-
Matthew Berriman,
Brian J Haas,
Philip T LoVerde,
R Alan Wilson,
Gary P Dillon,
Gustavo C Cerqueira,
Susan T Mashiyama,
Bissan Al-Lazikani,
Luiza F Andrade,
Peter D Ashton, [......],
Adrian R Tivey,
Owen White,
David L Williams,
Jennifer Wortman,
Wenjie Wu,
Mostafa Zamanian,
Adhemar Zerlotini,
Claire M Fraser-Liggett, Barclay G Barrell,
Najib M El-Sayed
[show abstract]
[hide abstract]
ABSTRACT: Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
Nature 08/2009; 460(7253):352-8. · 36.28 Impact Factor
-
Matthew T G Holden,
Heidi Hauser,
Mandy Sanders,
Thi Hoa Ngo,
Inna Cherevach,
Ann Cronin,
Ian Goodhead,
Karen Mungall,
Michael A Quail,
Claire Price, [......],
Josh D Slater,
Hilde E Smith,
Brian G Spratt,
Jianguo Xu,
Changyun Ye,
Stephen Bentley, Barclay G Barrell,
Constance Schultsz,
Duncan J Maskell,
Julian Parkhill
[show abstract]
[hide abstract]
ABSTRACT: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly understood.
The sequencing of whole genomes of S. suis isolates provides opportunities to investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for which genome sequences are currently available. Accordingly, approximately 40% of the approximately 2 Mb genome is unique in comparison to other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation; virtually all of the genome is common to the S. suis strains. The only exceptions are three approximately 90 kb regions, present in the two isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in putative virulence and colonization factors.
The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has contributed to the evolution of drug resistance.
PLoS ONE 02/2009; 4(7):e6072. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Artemis and Artemis Comparison Tool (ACT) have become mainstream tools for viewing and annotating sequence data, particularly for microbial genomes. Since its first release, Artemis has been continuously developed and supported with additional functionality for editing and analysing sequences based on feedback from an active user community of laboratory biologists and professional annotators. Nevertheless, its utility has been somewhat restricted by its limitation to reading and writing from flat files. Therefore, a new version of Artemis has been developed, which reads from and writes to a relational database schema, and allows users to annotate more complex, often large and fragmented, genome sequences.
Artemis and ACT have now been extended to read and write directly to the Generic Model Organism Database (GMOD, http://www.gmod.org) Chado relational database schema. In addition, a Gene Builder tool has been developed to provide structured forms and tables to edit coordinates of gene models and edit functional annotation, based on standard ontologies, controlled vocabularies and free text.
Artemis and ACT are freely available (under a GPL licence) for download (for MacOSX, UNIX and Windows) at the Wellcome Trust Sanger Institute web sites: http://www.sanger.ac.uk/Software/Artemis/ http://www.sanger.ac.uk/Software/ACT/
Bioinformatics 11/2008; 24(23):2672-6. · 5.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Artemis Comparison Tool (ACT) allows an interactive visualisation of comparisons between complete genome sequences and associated annotations. The comparison data can be generated with several different programs; BLASTN, TBLASTX or Mummer comparisons between genomic DNA sequences, or orthologue tables generated by reciprocal FASTA comparison between protein sets. It is possible to identify regions of similarity, insertions and rearrangements at any level from the whole genome to base-pair differences. ACT uses Artemis components to display the sequences and so inherits powerful searching and analysis tools. ACT is part of the Artemis distribution and is similarly open source, written in Java and can run on any Java enabled platform, including UNIX, Macintosh and Windows.
