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Results for “structural genomics”

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PubMed1994

Genomic structure of human adrenomedullin gene.

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered from human pheochromocytoma tissue by its stimulating activity of platelet cAMP production. In this study, we have isolated the gene for human AM from a human genomic library and determined its structure. The genomic DNA of human AM consists of 4 exons and 3 introns, and the 5' flanking region contains TATA, CAAT and GC boxes. There are also multiple binding sites for activator protein-2 (AP-2) and a cAMP-regulated enhancer element. Southern blot analyses revealed that the AM gene is situated in a single locus of chromosome 11. These indicate that the human AM gene has components for its functional expression and that the expression may be subject to the activity of protein kinase C and the feedback from cAMP level.

Adrenal Gland Neoplasms↗

PubMed2000

Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non-ribosomal peptide synthetase.

A gene cluster for the non-ribosomal synthesis of a peptide of unknown structure has been identified in the partial genome sequence of Streptomyces coelicolor. Using molecular and computational analyses, the total structure of a tripeptide siderophore synthesized by the non-ribosomal peptide synthetase within the cluster has been deduced from the translated sequence of its encoding gene. This represents a novel method for the structural assignment of natural products from genome sequence data.

Amino Acid Motifs↗

PubMed2026

Assembly and comparative analysis of the mitochondrial genome of Pleione yunnanensis: genome structure and evolutionary insights.

BACKGROUND: Pleione yunnanensis a terrestrial or semi-epiphytic herbaceous plant belonging to the Orchidaceae family, is valued for both its medicinal uses and ornamental appeal. Although its chloroplast genomes have been sequenced, its complete mt genome had not previously been resolved, limiting genetic and evolutionary studies of the species. RESULTS: In this work, we assembled and characterized the first complete mt genome of P. yunnanensis, revealing a structurally complex, multibranched system composed of 14 circular-mapping molecules totaling 468,176 bp with a GC content of 44.32%. The genome encodes 44 annotated genes, including 28 protein-coding genes (PCGs), 15 tRNAs, and one rRNA. The multibranched architecture provides new evidence supporting the dynamic and recombinational nature of plant mt genomes. Repeat analysis uncovered 29 simple sequence repeats (SSRs), 19 tandem repeats, and 118 dispersed repeats, indicating a comparatively lower repeat abundance than that found in closely related orchids with similar mt genome sizes. Codon-usage profiling of PCGs showed a marked bias toward A/T-ending codons. Prediction of RNA editing sites identified 4,708 putative edits across mitochondrial PCGs. Most mitochondrial genes displayed Ka/Ks ratios close to 1.0, suggesting relaxed selective constraints or lineage-specific evolutionary patterns rather than strong positive selection. Moreover, we detected 69 chloroplast-derived homologous fragments, including 15 intact genes, suggesting ongoing plastid-mitochondrial DNA transfer. Phylogenetic reconstruction and collinearity comparisons demonstrated that P. yunnanensis clustered closely with Dendrobium species, including D. amplum and D. hancockii, within the Orchidaceae clade. CONCLUSIONS: This study provides the first complete mt genome of P. yunnanensis, providing a foundational genomic resource for the genus Pleione. The results not only improve our understanding of mt genome structure and evolution in Orchidaceae, but also offer valuable molecular evidence for phylogenetic inference, germplasm identification, and conservation of this endangered medicinal species.

Orchidaceae↗

PubMed1999

The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability.

Increasing evidence has accumulated for an involvement of the inactivation of tumour suppressor genes at chromosome 10q in the carcinogenesis of brain tumours, melanomas, and carcinomas of the lung, the prostate, the pancreas, and the endometrium. The gene DMBT1 (Deleted in Malignant Brain Tumours 1) is located at chromosome 10q25.3-q26.1, within one of the putative intervals for tumour suppressor genes. DMBT1 is a member of the scavenger-receptor cysteine-rich (SRCR) superfamily and displays homozygous deletions or lack of expression in glioblastoma multiforme, medulloblastoma, and in gastrointestinal and lung cancers. Based on these properties, DMBT1 has been proposed to be a candidate tumour suppressor gene. We have determined the genomic sequence of DMBT1 to allow analyses of mutations. The gene has at least 54 exons that span a genomic region of about 80 kb. We have identified a putative exon with coding potential for a transmembrane domain. Our data further suggest that alternative splicing gives rise to isoforms of DMBT1 with a differential utilization of SRCR domains and SRCR interspersed domains. The major part of the gene harbours locus specific repeats. These repeats may point to the DMBT1 locus as a region susceptible to chromosomal instability.

