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Biomedical subjects

Jan Mrázek

Publications and source records attributed to Jan Mrázek.

11 recordsLinked to original sources

Pattern locator: a new tool for finding local sequence patterns in genomic DNA sequences.

UNLABELLED: We present a new tool for finding local sequence patterns in long DNA sequences. The program, Pattern Locator, uses an intuitive syntax for pattern description, and provides more flexibility than existing programs by allowing combinations of specific nucleotide sequences, direct and inverted repeats, variable length tandem repeats of subpatterns, and a specified number of errors in any part of the pattern. AVAILABILITY: The program is available for download and as a web service accessible through a CGI interface at http://www.cmbl.uga.edu/software.html. The source code is written in C and distributed under the GNU General Public License.

Algorithms↗

Distinguishing features of delta-proteobacterial genomes.

We analyzed several features of five currently available delta-proteobacterial genomes, including two aerobic bacteria exhibiting predatory behavior and three anaerobic sulfate-reducing bacteria. The delta genomes are distinguished from other bacteria by several properties: (i) The delta genomes contain two "giant" S1 ribosomal protein genes in contrast to all other bacterial types, which encode a single or no S1; (ii) in most delta-proteobacterial genomes the major ribosomal protein (RP) gene cluster is near the replication terminus whereas most bacterial genomes place the major RP cluster near the origin of replication; (iii) the delta genomes possess the rare combination of discriminating asparaginyl and glutaminyl tRNA synthetase (AARS) together with the amido-transferase complex (Gat CAB) genes that modify Asp-tRNA(Asn) into Asn-tRNA(Asn) and Glu-tRNA(Gln) into Gln-tRNA(Gln); (iv) the TonB receptors and ferric siderophore receptors that facilitate uptake and removal of complex metals are common among delta genomes; (v) the anaerobic delta genomes encode multiple copies of the anaerobic detoxification protein rubrerythrin that can neutralize hydrogen peroxide; and (vi) sigma(54) activators play a more important role in the delta genomes than in other bacteria. delta genomes have a plethora of enhancer binding proteins that respond to environmental and intracellular cues, often as part of two-component systems; (vii) delta genomes encode multiple copies of metallo-beta-lactamase enzymes; (viii) a host of secretion proteins emphasizing SecA, SecB, and SecY may be especially useful in the predatory activities of Myxococcus xanthus; (ix) delta proteobacteria drive many multiprotein machines in their periplasms and outer membrane, including chaperone-feeding machines, jets for slime secretion, and type IV pili. Bdellovibrio replicates in the periplasm of prey cells. The sulfate-reducing delta proteobacteria metabolize hydrogen and generate a proton gradient by electron transport. The predicted highly expressed genes from delta genomes reflect their different ecologies, metabolic strategies, and adaptations.

Amino Acyl-tRNA Synthetases↗

Analysis of distribution indicates diverse functions of simple sequence repeats in Mycoplasma genomes.

Simple sequence repeats (SSRs) composed of extensive tandem iterations of a single nucleotide or a short oligonucleotide are rare in most bacterial genomes, but they are common among Mycoplasma. Some of these repeats act as contingency loci in association with families of surface antigens. By contraction or expansion during replication, these SSRs increase genetic variance of the population and facilitate avoidance of the immune response of the host. Occurrence and distribution of SSRs are analyzed in complete genomes of 11 Mycoplasma and 3 related Mollicutes in order to gain insights into functional and evolutionary diversity of the SSRs in Mycoplasma. The results revealed an unexpected variety of SSRs with respect to their distribution and composition and suggest that it is unlikely that all SSRs function as contingency loci or recombination hot spots. Various types of SSRs are most abundant in Mycoplasma hyopneumoniae, whereas Mycoplasma penetrans, Mycoplasma mobile, and Mycoplasma synoviae do not contain unusually long SSRs. Mycoplasma hyopneumoniae and Mycoplasma pulmonis feature abundant short adenine and thymine runs periodically spaced at 11 and 12 bp, respectively, which likely affect the supercoiling propensities of the DNA molecule. Physiological roles of long adenine and thymine runs in M. hyopneumoniae appear independent of location upstream or downstream of genes, unlike contingency loci that are typically located in protein-coding regions or upstream regulatory regions. Comparisons among 3 M. hyopneumoniae strains suggest that the adenine and thymine runs are rarely involved in genome rearrangements. The results indicate that the SSRs in the Mycoplasma genomes play diverse roles, including modulating gene expression as contingency loci, facilitating genome rearrangements via recombination, affecting protein structure and possibly protein-protein interactions, and contributing to the organization of the DNA molecule in the cell.

Base Sequence↗

Genomic comparisons among gamma-proteobacteria.

