Journal Article•
Draft genome of the filarial nematode parasite Brugia malayi (Science (2007) (1756))
TL;DR: Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units.
Abstract: Parasitic nematodes that cause elephantiasis and river blindness threaten hundreds of millions of people in the developing world. We have sequenced the ∼90 megabase (Mb) genome of the human filarial parasite Brugia malayi and predict ∼11,500 protein coding genes in 71 Mb of robustly assembled sequence. Comparative analysis with the free-living, model nematode Caenorhabditis elegans revealed that, despite these genes having maintained little conservation of local synteny during ∼350 million years of evolution, they largely remain in linkage on chromosomal units. More than 100 conserved operons were identified. Analysis of the predicted proteome provides evidence for adaptations of B. malayi to niches in its human and vector hosts and insights into the molecular basis of a mutualistic relationship with its Wolbachia endosymbiont. These findings offer a foundation for rational drug design.
Citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: New insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies, which should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
Abstract: Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
1,370 citations
Centre national de la recherche scientifique1, Institut national de la recherche agronomique2, University of Évry Val d'Essonne3, University of Dundee4, University of Provence5, University of Rennes6, Woods Hole Oceanographic Institution7, North Carolina State University8, Iowa State University9, École normale supérieure de Lyon10, Queen's University Belfast11, University of Bari12, Swiss Institute of Bioinformatics13, University of Lausanne14, Wageningen University and Research Centre15, University of Edinburgh16, French Institute of Health and Medical Research17
TL;DR: The draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, is reported, providing insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.
Abstract: Plant-parasitic nematodes are major agricultural pests worldwide and novel approaches to control them are sorely needed. We report the draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, including tomato, cotton and coffee. Most of the assembled sequence of this asexually reproducing nematode, totaling 86 Mb, exists in pairs of homologous but divergent segments. This suggests that ancient allelic regions in M. incognita are evolving toward effective haploidy, permitting new mechanisms of adaptation. The number and diversity of plant cell wall-degrading enzymes in M. incognita is unprecedented in any animal for which a genome sequence is available, and may derive from multiple horizontal gene transfers from bacterial sources. Our results provide insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.
1,057 citations
Cites background from "Draft genome of the filarial nemato..."
...1 online), as shown by the substantial differences between their genome sequences and that of the human parasite Brugia malayi...
[...]
Wellcome Trust Sanger Institute1, Broad Institute2, J. Craig Venter Institute3, University of Texas Health Science Center at San Antonio4, University of York5, University of Maryland, College Park6, University of California, San Francisco7, Oswaldo Cruz Foundation8, University of Texas at San Antonio9, Universidade Federal de Minas Gerais10, University College Cork11, Iowa State University12, University of São Paulo13, University of Pittsburgh14, Kyoto University15, University of Southampton16, Natural History Museum17, Lille University of Science and Technology18, John Innes Centre19, Leiden University20, University of Göttingen21, University of Maryland, Baltimore22, Rush University Medical Center23, Illinois State University24, University at Buffalo25
TL;DR: Analysis of the 363 megabase nuclear genome of the blood fluke, the first sequenced flatworm, and a representative of the Lophotrochozoa offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and theDevelopment of tissues into organs.
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.
997 citations
TL;DR: It is shown that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts, potentially providing a mechanism for acquisition of new genes and functions.
Abstract: Although common among bacteria, lateral gene transfer-the movement of genes between distantly related organisms-is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as Wolbachia pipientis, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from Wolbachia bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire Wolbachia genome (>1 megabase) to short (<500 base pairs) insertions. Potential Wolbachia-to-host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted Wolbachia genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.
772 citations
References
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: A large fraction of the Caenorhabditis elegans interactome network is mapped, starting with a subset of metazoan-specific proteins, and more than 4000 interactions were identified from high-throughput, yeast two-hybrid screens.
Abstract: To initiate studies on how protein-protein interaction (or "interactome") networks relate to multicellular functions, we have mapped a large fraction of the Caenorhabditis elegans interactome network. Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. Independent coaffinity purification assays experimentally validated the overall quality of this Y2H data set. Together with already described Y2H interactions and interologs predicted in silico, the current version of the Worm Interactome (WI5) map contains approximately 5500 interactions. Topological and biological features of this interactome network, as well as its integration with phenome and transcriptome data sets, lead to numerous biological hypotheses.
1,733 citations
TL;DR: New insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies, which should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
Abstract: Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.
1,370 citations
Institut national de la recherche agronomique1, Centre national de la recherche scientifique2, University of Évry Val d'Essonne3, University of Dundee4, University of Provence5, University of Rennes6, Woods Hole Oceanographic Institution7, North Carolina State University8, Iowa State University9, École normale supérieure de Lyon10, Queen's University Belfast11, University of Bari12, University of Lausanne13, Swiss Institute of Bioinformatics14, Wageningen University and Research Centre15, University of Edinburgh16, French Institute of Health and Medical Research17
TL;DR: The draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, is reported, providing insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.
Abstract: Plant-parasitic nematodes are major agricultural pests worldwide and novel approaches to control them are sorely needed. We report the draft genome sequence of the root-knot nematode Meloidogyne incognita, a biotrophic parasite of many crops, including tomato, cotton and coffee. Most of the assembled sequence of this asexually reproducing nematode, totaling 86 Mb, exists in pairs of homologous but divergent segments. This suggests that ancient allelic regions in M. incognita are evolving toward effective haploidy, permitting new mechanisms of adaptation. The number and diversity of plant cell wall-degrading enzymes in M. incognita is unprecedented in any animal for which a genome sequence is available, and may derive from multiple horizontal gene transfers from bacterial sources. Our results provide insights into the adaptations required by metazoans to successfully parasitize immunocompetent plants, and open the way for discovering new antiparasitic strategies.
1,057 citations
Wellcome Trust Sanger Institute1, J. Craig Venter Institute2, Broad Institute3, University of Texas Health Science Center at San Antonio4, University of York5, University of Maryland, College Park6, University of California, San Francisco7, Oswaldo Cruz Foundation8, University of Texas at San Antonio9, Universidade Federal de Minas Gerais10, University College Cork11, Iowa State University12, University of São Paulo13, University of Pittsburgh14, Kyoto University15, University of Southampton16, Natural History Museum17, Lille University of Science and Technology18, John Innes Centre19, Leiden University20, University of Göttingen21, University of Maryland, Baltimore22, Illinois State University23, Rush University Medical Center24, University at Buffalo25
TL;DR: Analysis of the 363 megabase nuclear genome of the blood fluke, the first sequenced flatworm, and a representative of the Lophotrochozoa offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and theDevelopment of tissues into organs.
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.
997 citations