Agglutinins↗

PubMed1999

Origin, genetic diversity, and genome structure of the domestic dog.

Comparative analysis of mammalian genomes provides important insight into the structure and function of genes. However, the comparative analysis of gene sequences from individuals of the same and different species also provides insight into the evolution of genes, populations, and species. We exemplify these two uses of genomic information. First, we document the evolutionary relationships of the domestic dog to other carnivores by using a variety of DNA-based information. A phylogenetic comparison of mitochondrial DNA sequences in dogs and gray wolves shows that dogs may have originated from multiple wolf populations at a time much earlier than suggested by the archaeologic record. We discuss previous theories about dog development and evolution in light of the new genetic data. Second, we review recent progress in dog genetic mapping due to the development of hypervariable markers and specific chromosome paints. Extensive genetic homology in gene order and function between humans and dogs has been discovered. The dog promises to be a valuable model for identifying genes that control morphologic differences between mammals as well as understanding genetically based disease.

Animals↗

PubMed2006

Coverage of whole proteome by structural genomics observed through protein homology modeling database.

We have been developing FAMSBASE, a protein homology-modeling database of whole ORFs predicted from genome sequences. The latest update of FAMSBASE ( http://daisy.nagahama-i-bio.ac.jp/Famsbase/ ), which is based on the protein three-dimensional (3D) structures released by November 2003, contains modeled 3D structures for 368,724 open reading frames (ORFs) derived from genomes of 276 species, namely 17 archaebacterial, 130 eubacterial, 18 eukaryotic and 111 phage genomes. Those 276 genomes are predicted to have 734,193 ORFs in total and the current FAMSBASE contains protein 3D structure of approximately 50% of the ORF products. However, cases that a modeled 3D structure covers the whole part of an ORF product are rare. When portion of an ORF with 3D structure is compared in three kingdoms of life, in archaebacteria and eubacteria, approximately 60% of the ORFs have modeled 3D structures covering almost the entire amino acid sequences, however, the percentage falls to about 30% in eukaryotes. When annual differences in the number of ORFs with modeled 3D structure are calculated, the fraction of modeled 3D structures of soluble protein for archaebacteria is increased by 5%, and that for eubacteria by 7% in the last 3 years. Assuming that this rate would be maintained and that determination of 3D structures for predicted disordered regions is unattainable, whole soluble protein model structures of prokaryotes without the putative disordered regions will be in hand within 15 years. For eukaryotic proteins, they will be in hand within 25 years. The 3D structures we will have at those times are not the 3D structure of the entire proteins encoded in single ORFs, but the 3D structures of separate structural domains. Measuring or predicting spatial arrangements of structural domains in an ORF will then be a coming issue of structural genomics.

Amino Acid Sequence↗

PubMed1993

Integration of repeated sequences (pBR322) in the Bacillus subtilis 168 chromosome without affecting the genome structure.

The Escherichia coli plasmid pBR322 sequence (4363 bp) was integrated at the met, pro, or leuB locus of the Bacillus subtilis chromosome without duplication of the flanking chromosomal regions. The integrated pBR322 was stably maintained as part of the chromosome regardless of its orientation or location. It was found that a DNA segment as large as 17 kb cloned in pBR322 can be readily transferred to the B. subtilis chromosome by transformation. It was demonstrated that a second pBR322 sequence could be effectively introduced at different regions of the chromosome by sequential transformation using chromosomal DNA isolated from a strain that had already acquired a pBR322 sequence at a different locus. Similarly, a third pBR322 sequence could be introduced. By this method, two or three pBR322 sequences can be incorporated at unlinked loci without affecting the overall structure of the B. subtilis genome.

Bacillus subtilis↗

PubMed1992

Genomic structure of the gene for copper/zinc-superoxide dismutase in rice.