Bioinformatics 09/2005; 21(16):3422-3. · 5.47 Impact Factor
-
Scott P Keely,
Hubert Renauld,
Ann E Wakefield,
Melanie T Cushion,
A George Smulian,
Nigel Fosker,
Audrey Fraser,
David Harris,
Lee Murphy,
Claire Price,
Michael A Quail,
Kathy Seeger,
Sarah Sharp,
Carolyn J Tindal,
Tim Warren,
Eduard Zuiderwijk, Barclay G Barrell,
James R Stringer,
Neil Hall
[show abstract]
[hide abstract]
ABSTRACT: In the fungus Pneumocystis carinii, at least three gene families (PRT1, MSR, and MSG) have the potential to generate high-frequency antigenic variation, which is likely to be a strategy by which this parasitic fungus is able to prolong its survival in the rat lung. Members of these gene families are clustered at chromosome termini, a location that fosters recombination, which has been implicated in selective expression of MSG genes. To gain insight into the architecture, evolution, and regulation of these gene clusters, six telomeric segments of the genome were sequenced. Each of the segments began with one or more unique genes, after which were members of different gene families, arranged in a head-to-tail array. The three-gene repeat PRT1-MSR-MSG was common, suggesting that duplications of these repeats have contributed to expansion of all three families. However, members of a gene family in an array were no more similar to one another than to members in other arrays, indicating rapid divergence after duplication. The intergenic spacers were more conserved than the genes and contained sequence motifs also present in subtelomeres, which in other species have been implicated in gene expression and recombination. Long mononucleotide tracts were present in some MSR genes. These unstable sequences can be expected to suffer frequent frameshift mutations, providing P. carinii with another mechanism to generate antigen variation.
Genetics 09/2005; 170(4):1589-600. · 4.01 Impact Factor
-
Matthew Berriman,
Elodie Ghedin,
Christiane Hertz-Fowler,
Gaëlle Blandin,
Hubert Renauld,
Daniella C Bartholomeu,
Nicola J Lennard,
Elisabet Caler,
Nancy E Hamlin,
Brian Haas, [......],
Elisabetta Ullu,
J David Barry,
Alan H Fairlamb,
Fred Opperdoes, Barclay G Barrell,
John E Donelson,
Neil Hall,
Claire M Fraser,
Sara E Melville,
Najib M El-Sayed
[show abstract]
[hide abstract]
ABSTRACT: African trypanosomes cause human sleeping sickness and livestock trypanosomiasis in sub-Saharan Africa. We present the sequence and analysis of the 11 megabase-sized chromosomes of Trypanosoma brucei. The 26-megabase genome contains 9068 predicted genes, including approximately 900 pseudogenes and approximately 1700 T. brucei-specific genes. Large subtelomeric arrays contain an archive of 806 variant surface glycoprotein (VSG) genes used by the parasite to evade the mammalian immune system. Most VSG genes are pseudogenes, which may be used to generate expressed mosaic genes by ectopic recombination. Comparisons of the cytoskeleton and endocytic trafficking systems with those of humans and other eukaryotic organisms reveal major differences. A comparison of metabolic pathways encoded by the genomes of T. brucei, T. cruzi, and Leishmania major reveals the least overall metabolic capability in T. brucei and the greatest in L. major. Horizontal transfer of genes of bacterial origin has contributed to some of the metabolic differences in these parasites, and a number of novel potential drug targets have been identified.
Science 08/2005; 309(5733):416-22. · 31.20 Impact Factor
-
Stephen J Aves,
Cherryl Hunt,
Zheng Xiang,
Michael H Lyne,
Valerie Wood,
Marie-Adèle Rajandream,
Jason Skelton,
Carol M Churcher,
Timothy Warren,
David Harris,
Rhian Gwilliam, Barclay G Barrell
[show abstract]
[hide abstract]
ABSTRACT: Expression of the mei3 gene is sufficient to induce meiosis in the fission yeast Schizosaccharomyces pombe. The mei3 gene is located 0.64 Mb from the telomere of the left arm of Sz. pombe chromosome II. We have sequenced and analysed 107 kb of DNA from the mei3 genomic region. The sequence includes 14 known genes (bag1-B, csh3, dps1, gpt1, mei3, mfm3, pac1, prp31, rpl38-1, rpn3, rti1, spa1, spm1 and ubc4) and 26 other open reading frames (ORFs) longer than 100 codons: a density of one protein-coding gene per 2.7 kb. Twenty-one of the 40 ORFs (53%) have introns. In addition there is one lone Tf1 transposon long terminal repeat (LTR), tRNA(Trp) and tRNA(Ser) genes and a 5S rRNA gene. 14 of the novel ORFs show sequence similarities which suggest functions of their products, including a coatomer alpha-subunit, a catechol O-methyltransferase, protein kinase, asparagine synthetase, zinc metalloprotease, acetyltransferase, phosphatidylinositol 4-kinase, inositol polyphosphate phosphatase, GTPase-activating protein, permease, pre-mRNA splicing factor, 20S proteasome component and a thioredoxin-like protein. One predicted protein has similarity to the human Cockayne syndrome protein CSA and one with human GTPase XPA binding protein XAB1. Three ORFs are likely to code for proteins because they have sequence similarity with hypothetical proteins, three encode predicted coiled-coil proteins and four are sequence orphans.
