generally associated with damage to cells but evidence is emerging for beneficial effects of controlled sonication on conversions catalyzed by live cells. This review focuses on the productivity enhancing effects of ultrasound on live biological systems and the design considerations for sonobioreactors required for ultrasound-enhanced biocatalysis.     

GWFASTA: server for FASTA search in eukaryotic and microbial genomes

Similarity searches are a powerful method for solving important biological problems such as database scanning, evolutionary studies, gene prediction, and protein structure prediction. FASTA is a widely used sequence comparison tool for rapid database scanning. Here we describe the GWFASTA server that was developed to assist the FASTA user in similarity searches against partially and/or completely sequenced genomes. GWFASTA consists of more than 60 microbial genomes, eight eukaryote genomes, and proteomes of annotatedgenomes. Infact, it provides the maximum number of databases for similarity searching from a single platform. GWFASTA allows the submission of more than one sequence as a single query for a FASTA search. It also provides integrated post-processing of FASTA output, including compositional analysis of proteins, multiple sequences alignment, and phylogenetic analysis. Furthermore, it summarizes the search results organism-wise for prokaryotes and chromosome-wise for eukaryotes. Thus, the integration of different tools for sequence analyses makes GWFASTA a powerful toolfor biologists.     

Charcot-Marie-Tooth (CMT) disease: an update

Charcot-Marie-Tooth (CMT) is the generic name given to a group of genetic disorders characterized by a relatively isolated dysfunction of peripheral nerves, with combined motor and sensory impairment. These CMT syndromes are the most frequent genetically-determined peripheral neuropathies, with a global prevalence between 4.7 and 36/100,000. Their clinical phenotype is predominantly motor, with a grossly symmetrical distal amyotrophy involving both lower and upper limbs. Mode of inheritance is variable: autosomal dominant, autosomal recessive or X-linked. Apparently sporadic forms can be a difficult diagnosis and they must be considered in all patients with a chronic polyneuropathy which is not clearly of acquired origin. During the last two decades, the identification of more than 25 genes mutated in CMT syndromes has complicated the classification of these disorders. Knowledge of the function of some of these genes has improved our understanding of the pathogenesis of myelinic or axonal dysfunction in CMT, but for some others their function remains elusive or unknown.     

Delta-sleep-inducing peptide (DSIP): An update

The isolation and characterization of delta-sleep-inducing peptide (DSIP) achieved from 1963 to 1977 were reviewed in 1984. The first reports describing sleep as well as extra-sleep effects of DSIP also were included in that work. Only two years later, much additional literature concerning DSIP has accumulated. Besides further sleep-inducing and/or-supporting effects of DSIP in animals, considerable work has been carried out to evaluate the potential use of the peptide for therapeutic purposes such as treatment of insomnia, pain, and withdrawal. Immunohistochemical as well as radioimmunochemical studies provided further insights into the natural occurrence of the nonapeptide and the distribution of DSIP-like material in the body, suggesting possible relations of the peptide to certain diseases. Various physiological functions of DSIP and a possible mechanism of action involving the modulation of adrenergic transmission remain to be established.