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1. From genomes to vaccines via the proteome.

Author

Wilson RA, Curwen RS, Braschi S, Hall SL, Coulson PS, and Ashton PD

Subjects
Animals, Antigens, Helminth immunology, Chromatography, Liquid, Electrophoresis, Gel, Two-Dimensional, Humans, Mass Spectrometry, Schistosoma mansoni genetics, Schistosomiasis mansoni prevention & control, Vaccines immunology, Antigens, Helminth genetics, Genome, Proteomics, Schistosoma mansoni immunology, Schistosomiasis mansoni immunology, Vaccines genetics
Abstract

An effective vaccine against schistosomiasis mansoni would be a valuable control tool and the high levels of protection elicited in rodents and primates by radiation-attenuated cercariae provide proof of principle. A major obstacle to vaccine development is the difficulty of identifying the antigens that mediate protection, not least because of the size of the genome at 280Mb DNA encoding 14,000 to 20,000 genes. The technologies collectively called proteomics, including 2D electrophoresis, liquid chromatography and mass spectrometry, now permit any protein to be identified provided there is extensive DNA data, and preferably a genome sequence. Applied to soluble (cytosolic) proteins from schistosomes, proteomics reveals the great similarity in composition between life cycle stages, with several WHO vaccine candidates amongst the most abundant constituents. The proteomic approach has been successfully applied to identify the secretions used by cercaria to penetrate host skin, the gut secretions of adult worms and the proteins exposed on the tegument surface. Soluble proteins can also be separated by 2D electrophoresis before western blotting to identify the full range of antigenic targets present in a parasite preparation. The next step is to discover which target proteins represent the weak points in the worm's defences.

Published
2004
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2. Linking proteome and genome: how to identify parasite proteins.

Author

Ashton PD, Curwen RS, and Wilson RA

Subjects
Amino Acid Sequence, Animals, Brugia malayi genetics, Genome, Protozoan, Leishmania genetics, Mass Spectrometry methods, Molecular Sequence Data, Phosphopyruvate Hydratase chemistry, Plasmodium genetics, Schistosoma mansoni genetics, Genome, Helminth Proteins chemistry, Proteome, Protozoan Proteins chemistry
Abstract

Parasite genome projects are generating an avalanche of sequence data. If this resource is to be exploited effectively for drug and vaccine design, there is an urgent need to make the link between these DNA sequences and the functional proteins of the parasite, which they encode. Here, we seek to demystify the revolutionary advances in protein identification based on mass spectrometry.

Published
2001
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3. Genome sequence of the pea aphid Acyrthosiphon pisum

Author

Richards, S, Gibbs, RA, Gerardo, NM, Moran, N, Nakabachi, A, Stern, D, Tagu, D, Wilson, ACC, Muzny, D, Kovar, C, Cree, A, Chacko, J, Chandrabose, MN, Dao, MD, Dinh, HH, Gabisi, RA, Hines, S, Hume, J, Jhangian, SN, Joshi, V, Lewis, LR, Liu, Y-S, Lopez, J, Morgan, MB, Nguyen, NB, Okwuonu, GO, Ruiz, SJ, Santibanez, J, Wright, RA, Fowler, GR, Hitchens, ME, Lozado, RJ, Moen, C, Steffen, D, Warren, JT, Zhang, J, Nazareth, LV, Chavez, D, Davis, C, Lee, SL, Patel, BM, Pu, L-L, Bell, SN, Johnson, AJ, Vattathil, S, Jr, WRL, Shigenobu, S, Dang, PM, Morioka, M, Fukatsu, T, Kudo, T, Miyagishima, S-Y, Jiang, H, Worley, KC, Legeai, F, Gauthier, J-P, Collin, O, Zhang, L, Chen, H-C, Ermolaeva, O, Hlavina, W, Kapustin, Y, Kiryutin, B, Kitts, P, Maglott, D, Murphy, T, Pruitt, K, Sapojnikov, V, Souvorov, A, Thibaud-Nissen, F, Camara, F, Guigo, R, Stanke, M, Solovyev, V, Kosarev, P, Gilbert, D, Gabaldon, T, Huerta-Cepas, J, Marcet-Houben, M, Pignatelli, M, Moya, A, Rispe, C, Ollivier, M, Quesneville, H, Permal, E, Llorens, C, Futami, R, Hedges, D, Robertson, HM, Alioto, T, Mariotti, M, Nikoh, N, McCutcheon, JP, Burke, G, Kamins, A, Latorre, A, Moran, NA, Ashton, P, Calevro, F, Charles, H, Colella, S, Douglas, A, Jander, G, Jones, DH, Febvay, G, Kamphuis, LG, Kushlan, PF, Macdonald, S, Ramsey, J, Schwartz, J, Seah, S, Thomas, G, Vellozo, A, Cass, B, Degnan, P, Hurwitz, B, Leonardo, T, Koga, R, Altincicek, B, Anselme, C, Atamian, H, Barribeau, SM, de Vos, M, Duncan, EJ, Evans, J, Ghanim, M, Heddi, A, Kaloshian, I, Vincent-Monegat, C, Parker, BJ, Perez-Brocal, V, Rahbe, Y, Spragg, CJ, Tamames, J, Tamarit, D, Tamborindeguy, C, Vilcinskas, A, Bickel, RD, Brisson, JA, Butts, T, Chang, C-C, Christiaens, O, Davis, GK, Duncan, E, Ferrier, D, Iga, M, Janssen, R, Lu, H-L, McGregor, A, Miura, T, Smagghe, G, Smith, J, van der Zee, M, Velarde, R, Wilson, M, Dearden, P, Edwards, OR, Gordon, K, Hilgarth, RS, Jr, RSD, Srinivasan, D, Walsh, TK, Ishikawa, A, Jaubert-Possamai, S, Fenton, B, Huang, W, Rizk, G, Lavenier, D, Nicolas, J, Smadja, C, Zhou, J-J, Vieira, FG, He, X-L, Liu, R, Rozas, J, Field, LM, Ashton, PD, Campbell, P, Carolan, JC, Douglas, AE, Fitzroy, CIJ, Reardon, KT, Reeck, GR, Singh, K, Wilkinson, TL, Huybrechts, J, Abdel-latief, M, Robichon, A, Veenstra, JA, Hauser, F, Cazzamali, G, Schneider, M, Williamson, M, Stafflinger, E, Hansen, KK, Grimmelikhuijzen, CJP, Price, DRG, Caillaud, M, van Fleet, E, Ren, Q, Gatehouse, JA, Brault, V, Monsion, B, Diaz, J, Hunnicutt, L, Ju, H-J, Pechuan, X, Aguilar, J, Cortes, T, Ortiz-Rivas, B, Martinez-Torres, D, Dombrovsky, A, Dale, RP, Davies, TGE, Williamson, MS, Jones, A, Sattelle, D, Williamson, S, Wolstenholme, A, Cottret, L, Sagot, MF, Heckel, DG, Hunter, W, Consortium, IAG, Universitat de Barcelona, Princeton University, Biologie des organismes et des populations appliquées à la protection des plantes (BIO3P), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Biologie Fonctionnelle, Insectes et Interactions (BF2I), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Baylor College of Medicine (BCM), Baylor University, An algorithmic view on genomes, cells, and environments (BAMBOO), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), IAGC, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon, Eisen, Jonathan A., and Eisen, Jonathan A