Yeast 05/2002; 19(6):521-7. · 1.89 Impact Factor
-
Zheng Xiang,
Karen Moore,
Valerie Wood,
Maire-Adèle Rajandream, Barclay G. Barrell,
Jason Skelton,
Carol M. Churcher,
Michael H. Lyne,
Karen Devlin,
Rhian Gwilliam,
Kim M. Rutherford,
Stephen J. Aves
[show abstract]
[hide abstract]
ABSTRACT: One hundred and fourteen kilobase pairs (kb) of contiguous genomic sequence have been determined immediately distal to the his5 genetic marker located about 0.9 Mb from the centromere on the long arm of Schizosaccharomyces pombe chromosome 2. The sequence is contained in overlapping cosmid clones c16H5, c12D12, c24C6 and c19G7, of which 20 kb are identical to previously reported sequence from clone c21H7. The remaining 93 781 bp of sequence contains 10 known genes (cdc14, cdm1, cps1, gpa1, msh2, pck2, rip1, rps30-2, sad1 and ubl1), 32 open reading frames (ORFs) capable of coding for proteins of at least 100 amino acid residues in length, one 5S rRNA gene, one tRNAPro gene, one lone Tf1-type long terminal repeat (LTR) and one lone Tf2-type LTR. There is a density of one protein-coding gene per 2.2 kb and 22 of the 42 ORFs (52%) incorporate one or more introns. Twenty-one of the novel ORFs show sequence similarities which suggest functions of their products, including a cyclin C, a MADS box transcription factor, mad2-like protein, telomere binding protein, topoisomerase II-associated protein, ATP-dependent DEAH box RNA helicase, G10 protein, ubiquitin-activating e1-like enzyme, nucleoporin, prolyl-tRNA synthetase, peptidylprolyl isomerase, δ-1-pyrroline-5-carboxylate dehydrogenase, protein transport protein, coatomer epsilon, TCP-1 chaperonin, β-subunit of 6-phosphofructokinase, aminodeoxychorismate lyase, a phosphate transport protein and a thioredoxin. The sequence has been submitted to the EMBL database under Accession Nos AL021839, AL022104, AL031786 and AL035085. Copyright © 2000 John Wiley & Sons, Ltd.
Yeast 10/2000; 16(15):1405 - 1411. · 1.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The sequence has been determined of 68 897 bp of genomic DNA including the expressed mat1 mating-type locus from Schizosaccharomyces pombe h−S strain 972. The DNA sequence, located on the long arm of fission yeast chromosome II and contained in two cosmid clones, was analysed to reveal one autonomously replicating sequence, two retrotransposon long terminal repeats (LTRs), one tRNAGly gene and 33 open reading frames (ORFs), of which 15 contain introns. Nine of these ORFs code for previously described genes (trt1, rpl10, rps21, nif1, sui1 (psu1), matMi, matMc, let1 and rpa4), one of which (trt1) contains 15 introns, the highest number yet recorded in a gene of S. pombe. Of the remaining 24 ORFs, sequence similarity suggests that the function of 13 of the encoded proteins may be predicted and these include four mitochondrial proteins, two transport proteins, two signalling molecules, a component of serine palmitolytransferase, a homologue of 3-methyladenine DNA glycosylase, a multifunctional alcohol dehydrogenase, a killer toxin sensitivity factor and an acetyl transferase. Six deduced sequences appear to be related to proteins of unknown function in Saccharomyces cerevisiae or S. pombe and the remaining five are hypothetical proteins. This sequence has been submitted to the EMBL database under the following entries: SPBC23G7 (Accession No. AL035065), SPBC18E5 (AL035077) and SPBC29A3 (part) (AL022299). Copyright © 2000 John Wiley & Sons, Ltd.
Yeast 07/2000; 16(11):1061 - 1067. · 1.89 Impact Factor