Predicted highly expressed (PHX) genes are compared for 16 gamma-proteobacteria and their similarities and differences are interpreted with respect to known or predicted physiological characteristics of the organisms. Predicted highly expressed genes often reflect the organism's predominant lifestyle, habitat, nutrition sources and metabolic propensities. This technique allows to predict principal metabolic activities of the microorganisms operating in their natural habitats. Among our findings is an unusually high number of PHX enzymes acting in cell wall biosynthesis, amino acid biosynthesis and replication in the ant endosymbiont Blochmannia floridanus. We ascribe the abundance of these PHX genes to specific aspects of the relationship between the bacterium and its host. Xanthomonas campestris is unique with a very high number of PHX genes acting in flagellum biosynthesis, which may play a special role during its pathogenicity. Shewanella oneidensis possesses three protein complexes which all can function as complex I in the respiratory chain but only the Na(+)-transporting NADH:ubiquinone oxidoreductase nqr-2 operon is PHX. The PHX genes of Vibrio parahaemolyticus are consistent with the microorganism's adaptation to extremely fast growth rates. Comparative analysis of PHX genes from complex environmental genomic sequences as well as from uncultured pathogenic microbes can provide a novel, useful tool to predict global flux of matter and key intermediates.

Bacterial Proteins↗

Comparative genomic evidence for a close relationship between the dimorphic prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus.

The dimorphic prosthecate bacteria (DPB) are alpha-proteobacteria that reproduce in an asymmetric manner rather than by binary fission and are of interest as simple models of development. Prior to this work, the only member of this group for which genome sequence was available was the model freshwater organism Caulobacter crescentus. Here we describe the genome sequence of Hyphomonas neptunium, a marine member of the DPB that differs from C. crescentus in that H. neptunium uses its stalk as a reproductive structure. Genome analysis indicates that this organism shares more genes with C. crescentus than it does with Silicibacter pomeroyi (a closer relative according to 16S rRNA phylogeny), that it relies upon a heterotrophic strategy utilizing a wide range of substrates, that its cell cycle is likely to be regulated in a similar manner to that of C. crescentus, and that the outer membrane complements of H. neptunium and C. crescentus are remarkably similar. H. neptunium swarmer cells are highly motile via a single polar flagellum. With the exception of cheY and cheR, genes required for chemotaxis were absent in the H. neptunium genome. Consistent with this observation, H. neptunium swarmer cells did not respond to any chemotactic stimuli that were tested, which suggests that H. neptunium motility is a random dispersal mechanism for swarmer cells rather than a stimulus-controlled navigation system for locating specific environments. In addition to providing insights into bacterial development, the H. neptunium genome will provide an important resource for the study of other interesting biological processes including chromosome segregation, polar growth, and cell aging.

Alphaproteobacteria↗

Predicted highly expressed genes in archaeal genomes.

Based primarily on 16S rRNA sequence comparisons, life has been broadly divided into the three domains of Bacteria, Archaea, and Eukarya. Archaea is further classified into Crenarchaea and Euryarchaea. Archaea generally thrive in extreme environments as assessed by temperature, pH, and salinity. For many prokaryotic organisms, ribosomal proteins (RP), transcription/translation factors, and chaperone genes tend to be highly expressed. A gene is predicted highly expressed (PHX) if its codon usage is rather similar to the average codon usage of at least one of the RP, transcription/translation factors, and chaperone gene classes and deviates strongly from the average gene of the genome. The thermosome (Ths) chaperonin family represents the most salient PHX genes among Archaea. The chaperones Trigger factor and HSP70 have overlapping functions in the folding process, but both of these proteins are lacking in most archaea where they may be substituted by the chaperone prefoldin. Other distinctive PHX proteins of Archaea, absent from Bacteria, include the proliferating cell nuclear antigen PCNA, a replication auxiliary factor responsible for tethering the catalytic unit of DNA polymerase to DNA during high-speed replication, and the acidic RP P0, which helps to initiate mRNA translation at the ribosome. Other PHX genes feature Cell division control protein 48 (Cdc48), whereas the bacterial septation proteins FtsZ and minD are lacking in Crenarchaea. RadA is a major DNA repair and recombination protein of Archaea. Archaeal genomes feature a strong Shine-Dalgarno ribosome-binding motif more pronounced in Euryarchaea compared with Crenarchaea.

Archaea↗

Genomic and proteomic comparisons between bacterial and archaeal genomes and related comparisons with the yeast and fly genomes.