We have isolated and determined the nucleotide sequence of the structural gene (sodB) coding for one of the copper/zinc-superoxide dismutase (Cu/Zn-SOD) isozymes from rice plants (Oryza sativa L.). The sodB gene is split into 8 exons spread about 2 kb of the chromosomal DNA, with the coding sequence beginning in the 2nd and ending in the 8th. Although none of sodB introns are inserted into similar positions in Cu/Zn-SOD genes from other sources, four of six introns in the protein-coding region are located at discriminating positions within structural domains of the protein. Genomic Southern analysis indicated that cytosolic Cu/Zn-SOD is coded for by 2-3 genes in the rice genome.

Amino Acid Sequence↗

PubMed1996

Comparison of the human genomic structure of the Runt domain-encoding PEBP2/CBFalpha gene family.

We cloned the human cDNA corresponding to the cDNA (PEBP2alphaB-451) encoding the mouse polyomavirus enhancer-binding protein 2alphaB-451, representing a major splice variant from acute myeloid leukemia gene 1 (AML1). Genomic DNA clones of AML1 were also isolated and the exon/intron structure was determined. Furthermore, we determined and compared the genomic structures of three mammalian Runt domain-containing genes, PEBP2alphaA,AML/PEBE2alphaB and PEBP2alphaC.

Acute Disease↗

PubMed2001

Protein structure prediction and structural genomics.

Genome sequencing projects are producing linear amino acid sequences, but full understanding of the biological role of these proteins will require knowledge of their structure and function. Although experimental structure determination methods are providing high-resolution structure information about a subset of the proteins, computational structure prediction methods will provide valuable information for the large fraction of sequences whose structures will not be determined experimentally. The first class of protein structure prediction methods, including threading and comparative modeling, rely on detectable similarity spanning most of the modeled sequence and at least one known structure. The second class of methods, de novo or ab initio methods, predict the structure from sequence alone, without relying on similarity at the fold level between the modeled sequence and any of the known structures. In this Viewpoint, we begin by describing the essential features of the methods, the accuracy of the models, and their application to the prediction and understanding of protein function, both for single proteins and on the scale of whole genomes. We then discuss the important role that protein structure prediction methods play in the growing worldwide effort in structural genomics.

Amino Acid Sequence↗

PubMed1997

Genomic structure of a novel LIM domain gene (ZNF185) in Xq28 and comparisons with the orthologous murine transcript.

Construction of a transcript map in the DXS52 region in Xq28 had previously led to the isolation of a cDNA with a LIM zinc finger domain in the carboxyl terminus. In parallel, the orthologous murine transcript was isolated from the syntenic region. The human and mouse cDNAs have been designated ZNF185 and Zfp185, respectively. By integrating the cDNA sequence with the cosmid-derived genomic sequence the exon-intron structure of the 3' end of the ZNF185 gene was resolved. Comparative sequence analyses of the human genomic sequence with the full-length murine cDNA facilitated prediction of the 5' end of the gene. The selective expression of three transcripts corresponding to the ZNF185 gene and a related gene was shown by Northern and Southern blots. In situ hybridizations revealed a nonubiquitous and stage-specific expression of Zfp185, especially in differentiating connective tissue. Since LIM proteins regulate cellular proliferation and/or differentiation by diverse mechanisms, and some have directly been associated with disease, conceivably ZNF185 may represent a candidate for a disease-causing gene linked to Xq28. Knowledge of the genomic structure will permit detailed mutation analyses.

Amino Acid Sequence↗

PubMed1998

Characterization of gene expression, genomic structure, and chromosomal localization of Hells (Lsh).

Hells (Lsh) is a lymphoid-specific presumptive helicase with highest expression in lymphoid precursor cells. Other members of the helicase family participate in maintenance of genome stability, DNA repair, and transcriptional control. Here we report the structure and chromosomal location of the Hells gene. The open reading frame of the murine Hells gene spans at least 26.6 kb of chromosomal DNA and is composed of 18 exons. The genomic structure of the seven helicase domains closely resembles that of mammalian Rad54, a gene whose product appears to be involved in recombination and double-strand break repair. The human homologue, the HELLS gene, has a mRNA expression pattern that is similar to murine Hells expression. Low-stringency hybridization in a Southern analysis reveals homologous Hells genes in a variety of species including Saccharomyces cerevisiae. FISH analysis maps the murine Hells gene to region C3-D1 on chromosome 19. The human homologue maps to a region of synteny on chromosome 10q23-q24, a breakpoint region frequently involved in human leukemia.

