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At least 253 records · Page 14Linked to original sources
PubMed2002

Genomic analysis of C-type lectins.

Many biological effects of complex carbohydrates are mediated by lectins that contain discrete carbohydrate-recognition domains. At least seven structurally distinct families of carbohydrate-recognition domains are found in lectins that are involved in intracellular trafficking, cell adhesion, cell-cell signalling, glycoprotein turnover and innate immunity. Genome-wide analysis of potential carbohydrate-binding domains is now possible. Two classes of intracellular lectins involved in glycoprotein trafficking are present in yeast, model invertebrates and vertebrates, and two other classes are present in vertebrates only. At the cell surface, calcium-dependent (C-type) lectins and galectins are found in model invertebrates and vertebrates, but not in yeast; immunoglobulin superfamily (I-type) lectins are only found in vertebrates. The evolutionary appearance of different classes of sugar-binding protein modules parallels a development towards more complex oligosaccharides that provide increased opportunities for specific recognition phenomena. An overall picture of the lectins present in humans can now be proposed. Based on our knowledge of the structures of several of the C-type carbohydrate-recognition domains, it is possible to suggest ligand-binding activity that may be associated with novel C-type lectin-like domains identified in a systematic screen of the human genome. Further analysis of the sequences of proteins containing these domains can be used as a basis for proposing potential biological functions.

Animals↗
PubMed2006

Genomic analysis of nucleoside transporters in Diptera and functional characterization of DmENT2, a Drosophila equilibrative nucleoside transporter.

The recent completion of genome sequencing projects in a number of eukaryotes allows comparative analysis of orthologs, which can aid in identifying evolutionary constraints on protein structure and function. Nucleoside transporters (NTs) are present in a diverse array of organisms and previous studies have suggested that there is low protein sequence similarity but conserved structure in invertebrate and vertebrate NT orthologs. In addition, most taxa possess multiple NT isoforms but their respective roles in the physiology of the organism are not clear. To investigate the evolution of the structure and function of NTs, we have extended our previous studies by identifying NT orthologs in the Dipteran Anopheles gambiae and comparing these proteins to human and Drosophila melanogaster (Dm) NTs. In addition, we have functionally characterized DmENT2, one of three putative D. melanogaster ENTs that we have previously described. DmENT2 has broad substrate specificity, is insensitive to standard nucleoside transport inhibitors and is expressed in the digestive tract of late stage embryos based on in situ hybridization. DmENT1 and DmENT2 are expressed in most stages during development with the exception of early embryogenesis suggesting specific physiological roles for each isoform. These data represent the first complete genomic analysis of Dipteran NTs and the first report of the functional characterization of any Dipteran NT.

Amino Acid Sequence↗
PubMed1979

Genome analysis of Amphioxus and speculation as to the origin of contrasting vertebrate genome organization patterns.

1. The genome of Amphioxus was investigated by DNA reassociation techniques for the amount of repetitive and non-repetitive sequences and its pattern of organization. 2. A comparison of the amount of non-repetitive DNA between Amphioxus and the tunicate Ciona intestinalis does not support the hypothesis that the Cephalochordates have arisen from the Tunicates by polyploidy. 3. In the Amphioxus genome repetitive and non-repetitive elements are predominantly arranged in a short period interspersion pattern. Conclusions are presented as to the evolution of contrasting genome organization patterns among vertebrates.

Animals↗
PubMed2005

Genomic analysis of LexA binding reveals the permissive nature of the Escherichia coli genome and identifies unconventional target sites.

Genomes of eukaryotic organisms are packaged into nucleosomes that restrict the binding of transcription factors to accessible regions. Bacteria do not contain histones, but they have nucleoid-associated proteins that have been proposed to function analogously. Here, we combine chromatin immunoprecipitation and high-density oligonucleotide microarrays to define the in vivo DNA targets of the LexA transcriptional repressor in Escherichia coli. We demonstrate a near-universal relationship between the presence of a LexA sequence motif, LexA binding in vitro, and LexA binding in vivo, suggesting that a suitable recognition site for LexA is sufficient for binding in vivo. Consistent with this observation, LexA binds comparably to ectopic target sites introduced at various positions in the genome. We also identify approximately 20 novel LexA targets that lack a canonical LexA sequence motif, are not bound by LexA in vitro, and presumably require an additional factor for binding in vivo. Our results indicate that, unlike eukaryotic genomes, the E. coli genome is permissive to transcription factor binding. The permissive nature of the E. coli genome has important consequences for the nature of transcriptional regulatory proteins, biological specificity, and evolution.

Bacterial Proteins↗
PubMed1987

Molecular approaches to genome analysis: a strategy for the construction of ordered overlapping clone libraries.

