Biomedical subjects

Kim Brügger

Publications and source records attributed to Kim Brügger.

11 recordsLinked to original sources

PubMed2006

The Sulfolobus database.

The Sulfolobus database (http://www.sulfolobus.org) integrates, for the first time, all currently available Sulfolobus chromosome sequences with annotations. It also includes all the sequence data for the extrachromosomal elements which can propagate in Sulfolobus organisms. All genomes and annotations deposited in GenBank are included in the database and a genefinder has been run on the sequences to ensure that all potential genes are present, and identifiable, in the database. Every month, all genes are searched against a range of external databases and new results are incorporated. The Sulfolobus database was developed as an asset to the rapidly-growing international community working with Sulfolobus as a model organism for the kingdom Crenarchaeota of the Archaea. It was accessed more that 46 000 times in its first year. The database aims to provide researchers easy access to sequence and gene information and the web-interface includes various searches, free text and BLAST, as well as genome browsing and data extraction. Updated annotations are incorporated regularly and the database will continue to expand as new information becomes available. This includes new sequences, newly identified genes, annotations and other related information.

Chromosomes, Archaeal↗

PubMed2006

A putative viral defence mechanism in archaeal cells.

Clusters of regularly spaced direct repeats, separated by unconserved spacer sequences, are ubiquitous in archaeal chromosomes and occur in some plasmids. Some clusters constitute around 1% of chromosomal DNA. Similarly structured clusters, generally smaller, also occur in some bacterial chromosomes. Although early studies implicated these clusters in segregation/partition functions, recent evidence suggests that the spacer sequences derive from extrachromosomal elements, and, primarily, viruses. This has led to the proposal that the clusters provide a defence against viral propagation in cells, and that both the mode of inhibition of viral propagation and the mechanism of adding spacer-repeat units to clusters, are dependent on RNAs transcribed from the clusters. Moreover, the putative inhibitory apparatus (piRNA-based) may be evolutionarily related to the interference RNA systems (siRNA and miRNA), which are common in eukarya. Here, we analyze all the current data on archaeal repeat clusters and provide some new insights into their diverse structures, transcriptional properties and mode of structural development. The results are consistent with larger cluster transcripts being processed at the centers of the repeat sequences and being further trimmed by exonucleases to yield a dominant, intracellular RNA species, which corresponds approximately to the size of a spacer. Furthermore, analysis of the extensive clusters of Sulfolobus solfataricus strains P1 and P2B provides support for the presence of a flanking sequence adjoining a cluster being a prerequisite for the incorporation of new spacer-repeat units, which occurs between the flanking sequence and the cluster. An archaeal database summarizing the data will be maintained at http://dac.molbio.ku.dk/dbs/SRSR/.

Archaea↗

PubMed2005

Structure and genome organization of AFV2, a novel archaeal lipothrixvirus with unusual terminal and core structures.

A novel filamentous virus, AFV2, from the hyperthermophilic archaeal genus Acidianus shows structural similarity to lipothrixviruses but differs from them in its unusual terminal and core structures. The double-stranded DNA genome contains 31,787 bp and carries eight open reading frames homologous to those of other lipothrixviruses, a single tRNA(Lys) gene containing a 12-bp archaeal intron, and a 1,008-bp repeat-rich region near the center of the genome.

Genome, Viral↗

PubMed2005

The genome of Sulfolobus acidocaldarius, a model organism of the Crenarchaeota.

Sulfolobus acidocaldarius is an aerobic thermoacidophilic crenarchaeon which grows optimally at 80 degrees C and pH 2 in terrestrial solfataric springs. Here, we describe the genome sequence of strain DSM639, which has been used for many seminal studies on archaeal and crenarchaeal biology. The circular genome carries 2,225,959 bp (37% G+C) with 2,292 predicted protein-encoding genes. Many of the smaller genes were identified for the first time on the basis of comparison of three Sulfolobus genome sequences. Of the protein-coding genes, 305 are exclusive to S. acidocaldarius and 866 are specific to the Sulfolobus genus. Moreover, 82 genes for untranslated RNAs were identified and annotated. Owing to the probable absence of active autonomous and nonautonomous mobile elements, the genome stability and organization of S. acidocaldarius differ radically from those of Sulfolobus solfataricus and Sulfolobus tokodaii. The S. acidocaldarius genome contains an integrated, and probably encaptured, pARN-type conjugative plasmid which may facilitate intercellular chromosomal gene exchange in S. acidocaldarius. Moreover, it contains genes for a characteristic restriction modification system, a UV damage excision repair system, thermopsin, and an aromatic ring dioxygenase, all of which are absent from genomes of other Sulfolobus species. However, it lacks genes for some of their sugar transporters, consistent with it growing on a more limited range of carbon sources. These results, together with the many newly identified protein-coding genes for Sulfolobus, are incorporated into a public Sulfolobus database which can be accessed at http://dac.molbio.ku.dk/dbs/Sulfolobus.