Animals↗

PubMed2006

sgTarget: a target selection resource for structural genomics.

sgTarget (http://www.ysbl.york.ac.uk/sgTarget) is a web-based resource to aid the selection and prioritization of candidate proteins for structure determination. The system annotates user submitted gene or protein sequences, identifying sequence families with no homologues of known structure, and characterizing each protein according to a range of physicochemical properties that may affect its expression, solubility and likelihood to crystallize. Summaries of these analyses are available for individual sequences, as well as whole datasets. This type of analysis enables structural biologists to iteratively select targets from their genomic sequences of interest and according to their research needs. All sequence datasets submitted to sgTarget are available for users to select and rank using their choice of criteria. sgTarget was developed to support individual laboratories collaborating in structural and functional genomics projects and should be valuable to structural biologists wishing to employ the wealth of available genome sequences in their structural quests.

Animals↗

PubMed2003

Structural genomics of proteins involved in copper homeostasis.

Genome sequencing projects have provided a wealth of data, most notably the primary sequences of all the proteins that a given organism can produce. The understanding of this information at the functional level is still in the beginning stages. Three-dimensional structural information is necessary to unravel at the atomic level the mechanisms by which a protein carries out its function, and such information can often be very useful to predict at least gross functional features, even in the absence of biochemical data. An exhaustive structural characterization of the proteins encoded in the genomes is thus highly desirable. To enhance the functional insights provided by genome-scale structural determination, we have prioritized our research to target specific processes of the cell, i.e., those responsible for controlling metal homeostasis. In this Account, we present the results obtained by the Magnetic Resonance Center of the University of Florence on proteins involved in the homeostasis of copper. The general research strategy is presented, followed by a discussion focused on different key experimental aspects. An overview of the initial results and of their relevance to the understanding of molecular function and cellular processes is also given.

Carrier Proteins↗

PubMed1996

Molecular analysis of the genomic structure of the human Y chromosome in the euchromatic part of its long arm (Yq11).

Conventional methods of long range restriction mapping for analysis of the genomic DNA structure failed in Yq11, because single-copy DNA probes for blot hybridization analyses are rare and the rate of DNA methylation is high in this Y region. Numerous repetitive sequence blocks of unknown extensions are scattered throughout Yq11 and a patchwork of X-Y homologous DNA blocks were found by different investigators. Therefore, our approach towards a molecular analysis of this Y region reduced this complexity by performing first its molecular analysis in YAC clones mapping to Yq11. YACs contain only a part of the whole Yq11 DNA structure. In this paper, we present our first results of this approach based on quantitative blot analysis of 51 DNA loci in 67 YAC clones. The YACs were isolated from the three CEPH libraries and mapped to a contig of 13 Mb from proximal to distal Yq11 with aid of a detailed interval map. In distal Yq11, our analysis revealed the presence of local amplification events of different DNA domains. A model of their possible arrangement is presented.

Chromatin↗

PubMed2005

Wheat genome structure: translocations during the course of polyploidization.

The genomic organization of Triticum timopheevii (2n=28, AtAtGG) was compared with hexaploid wheat T. aestivum (2n=42, AABBDD) by comparative mapping using microsatellites derived from bread wheat. Genetic maps for the two crosses T. timopheevii var. timopheevii x T. timopheevii var. typica and T. timopheevii K-38555xT. militinae were constructed. On the first population, 121 loci were mapped, and on the second population 103 loci. The transferability of the wheat markers to T. timopheevii was generally better for the A genome-specific markers (76-78% produced amplification products; 26 and 29% were polymorphic) than for B genome-specific markers (54% produced amplification products; 14 and 16% were polymorphic). Of the D genome-specific markers, one third produced amplification products in T. timopheevii, but only 5 and 2% were polymorphic in the corresponding mapping populations. The maps constructed confirmed the previously described translocation between chromosome arms 6AtS and 1GS and revealed at least two yet unknown rearrangements on chromosomes 4At and 6At09. The presence of other translocations and rearrangements between T. timopheevii and T. aestivum was demonstrated by a variety of markers mapping to nonhomoeologous positions.