Here we describe progress on a series of molecular techniques designed to bridge the gap between genetic and molecular distances in mammals. This is an essential step in the molecular cloning of genes defined by mammalian mutations, and in the molecular analysis of large regions of mammalian genomes. We summarize approaches for the physical and molecular analysis of genetic distances and describe the experimental, statistical and computational basis of a new approach to create ordered libraries of overlapping clones from large genomes.

Bayes Theorem↗
PubMed1996

Genome analysis with gene expression microarrays.

Advances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This 'chip-based' approach utilizes microscopic arrays of cDNAs printed on glass as high-density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of > 1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a single hybridization. A two-color fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass-produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics.

Animals↗
PubMed2005

Galaxy: a platform for interactive large-scale genome analysis.

Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe an interactive system, Galaxy, that combines the power of existing genome annotation databases with a simple Web portal to enable users to search remote resources, combine data from independent queries, and visualize the results. The heart of Galaxy is a flexible history system that stores the queries from each user; performs operations such as intersections, unions, and subtractions; and links to other computational tools. Galaxy can be accessed at http://g2.bx.psu.edu.

Biological Evolution↗
PubMed2005

Genomic analysis of anaerobic respiration in the archaeon Halobacterium sp. strain NRC-1: dimethyl sulfoxide and trimethylamine N-oxide as terminal electron acceptors.

We have investigated anaerobic respiration of the archaeal model organism Halobacterium sp. strain NRC-1 by using phenotypic and genetic analysis, bioinformatics, and transcriptome analysis. NRC-1 was found to grow on either dimethyl sulfoxide (DMSO) or trimethylamine N-oxide (TMAO) as the sole terminal electron acceptor, with a doubling time of 1 day. An operon, dmsREABCD, encoding a putative regulatory protein, DmsR, a molybdopterin oxidoreductase of the DMSO reductase family (DmsEABC), and a molecular chaperone (DmsD) was identified by bioinformatics and confirmed as a transcriptional unit by reverse transcriptase PCR analysis. dmsR, dmsA, and dmsD in-frame deletion mutants were individually constructed. Phenotypic analysis demonstrated that dmsR, dmsA, and dmsD are required for anaerobic respiration on DMSO and TMAO. The requirement for dmsR, whose predicted product contains a DNA-binding domain similar to that of the Bat family of activators (COG3413), indicated that it functions as an activator. A cysteine-rich domain was found in the dmsR gene, which may be involved in oxygen sensing. Microarray analysis using a whole-genome 60-mer oligonucleotide array showed that the dms operon is induced during anaerobic respiration. Comparison of dmsR+ and DeltadmsR strains by use of microarrays showed that the induction of the dmsEABCD operon is dependent on a functional dmsR gene, consistent with its action as a transcriptional activator. Our results clearly establish the genes required for anaerobic respiration using DMSO and TMAO in an archaeon for the first time.

Anaerobiosis↗
PubMed2005

Functional genomic analysis of cancer metastasis: biologic insights and clinical implications.

Metastasis, the spread of cancer from primary tumors to distant vital organs, has devastating consequences. Lack of effective tools to study this complex problem has hindered the development of accurate prognostic methods and effective treatments for metastatic cancer. In the postgenomic era, the application of genomic profiling methods to the analysis of clinical metastasis samples and animal metastasis models has revolutionized the field of metastasis research. This article reviews recent breakthroughs in the functional genomic analysis of metastasis. In addition, its impacts on our understanding of the molecular basis of metastasis and on clinical practice are discussed.

Animals↗
PubMed2004

A comparative genome analysis identifies distinct sorting pathways in gram-positive bacteria.

Surface proteins in gram-positive bacteria are frequently required for virulence, and many are attached to the cell wall by sortase enzymes. Bacteria frequently encode more than one sortase enzyme and an even larger number of potential sortase substrates that possess an LPXTG-type cell wall sorting signal. In order to elucidate the sorting pathways present in gram-positive bacteria, we performed a comparative analysis of 72 sequenced microbial genomes. We show that sortase enzymes can be partitioned into five distinct subfamilies based upon their primary sequences and that most of their substrates can be predicted by making a few conservative assumptions. Most bacteria encode sortases from two or more subfamilies, which are predicted to function nonredundantly in sorting proteins to the cell surface. Only approximately 20% of sortase-related proteins are most closely related to the well-characterized Staphylococcus aureus SrtA protein, but nonetheless, these proteins are responsible for anchoring the majority of surface proteins in gram-positive bacteria. In contrast, most sortase-like proteins are predicted to play a more specialized role, with each anchoring far fewer proteins that contain unusual sequence motifs. The functional sortase-substrate linkage predictions are available online (http://www.doe-mbi.ucla.edu/Services/Sortase/) in a searchable database.

