Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni

Abstract

Schistosoma mansoni is the primary causative agent of schistosomiasis, which affects 200 million individuals in 74 countries. We generated 163,000 expressed-sequence tags (ESTs) from normalized cDNA libraries from six selected developmental stages of the parasite, resulting in 31,000 assembled sequences and 92% sampling of an estimated 14,000 gene complement. By analyzing automated Gene Ontology assignments, we provide a detailed view of important S. mansoni biological systems, including characterization of metazoa-specific and eukarya-conserved genes. Phylogenetic analysis suggests an early divergence from other metazoa. The data set provides insights into the molecular mechanisms of tissue organization, development, signaling, sexual dimorphism, host interactions and immune evasion and identifies novel proteins to be investigated as vaccine candidates and potential drug targets.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Gene Ontology classification and frequently encountered Pfam domains in SmAEs.
Figure 2: Category distribution of eukarya-conserved and metazoa-specific SmAEs.
Figure 3: Frequency of sequenced transcripts in life-cycle stages.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. World Health Organization. TDR Strategic Direction for Research: Schistosomiasis (World Health Organization, Geneve, 2002).

  2. King, C.L. Initiation and regulation of disease in schistosomiasis. in Schistosomiasis (ed. Mahmoud, A.A.F.) 213–264 (Imperial College Press, London, 2001).

    Book  Google Scholar 

  3. Doenhoff, M.J., Kusel, J.R., Coles, G.C. & Cioli, D. Resistance of Schistosoma mansoni to praziquantel: is there a problem? Trans. R. Soc. Trop. Med. Hyg. 96, 465–469 (2002).

    Article  CAS  Google Scholar 

  4. Dunne, D. & Mountford, A. Resistance to infection in humans and animal models. in Schistosomiasis (ed. Mahmoud, A.A.F.) 133–211 (Imperial College Press, London, 2001).

    Chapter  Google Scholar 

  5. Coulson, P.S. The radiation-attenuated vaccine against schistosomes in animal models: paradigm for a human vaccine? Adv. Parasitol. 39, 271–336 (1997).

    Article  CAS  Google Scholar 

  6. Hausdorf, B. Early evolution of the bilateria. Syst. Biol. 49, 130–142 (2000).

    Article  CAS  Google Scholar 

  7. Simpson, A.J., Sher, A. & McCutchan, T.F. The genome of Schistosoma mansoni: isolation of DNA, its size, bases and repetitive sequences. Mol. Biochem. Parasitol. 6, 125–137 (1982).

    Article  CAS  Google Scholar 

  8. Santos, T.M. et al. Analysis of the gene expression profile of Schistosoma mansoni cercariae using the expressed sequence tag approach. Mol. Biochem. Parasitol. 103, 79–97 (1999).

    Article  CAS  Google Scholar 

  9. Williams, S.A. & Johnston, D.A. Helminth genome analysis: the current status of the filarial and schistosome genome projects. Filarial Genome Project. Schistosome Genome Project. Parasitology 118 Suppl, S19–S38 (1999).

  10. Soares, M.B. et al. Construction and characterization of a normalized cDNA library. Proc. Natl. Acad. Sci. USA 91, 9228–9232 (1994).

    Article  CAS  Google Scholar 

  11. Dias-Neto, E. et al. Minilibraries constructed from cDNA generated by arbitrarily primed RT–PCR: an alternative to normalized libraries for the generation of ESTs from nanogram quantities of mRNA. Gene 186, 135–142 (1997).

    Article  CAS  Google Scholar 

  12. Dias-Neto, E. et al. Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. Proc. Natl. Acad. Sci. USA 97, 3491–3496 (2000).

    Article  Google Scholar 

  13. Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

    Article  Google Scholar 

  14. Dehal, P. et al. The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. Science 298, 2157–2167 (2002).

    Article  CAS  Google Scholar 

  15. The C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018 (1998).

  16. Manning, G., Whyte, D.B., Martinez, R., Hunter, T. & Sudarsanam, S. The protein kinase complement of the human genome. Science 298, 1912–1934 (2002).

    Article  CAS  Google Scholar 

  17. Osman, A., Niles, E.G. & LoVerde, P.T. Identification and characterization of a Smad2 homologue from Schistosoma mansoni, a transforming growth factor-β signal transducer. J. Biol. Chem. 276, 10072–10082 (2001).

    Article  CAS  Google Scholar 

  18. Pappas, P.W. Membrane transport in helminth parasites: a review. Exp. Parasitol. 37, 469–530 (1975).

    Article  CAS  Google Scholar 

  19. Skelly, P.J., Kim, J.W., Cunningham, J. & Shoemaker, C.B. Cloning, characterization, and functional expression of cDNAs encoding glucose transporter proteins from the human parasite Schistosoma mansoni. J. Biol. Chem. 269, 4247–4253 (1994).

    CAS  PubMed  Google Scholar 

  20. Racoosin, E.L., Davies, S.J. & Pearce, E.J. Caveolae-like structures in the surface membrane of Schistosoma mansoni. Mol. Biochem. Parasitol. 104, 285–297 (1999).

    Article  CAS  Google Scholar 

  21. Xu, X. & Caulfield, J.P. Characterization of human low density lipoprotein binding proteins on the surface of schistosomula of Schistosoma mansoni. Eur. J. Cell Biol. 57, 229–235 (1992).