Base Sequence↗

PubMed2005

Novel RepA-MCM proteins encoded in plasmids pTAU4, pORA1 and pTIK4 from Sulfolobus neozealandicus.

Three plasmids isolated from the crenarchaeal thermoacidophile Sulfolobus neozealandicus were characterized. Plasmids pTAU4 (7,192 bp), pORA1 (9,689 bp) and pTIK4 (13,638 bp) show unusual properties that distinguish them from previously characterized cryptic plasmids of the genus Sulfolobus. Plasmids pORA1 and pTIK4 encode RepA proteins, only the former of which carries the novel polymerase-primase domain of other known Sulfolobus plasmids. Plasmid pTAU4 encodes a mini-chromosome maintenance protein homolog and no RepA protein; the implications for DNA replication are considered. Plasmid pORA1 is the first Sulfolobus plasmid to be characterized that does not encode the otherwise highly conserved DNA-binding PlrA protein. Another encoded protein appears to be specific for the New Zealand plasmids. The three plasmids should provide useful model systems for functional studies of these important crenarchaeal proteins.

Amino Acid Motifs↗

PubMed2004

Morphology and genome organization of the virus PSV of the hyperthermophilic archaeal genera Pyrobaculum and Thermoproteus: a novel virus family, the Globuloviridae.

A novel virus, termed Pyrobaculum spherical virus (PSV), is described that infects anaerobic hyperthermophilic archaea of the genera Pyrobaculum and Thermoproteus. Spherical enveloped virions, about 100 nm in diameter, contain a major multimeric 33-kDa protein and host-derived lipids. A viral envelope encases a superhelical nucleoprotein core containing linear double-stranded DNA. The PSV infection cycle does not cause lysis of host cells. The viral genome was sequenced and contains 28337 bp. The genome is unique for known archaeal viruses in that none of the genes, including that encoding the major structural protein, show any significant sequence matches to genes in public sequence databases. Exceptionally for an archaeal double-stranded DNA virus, almost all the recognizable genes are located on one DNA strand. The ends of the genome consist of 190-bp inverted repeats that contain multiple copies of short direct repeats. The two DNA strands are probably covalently linked at their termini. On the basis of the unusual morphological and genomic properties of this DNA virus, we propose to assign PSV to a new viral family, the Globuloviridae.

Archaeal Viruses↗

PubMed2004

Genomic comparison of archaeal conjugative plasmids from Sulfolobus.

All of the known self-transmissable plasmids of the Archaea have been found in the genus Sulfolobus. To gain more insight into archaeal conjugative processes, four newly isolated self-transmissable plasmids, pKEF9, pHVE14, pARN3 and pARN4, were sequenced and subjected to a comparative sequence analysis with two earlier sequenced plasmids, pNOB8 and pING1. The analyses revealed three conserved and functionally distinct sections in the genomes. Section A is considered to encode the main components of the conjugative apparatus, where two genes show low but significant sequence similarity to sections of genes encoding bacterial conjugative proteins. A putative origin of replication is located in section B, which is highly conserved in sequence and contains several perfect and imperfect direct and inverted repeats. Further downstream, in section C, an operon encoding six to nine smaller proteins is implicated in the initiation and regulation of replication. Each plasmid carries an integrase gene of the type that does not partition on integration, and there is strong evidence for their integration into host chromosomes, where they may facilitate intercellular exchange of chromosomal genes. Two plasmids contain hexameric short regularly spaced repeats (SRSR), which have been implicated in plasmid maintenance, and each plasmid carries multiple recombination motifs, concentrated in the variable regions, which likely provide sites for genomic rearrangements.

Base Sequence↗

PubMed2003

MUTAGEN: multi-user tool for annotating genomes.