Bacterial, archaeal, yeast, and fly genomes are compared with respect to predicted highly expressed (PHX) genes and several genomic properties. There is a striking difference in the status of PHX ribosomal protein (RP) genes where the archaeal genome generally encodes more RP genes and fewer PHX RPs compared with bacterial genomes. The increase in RPs in archaea and eukaryotes compared with that in bacteria may reflect a more complex set of interactions in archaea and eukaryotes in regulating translation, e.g., differences in structure requiring scaffolding of longer rRNA molecules, expanded interactions with the chaperone machinery, and, in eukaryotic interactions with endoplasmic reticulum components. The yeast genome is similar to fast-growing bacteria in PHX genes but also features several cytoskeletal genes, including actin and tropomyosin, and several signal transduction regulatory proteins from the 14.3.3 family. The most PHX genes of Drosophila encode cytoskeletal and exoskeletal proteins. We found that the preference of a microorganism for an anaerobic metabolism correlates with the number of PHX enzymes of the glycolysis pathway that well exceeds the number of PHX enzymes acting in the tricarboxylic acid cycle. Conversely, if the number of PHX enzymes of the tricarboxylic acid cycle well exceeds the PHX enzymes of glycolysis, an aerobic metabolism is preferred. Where the numbers are approximately commensurate, a facultative growth behavior prevails.

Animals↗

Comparative analysis of gene expression among low G+C gram-positive genomes.

We present a comparative analysis of predicted highly expressed (PHX) genes in the low G+C Gram-positive genomes of Bacillus subtilis, Bacillus halodurans, Listeria monocytogenes, Listeria innocua, Lactococcus lactis, Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus aureus, Clostridium acetobutylicum, and Clostridium perfringens. Most enzymes acting in glycolysis and fermentation pathways are PHX in these genomes, but not those involved in the TCA cycle and respiration, suggesting that these organisms have predominantly adapted to grow rapidly in an anaerobic environment. Only B. subtilis and B. halodurans have several TCA cycle PHX genes, whereas the TCA pathway is entirely missing from the metabolic repertoire of the two Streptococcus species and is incomplete in Listeria, Lactococcus, and Clostridium. Pyruvate-formate lyase, an enzyme critical in mixed acid fermentation, is among the highest PHX genes in all these genomes except for C. acetobutylicum (not PHX), and B. subtilis, and B. halodurans (missing). Pyruvate-formate lyase is also prominently PHX in enteric gamma-proteobacteria, but not in other prokaryotes. Phosphotransferase system genes are generally PHX with selection of different substrates in different genomes. The various substrate specificities among phosphotransferase systems in different genomes apparently reflect on differences in habitat, lifestyle, and nutrient sources.

Energy Metabolism↗

Genome comparisons and analysis.

As we enter the post-genomic era, with the accelerating availability of complete genome sequences, new theoretical approaches and new experimental techniques, our ability to dissect cellular processes at the molecular level continues to expand. Recent advances include the application of RNA interference methods to characterize loss-of-function phenotype genes in higher eukaryotes, comparative analysis of the human and mouse genome sequences, and methods for reconciling contradictory phylogenetic reconstructions. New developments feed into the increasingly rich content of databases such as the COG database. The next phase of research will be increasingly dominated by efforts to integrate the deluge of data into our understanding of biological systems.

Amino Acid Sequence↗

Frequent oligonucleotide motifs in genomes of three streptococci.

Complete genomes of three closely related Gram-positive bacteria Streptococcus pyogenes, Streptococcus pneumoniae and Lactococcus lactis are analyzed for abundances of short DNA sequence motifs (frequent words). The character and extent of frequent words are strikingly different among these genomes. The frequent words of S.pneumoniae split into three categories: parts of the previously characterized RUP and BOX repetitive elements and a 24 bp tandem repeat in the gene SP1772. The most abundant frequent words of L.lactis are all related to the 13 bp motif, WWNTTACTGACRR or its inverted complement YYGTCAGTAANWW. Distributional analysis of this motif, which we called highly repetitive motif (HRM), indicates its possible dual role. Frequent occurrences immediately downstream of genes suggest a possible role in transcription termination whereas spacings of consecutive HRMs consistent with the DNA helical period are indicative of a protein-binding site. Two regions of the L.lactis genome feature an intriguing pattern of several periodically occurring HRMs separated by precisely 59 bp. In a striking contrast to S.pneumoniae and L.lactis, S.pyogenes contains hardly any frequent words.

Base Sequence↗

Heterogeneity of genome and proteome content in bacteria, archaea, and eukaryotes.

Our analysis compares bacteria, archaea, and eukaryota with respect to a wide assortment of genome and proteome properties. These properties include ribosomal protein gene distributions, chaperone protein contrasts, major variation of transcription/translation factors, gene encoding pathways of energy metabolism, and predicted protein expression levels. Significant differences within and between the three domains of life include protein lengths, information processing procedures, many metabolic and lipid biosynthesis pathways, cellular controls, and regulatory proteins. Differences among genomes are influenced by lifestyle, habitat, physiology, energy sources, and other factors.

Amino Acids↗