Chromosome Mapping↗

PubMed2006

Characterization of the genome structure of Bombyx mori densovirus (China isolate).

The genome of Bombyx mori densovirus (China isolate), termed as BmDNV-3, is composed of two kinds of different single-stranded linear DNA molecules (VD1 and VD2). In this study, the viral DNA molecules were purified and cloned into pUC119 vector, and the complete nucleotide sequence was determined. Sequence analysis showed that VD1 genome consisted of 6,543 nts including inverted terminal repeats (ITRs) of 224 nts, and VD2 genome consisted of 6,022 nts including ITRs of 524 nts. Comparison of the complete genome sequence between BmDNV-3 and BmDNV-2 (Yamanashi isolate) showed an identity of 98.4% in VD1 and 97.7% in VD2, with a total number of 228 bp substitutions, 11 bp deletions and 3 bp insertions found in BmDNV-3. A single nucleotide "A" deletion at nt 1589 in BmDNV-3 caused a frame shift mutation and brought about a premature stop codon, thus dividing VD2 of BmDNV-3 into two ORFs (named VD2 ORF1a and VD2 ORF1b) within that region, while there was only one ORF (named VD2 ORF1) in the corresponding region of BmDNV-2 (Yamanashi isolate). Comparative polymorphisms of ORFs and ITR regions of the two viral genomes showed that highly variable regions were mainly located in VD1 ORF3, VD1 ORF4, VD2 ORF2, and ITRs of BmDNV-3. Northern blots analysis revealed that VD1 had 1.1 kb and 1.5 kb transcripts from the left half of its plus strand, and one transcript about 3.3 kb from the right half of its minus strand. Sequencing of 3' and 5' RACE products showed that the 1.1 kb transcript started at nt 290 and ended at nt 1437, the 1.5 kb transcript started at nt 1423 and ended at nt 2931, and the 3.3 kb transcript started at nt 6287 and ended at nt 2922. These results help us to further understand the variation between different DNV genera and its possible causes, providing clues for studying the evolutionary history of densoviruses.

Amino Acid Sequence↗

PubMed2005

Diversity of genome structure in Salmonella enterica serovar Typhi populations.

The genomes of most strains of Salmonella and Escherichia coli are highly conserved. In contrast, all 136 wild-type strains of Salmonella enterica serovar Typhi analyzed by partial digestion with I-CeuI (an endonuclease which cuts within the rrn operons) and pulsed-field gel electrophoresis and by PCR have rearrangements due to homologous recombination between the rrn operons leading to inversions and translocations. Recombination between rrn operons in culture is known to be equally frequent in S. enterica serovar Typhi and S. enterica serovar Typhimurium; thus, the recombinants in S. enterica serovar Typhi, but not those in S. enterica serovar Typhimurium, are able to survive in nature. However, even in S. enterica serovar Typhi the need for genome balance and the need for gene dosage impose limits on rearrangements. Of 100 strains of genome types 1 to 6, 72 were only 25.5 kb off genome balance (the relative lengths of the replichores during bidirectional replication from oriC to the termination of replication [Ter]), while 28 strains were less balanced (41 kb off balance), indicating that the survival of the best-balanced strains was greater. In addition, the need for appropriate gene dosage apparently selected against rearrangements which moved genes from their accustomed distance from oriC. Although rearrangements involving the seven rrn operons are very common in S. enterica serovar Typhi, other duplicated regions, such as the 25 IS200 elements, are very rarely involved in rearrangements. Large deletions and insertions in the genome are uncommon, except for deletions of Salmonella pathogenicity island 7 (usually 134 kb) from fragment I-CeuI-G and 40-kb insertions, possibly a prophage, in fragment I-CeuI-E. The phage types were determined, and the origins of the phage types appeared to be independent of the origins of the genome types.

Chromosomes, Bacterial↗