SUMMARY: MUTAGEN is a free prokaryotic annotation system. It offers the advantages of genome comparison, graphical sequence browsers, search facilities and open-source for user-specific adjustments. The web-interface allows several users to access the system from standard desktop computers. The Sulfolobus acidocaldarius genome, and several plasmids and viruses have so far been analysed and annotated using MUTAGEN. AVAILABILITY: MUTAGEN is released as open-source software under GPL. The code is available for download and/or contribution at http://dac.molbio.ku.dk/bioinformatics/MUTAGEN/

Database Management Systems↗

PubMed2003

Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes.

Short regularly spaced repeats (SRSRs) occur in multiple large clusters in archaeal chromosomes and as smaller clusters in some archaeal conjugative plasmids and bacterial chromosomes. The sequence, size, and spacing of the repeats are generally constant within a cluster but vary between clusters. For the crenarchaeon Sulfolobus solfataricus P2, the repeats in the genome fall mainly into two closely related sequence families that are arranged in seven clusters containing a total of 441 repeats which constitute ca. 1% of the genome. The Sulfolobus conjugative plasmid pNOB8 contains a small cluster of six repeats that are identical in sequence to one of the repeat variants in the S. solfataricus chromosome. Repeats from the pNOB8 cluster were amplified and tested for protein binding with cell extracts from S. solfataricus. A 17.5-kDa SRSR-binding protein was purified from the cell extracts and sequenced. The protein is N terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also recognizes both main families of repeat sequences in S. solfataricus. The recombinant protein, expressed in Escherichia coli, showed the same binding properties to the SRSR repeat as the native one. The SSO454 protein exhibits a tripartite internal repeat structure which yields a good sequence match with a helix-turn-helix DNA-binding motif. Although this putative motif is shared by other archaeal proteins, orthologs of SSO454 were only detected in species within the Sulfolobus genus and in the closely related Acidianus genus. We infer that the genus-specific protein induces an opening of the structure at the center of each DNA repeat and thereby produces a binding site for another protein, possibly a more conserved one, in a process that may be essential for higher-order stucturing of the SRSR clusters.

Amino Acid Sequence↗

PubMed2002

Mobile elements in archaeal genomes.

The recent availability of several archaeal genome sequences has provided a basis for detailed analyses of the frequency, location and phylogeny of archaeal mobile elements. All the known elements fall into two main types, autonomous insertion sequence (IS) elements and the non-autonomous miniature inverted repeat element (MITE)-like elements. Both classes are considered to be mobilized via transposases that are encoded by the IS elements, although mobility has only been demonstrated experimentally for a few elements. The number, and diversity, of the elements differs greatly between the genomes. At one extreme Sulfolobus solfataricus P2 and Halobacterium NRC-1 are very rich in elements while Methanobacterium thermoautotrophicum contains none. The former also show examples of complex clusters of interwoven elements. An analysis of the genomic distribution in S. solfataricus suggests that the putative oriC and terC regions act as barriers for the mobility of both IS and MITE-like elements. Moreover, the very high level of truncated IS elements in the genomes of S. solfataricus, Sulfolobus tokodaii and Thermoplasma volcanium suggests that there may be a cellular mechanism for selectively inactivating IS elements at a point when they become too numerous and disadvantageous for the cell. Phylogenetically, archaeal IS elements are confined to 11 of the 17 known families of bacterial and eukaryal IS elements where some generate distinct subgroups. Finally, DNA viruses, plasmids and DNA fragments can also be inserted into, and excised from, archaeal genomes by means of an integrase-mediated mechanism that has special archaeal characteristics.

Crenarchaeota↗

PubMedDate not supplied

Archaeal integrative genetic elements and their impact on genome evolution.

Integrases encoded in archaeal genomes can be classified into seven families on the basis of their sequences. They constitute a super-family of tyrosine DNA recombinases together with a number of bacterial integrases and they are likely to be responsible for the formation of integrated elements in archaeal chromosomes. An integrated element is defined as possessing an integrase, a block of foreign genes, and a direct repeat at the two ends with one repeat unit overlapping a tRNA gene. There are two types of archaeal integrated elements, the SSV viral type, including those that carry the partitioned integrase gene, intN and intC, and the pNOB8 type, including those with a tRNA gene overlapping the attL site 5' prior to an integrase gene. Both known and unknown genes are present in these integrated elements and their encoded proteins may have facilitated the adaptation of archaea during evolution.

Chromosomes, Archaeal↗