Subjects
0106 biological sciences, TANDEM REPEATS, Genome, Insect, Gene Transfer, RRES175, Sequència genòmica, Faculty of Science\Computer Science, CPG METHYLATION, 01 natural sciences, Genome, Medical and Health Sciences, International Aphid Genomics Consortium, Biologiska vetenskaper, Biology (General), GENE-EXPRESSION, 2. Zero hunger, Genetics, 0303 health sciences, Aphid, Afídids, General Neuroscience, GENOME SEQUENCE, food and beverages, DROSOPHILA CIRCADIAN CLOCK, Biological Sciences, Genetics and Genomics/Microbial Evolution and Genomics, INSECTE, Genètica microbiana, puceron, APIS-MELLIFERA, General Agricultural and Biological Sciences, Infection, symbiose, Biotechnology, Research Article, VIRUS VECTORING, 175_Genetics, SYMBIOTIC BACTERIA, Gene Transfer, Horizontal, QH301-705.5, ACYRTHOSIPHON PISUM, Biology, HOLOMETABOLOUS INSECTS, HOST-PLANT, 010603 evolutionary biology, PEA APHID, INSECT-PLANT, PHENOTYPIC PLASTICITY, RAVAGEUR DES CULTURES, SOCIAL INSECT, General Biochemistry, Genetics and Molecular Biology, Horizontal, 03 medical and health sciences, Buchnera, Gene family, Life Science, Animals, Symbiosis, Gene, 030304 developmental biology, Whole genome sequencing, General Immunology and Microbiology, Annotation, Genome sequence, Agricultural and Veterinary Sciences, 175_Entomology, Genètica animal, Bacteriocyte, génome, gène, Human Genome, Biology and Life Sciences, 15. Life on land, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, REPETITIVE ELEMENTS, DNA-SEQUENCES, Acyrthosiphon pisum, Genome Sequence, Genetics and Genomics/Genome Projects, Aphids, PHEROMONE-BINDING, Insect, Developmental Biology, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

The genome of the pea aphid shows remarkable levels of gene duplication and equally remarkable gene absences that shed light on aspects of aphid biology, most especially its symbiosis with Buchnera., Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems., Author Summary Aphids are common pests of crops and ornamental plants. Facilitated by their ancient association with intracellular symbiotic bacteria that synthesize essential amino acids, aphids feed on phloem (sap). Exploitation of a diversity of long-lived woody and short-lived herbaceous hosts by many aphid species is a result of specializations that allow aphids to discover and exploit suitable host plants. Such specializations include production by a single genotype of multiple alternative phenotypes including asexual, sexual, winged, and unwinged forms. We have generated a draft genome sequence of the pea aphid, an aphid that is a model for the study of symbiosis, development, and host plant specialization. Some of the many highlights of our genome analysis include an expanded total gene set with remarkable levels of gene duplication, as well as aphid-lineage-specific gene losses. We find that the pea aphid genome contains all genes required for epigenetic regulation by methylation, that genes encoding the synthesis of a number of essential amino acids are distributed between the genomes of the pea aphid and its symbiont, Buchnera aphidicola, and that many genes encoding immune system components are absent. These genome data will form the basis for future aphid research and have already underpinned a variety of genome-wide approaches to understanding aphid biology.

Published
2010
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