Amino Acid Motifs↗
PubMed2004

Fractal genomics modeling: a new approach to genomic analysis and biomarker discovery.

Reverse engineering of genetics networks generally requires establishing correlative behavior within and between a very large number of genes. This becomes a difficult analytical problem for even a few hundred genes and the difficulty tends to grow exponentially as more genes are examined. Using a hybrid data analysis method known as Fractal Genomics Modeling (FGM), this problem is reduced to examining correlative behavior within small gene groups that can then be compared and integrated to produce a picture of larger networks using a type pf shotgun approach. We have applied FGM toward examining genetic networks involved in HIV infection in the brain. These networks have relevance both to processes related to HIV infection and neurodegenerative disorders. Our preliminary findings have produced conjectures of related pathways and networks as well new candidates for genetic markers in HIV brain infection. Evidence has also been produced which appears to show the presence of a hierarchical network structure within the genes studied. We will discuss the background and methodology of FGM as well as our recent findings.

AIDS Dementia Complex↗
PubMed2005

[Genome analysis and cancer therapy].

Application of the human genome information would lead to the development of novel diagnostic methods and innovative therapies against cancer. In this article, two aspects of such application are reviewed; 1) genomic diagnosis for predicting efficacy and side effects associated with the administration of the anti-cancer drugs, 2) exploration of novel cancer associated gene products using genome-wide gene-expression profiling. Successful examination on genetic information of the patients/tumors would lead to the establishment of the "personalized" medicine which could be an ideal situation for the cancer patients treated with the chemotherapeutic drugs. Furthermore, the finding of tumor associated antigens lead to the development of not only new diagnostic methods but also novel therapeutic modalities including cancer vaccine. Some of the successful efforts are referred and discussed.

Antineoplastic Agents↗
PubMed2005

Full-genome analysis of a highly divergent simian T-cell lymphotropic virus type 1 strain in Macaca arctoides.

Full-genome sequencing and analysis of the highly divergent simian T-cell lymphotropic virus type 1 (STLV-1) strain MarB43 in Macaca arctoides indicated that its open reading frame structure is compatible with proper functioning of its Gag, Pol, Env, Tax and Rex proteins. Detailed analysis of the coding potential, however, revealed that MarB43 is probably forced to use the human T-cell lymphotropic virus type 2/STLV-2 env-tax-rex splice-acceptor homologue and that the proximal pX auxiliary proteins p12(I), p13(II), p30(II) and p27(I) seem to have lost their function. Full-genome (gag-pol-env-tax), long terminal repeat and env phylogenetic analyses conclusively identified STLV-1 in M. arctoides as the currently most divergent STLV-1 strain. The long branching pattern of the monophyletic STLV-1 Macaca subspecies clades suggests that macaques might be the ancestral reservoir for primate T-cell lymphotropic virus type 1 in Asia. Full-genome molecular-clock analysis supports an archaic introduction of STLV-1 on the Asian continent, at least 269 000-156 000 years ago.

Animals↗
PubMed2004

Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome.

Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXRbeta suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection.

Amino Acid Sequence↗
PubMed1997

Complete sequence and genomic analysis of murine gammaherpesvirus 68.

Murine gammaherpesvirus 68 (gammaHV68) infects mice, thus providing a tractable small-animal model for analysis of the acute and chronic pathogenesis of gammaherpesviruses. To facilitate molecular analysis of gammaHV68 pathogenesis, we have sequenced the gammaHV68 genome. The genome contains 118,237 bp of unique sequence flanked by multiple copies of a 1,213-bp terminal repeat. The GC content of the unique portion of the genome is 46%, while the GC content of the terminal repeat is 78%. The unique portion of the genome is estimated to encode at least 80 genes and is largely colinear with the genomes of Kaposi's sarcoma herpesvirus (KSHV; also known as human herpesvirus 8), herpesvirus saimiri (HVS), and Epstein-Barr virus (EBV). We detected 63 open reading frames (ORFs) homologous to HVS and KSHV ORFs and used the HVS/KSHV numbering system to designate these ORFs. gammaHV68 shares with HVS and KSHV ORFs homologous to a complement regulatory protein (ORF 4), a D-type cyclin (ORF 72), and a G-protein-coupled receptor with close homology to the interleukin-8 receptor (ORF 74). One ORF (K3) was identified in gammaHV68 as homologous to both ORFs K3 and K5 of KSHV and contains a domain found in a bovine herpesvirus 4 major immediate-early protein. We also detected 16 methionine-initiated ORFs predicted to encode proteins at least 100 amino acids in length that are unique to gammaHV68 (ORFs M1 to 14). ORF M1 has striking homology to poxvirus serpins, while ORF M11 encodes a potential homolog of Bcl-2-like molecules encoded by other gammaherpesviruses (gene 16 of HVS and KSHV and the BHRF1 gene of EBV). In addition, clustered at the left end of the unique region are eight sequences with significant homology to bacterial tRNAs. The unique region of the genome contains two internal repeats: a 40-bp repeat located between bp 26778 and 28191 in the genome and a 100-bp repeat located between bp 98981 and 101170. Analysis of the gammaHV68, HVS, EBV, and KSHV genomes demonstrated that each of these viruses have large colinear gene blocks interspersed by regions containing virus-specific ORFs. Interestingly, genes associated with EBV cell tropism, latency, and transformation are all contained within these regions encoding virus-specific genes. This finding suggests that pathogenesis-associated genes of gammaherpesviruses, including gammaHV68, may be contained in similarly positioned genome regions. The availability of the gammaHV68 genomic sequence will facilitate analysis of critical issues in gammaherpesvirus biology via integration of molecular and pathogenetic studies in a small-animal model.

