The genomes of four tapeworm species reveal adaptations to parasitism

Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis , E. granulosus, Taenia solium and the laboratory model Hymeno...

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Published inNature (London) Vol. 496; no. 7443; pp. 57 - 63
Main Authors Tsai, Isheng J., Zarowiecki, Magdalena, Holroyd, Nancy, Garciarrubio, Alejandro, Sanchez-Flores, Alejandro, Brooks, Karen L., Tracey, Alan, Bobes, Raúl J., Fragoso, Gladis, Sciutto, Edda, Aslett, Martin, Beasley, Helen, Bennett, Hayley M., Cai, Jianping, Camicia, Federico, Clark, Richard, Cucher, Marcela, De Silva, Nishadi, Day, Tim A., Deplazes, Peter, Estrada, Karel, Fernández, Cecilia, Holland, Peter W. H., Hou, Junling, Hu, Songnian, Huckvale, Thomas, Hung, Stacy S., Kamenetzky, Laura, Keane, Jacqueline A., Kiss, Ferenc, Koziol, Uriel, Lambert, Olivia, Liu, Kan, Luo, Xuenong, Luo, Yingfeng, Macchiaroli, Natalia, Nichol, Sarah, Paps, Jordi, Parkinson, John, Pouchkina-Stantcheva, Natasha, Riddiford, Nick, Rosenzvit, Mara, Salinas, Gustavo, Wasmuth, James D., Zamanian, Mostafa, Zheng, Yadong, Cai, Xuepeng, Soberón, Xavier, Olson, Peter D., Laclette, Juan P., Brehm, Klaus, Berriman, Matthew
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 04.04.2013
Nature Publishing Group
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Summary:Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis , E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control. Genome sequences of human-infective tapeworm species reveal extreme losses of genes and pathways that are ubiquitous in other animals, species-specific expansions of non-canonical heat shock proteins and families of known antigens, specialized detoxification pathways, and metabolism that relies on host nutrients; this information is used to identify new potential drug targets. Four tapeworm genomes sequenced Tapeworms cause echinococcosis and cysticercosis, two of the most severe parasitic diseases found in humans, and both on the World Health Organization's list of neglected tropical diseases. The publication of four tapeworm genome sequences — human-infective tapeworm species Echinococcus multilocularis , E. granulosus , Taenia solium and the laboratory model Hymenolepis microstoma — and identification of potential new drug targets for treating tapeworm infections is therefore a welcome development. Analysis of the sequences provides insights into the evolution of parasitism and reveals extreme losses of genes and pathways ubiquitous in other animals on one hand and species-specific expansions of genes on the other. More than a thousand E. multilocularis proteins emerge as potential targets, and of these, close to 200 with the highest scores may be targeted with existing pharmaceuticals.
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Wrote the manuscript: I.J.T., Ma.Z., N.H., M.B. Project conception and design: M.B., K.B., J.P.L., X.S., X.P.C. Project coordination: N.H., M.B, Ma.Z. Parasite material and nucleic acid preparation: R.J.B., P.D., C.F., T.H., J.L.H., K.L., X.N.L., S.N.H., N.M., P.D.O., M.R., E.S., N.P.S., Y.Z., K.B. Genome assembly: I.J.T., Ma.Z., A.G., K.E., A.S.F. Genome assembly improvement: I.J.T., K.L.B., A.T., H.B., S.N., T.H., A.G., K.E. Gene predictions: I.J.T., Ma.Z., A.S.F., X.S., K.L., J.L.H, A.G., K.E. Gene annotation: I.J.T., Ma.Z., K.L.B., A.T., H.B., O.L., S.N., R.C., R.J.B., G.F., E.S., X.S., J.P.L. K.L., J.L.H., A.G., K.E., S.N.H., X.P.C. Data processing, computational and bioinformatics support: N.D.S., M.A., J.A.K., K.E., J.L.H., S.N.H., X.S., Y.Z. Genome structure, comparative genomics & ploidy: I.J.T. Gene structure: A.S.F., I.J.T., Ma.Z. Experimental validation of micro-exons: T.H., H.M.B. Trans-splicing and polycistrons: A.G., K.B., F.K., I.J.T. Metabolism and detoxification: I.J.T., S.S.H., J.P., G.S., Ma.Z. Homeobox gene loss: P.W.H.H., J.Paps, N.R., P.D.O. Stem cell specialisations: K.B., I.J.T, Ma.Z. Domains: Ma.Z., J.D.W. Tapeworm specific genes and expansions: I.J.T., Ma.Z., C.F., G.S. Kinases and proteases: Ma.Z. GPCRs: T.A.D., Mo.Z. Neuropeptides: Mo.Z., T.A.D., U.K., K.B. Neuronal signalling: M.R., L.K., F.C., M.C. Drug targets: Ma.Z. Commented on the manuscript drafts: G.S., M.R., C.F., K.B., P.W.H.H., P.D.O., A.G., R.J.B., G.F., E.S., X.S., J.P.L., J.P.C.
Contributions
The Taenia solium Genome Consortium
Alejandro Garciarrubio1, Raúl J. Bobes2, Gladis Fragoso2, Alejandro Sánchez-Flores1, Karel Estrada1, Miguel A. Cevallos3, Enrique Morett1, Víctor González3, Tobias Portillo1, Adrian Ochoa-Leyva6, Marco José2, Edda Sciutto1, Abraham Landa4, Lucía Jiménez4, Víctor Valdés5, Julio C. Carrero2, Carlos Larralde2, Jorge Morales-Montor2, Jorge Limón-Lason2, Xavier Soberón1, 6 and Juan P. Laclette2
1 Institute of Biotechnology, 2Institute of Biomedical Research, 3Genomic Sciences Center, 4School of Medicine and 5School of Sciences, Universidad Nacional Autónoma de México; 04510 México D.F., 6National Institute of Genomic Medicine, Ministry of Health, 01900, México D.F., México.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature12031