Amino Acid Sequence↗
PubMed2002

Genomic analysis of the terpenoid synthase ( AtTPS) gene family of Arabidopsis thaliana.

A family of 40 terpenoid synthase genes ( AtTPS) was discovered by genome sequence analysis in Arabidopsis thaliana. This is the largest and most diverse group of TPS genes currently known for any species. AtTPS genes cluster into five phylogenetic subfamilies of the plant TPS superfamily. Surprisingly, thirty AtTPS closely resemble, in all aspects of gene architecture, sequence relatedness and phylogenetic placement, the genes for plant monoterpene synthases, sesquiterpene synthases or diterpene synthases of secondary metabolism. Rapid evolution of these AtTPS resulted from repeated gene duplication and sequence divergence with minor changes in gene architecture. In contrast, only two AtTPS genes have known functions in basic (primary) metabolism, namely gibberellin biosynthesis. This striking difference in rates of gene diversification in primary and secondary metabolism is relevant for an understanding of the evolution of terpenoid natural product diversity. Eight AtTPS genes are interrupted and are likely to be inactive pseudogenes. The localization of AtTPS genes on all five chromosomes reflects the dynamics of the Arabidopsis genome; however, several AtTPS genes are clustered and organized in tandem repeats. Furthermore, some AtTPS genes are localized with prenyltransferase genes ( AtGGPPS, geranylgeranyl diphosphate synthase) in contiguous genomic clusters encoding consecutive steps in terpenoid biosynthesis. The clustered organization may have implications for TPS gene evolution and the evolution of pathway segments for the synthesis of terpenoid natural products. Phylogenetic analyses highlight events in the divergence of the TPS paralogs and suggest orthologous genes and a model for the evolution of the TPS gene family.

Alkyl and Aryl Transferases↗
PubMed2000

Comparative genome analysis of the pathogenic spirochetes Borrelia burgdorferi and Treponema pallidum.

A comparative analysis of the predicted protein sequences encoded in the complete genomes of Borrelia burgdorferi and Treponema pallidum provides a number of insights into evolutionary trends and adaptive strategies of the two spirochetes. A measure of orthologous relationships between gene sets, termed the orthology coefficient (OC), was developed. The overall OC value for the gene sets of the two spirochetes is about 0.43, which means that less than one-half of the genes show readily detectable orthologous relationships. This emphasizes significant divergence between the two spirochetes, apparently driven by different biological niches. Different functional categories of proteins as well as different protein families show a broad distribution of OC values, from near 1 (a perfect, one-to-one correspondence) to near 0. The proteins involved in core biological functions, such as genome replication and expression, typically show high OC values. In contrast, marked variability is seen among proteins that are involved in specific processes, such as nutrient transport, metabolism, gene-specific transcription regulation, signal transduction, and host response. Differences in the gene complements encoded in the two spirochete genomes suggest active adaptive evolution for their distinct niches. Comparative analysis of the spirochete genomes produced evidence of gene exchanges with other bacteria, archaea, and eukaryotic hosts that seem to have occurred at different points in the evolution of the spirochetes. Examples are presented of the use of sequence profile analysis to predict proteins that are likely to play a role in pathogenesis, including secreted proteins that contain specific protein-protein interaction domains, such as von Willebrand A, YWTD, TPR, and PR1, some of which hitherto have been reported only in eukaryotes. We tentatively reconstruct the likely evolutionary process that has led to the divergence of the two spirochete lineages; this reconstruction seems to point to an ancestral state resembling the symbiotic spirochetes found in insect guts.

Amino Acid Sequence↗