    CAS  PubMed  Google Scholar 

  22. Mair, G.R., Maule, A.G., Day, T.A. & Halton, D.W. A confocal microscopical study of the musculature of adult Schistosoma mansoni. Parasitology 121, 163–170 (2000).

    Article  Google Scholar 

  23. Halton, D.W. & Gustafsson, M.K.S. Functional morphology of the platyhelminth nervous system. Parasitology 113, S47–S72 (1996).

    Article  Google Scholar 

  24. Dorsey, C.H., Cousin, C.E., Lewis, F.A. & Stirewalt, M.A. Ultrastructure of the Schistosoma mansoni cercaria. Micron 33, 279–323 (2002).

    Article  Google Scholar 

  25. Hoffmann, K.F., Davis, E.M., Fischer, E.R. & Wynn, T.A. The guanine protein coupled receptor rhodopsin is developmentally regulated in the free-living stages of Schistosoma mansoni. Mol. Biochem. Parasitol. 112, 113–123 (2001).

    Article  CAS  Google Scholar 

  26. Pax, R.A. & Bennett, J.L. Neurobiology of parasitic platyhelminths: possible solutions to the problems of correlating structure with function. Parasitology 102 Suppl, S31–S39 (1991).

  27. Smart, D. et al. Peptides related to the Diploptera punctata allatostatins in nonarthropod invertebrates: an immunocytochemical survey. J. Comp. Neurol. 347, 426–432 (1994).

    Article  CAS  Google Scholar 

  28. Pryor, S.C. & Elizee, R. Evidence of opiates and opioid neuropeptides and their immune effects in parasitic invertebrates representing three different phyla: Schistosoma mansoni, Theromyzon tessulatum, Trichinella spiralis. Acta Biol. Hung. 51, 331–341 (2000).

    CAS  PubMed  Google Scholar 

  29. de Mendonca, R.L., Escriva, H., Bouton, D., Laudet, V. & Pierce, R.J. Hormones and nuclear receptors in schistosome development. Parasitol. Today 16, 233–240 (2000).

    Article  CAS  Google Scholar 

  30. Saule, P. et al. Early variations of host thyroxine and interleukin-7 favor Schistosoma mansoni development. J. Parasitol. 88, 849–855 (2002).

    Article  CAS  Google Scholar 

  31. Snyder, S.D., Loker, E.S., Johnston, D.A. & Rollinson, D. The Schistosomatidae: Advances in Phylogenetics and Genomics. in The Interrelationships of Platyhelminthes (eds. Littlewood, D.T.J. & Bray, R.A.) 194–199 (Taylor and Francis, London, 2000).

    Google Scholar 

  32. Basch, P.F. Schistosoma mansoni: nucleic acid synthesis in immature females from single-sex infections, paired in vitro with intact males and male segments. Comp. Biochem. Physiol. B 90, 389–392 (1988).

    Article  CAS  Google Scholar 

  33. DeMarco, R., Kowaltowski, A.T., Mortara, R.A. & Verjovski-Almeida, S. Molecular characterization and immunolocalization of Schistosoma mansoni ATP-diphosphohydrolase. Biochem. Biophys. Res. Commun. 307, 831–838 (2003).

    Article  CAS  Google Scholar 

  34. Fulford, A.J., Butterworth, A.E., Ouma, J.H. & Sturrock, R.F. A statistical approach to schistosome population dynamics and estimation of the life-span of Schistosoma mansoni in man. Parasitology 110 (Pt 3), 307–316 (1995).

    Article  Google Scholar 

  35. Murphy, C.T. et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277–283 (2003).

    Article  CAS  Google Scholar 

  36. Hu, P. et al. Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability. Am. J. Physiol. Renal Physiol. 283, F1200–F1207 (2002).

    Article  CAS  Google Scholar 

  37. Skelly, P.J., Da'dara, A. & Harn, D.A. Suppression of cathepsin B expression in Schistosoma mansoni by RNA interference. Int. J. Parasitol. 33, 363–369 (2003).

    Article  CAS  Google Scholar 

  38. Boyle, J.P., Wu, X.J., Shoemaker, C.B. & Yoshino, T.P. Using RNA interference to manipulate endogenous gene expression in Schistosoma mansoni sporocysts. Mol. Biochem. Parasitol. 128, 205–215 (2003).

    Article  CAS  Google Scholar 

  39. Wilson, R.A. & Barnes, P.E. The formation and turnover of the membranocalyx on the tegument of Schistosoma mansoni. Parasitology 74, 61–71 (1977).

    Article  CAS  Google Scholar 

  40. Dissous, C. & Capron, A. Convergent evolution of tropomyosin epitopes. Parasitol. Today 11, 45–46 (1995).

    Article  CAS  Google Scholar 

  41. Ramos, C.R. et al. Gene structure and M20T polymorphism of the Schistosoma mansoni Sm14 fatty acid-binding protein. Molecular, functional, and immunoprotection analysis. J. Biol. Chem. 278, 12745–12751 (2003).

    Article  CAS  Google Scholar 

  42. van der Kleij, D. et al. A novel host-parasite lipid cross-talk. Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization. J. Biol. Chem. 277, 48122–48129 (2002).

    Article  CAS  Google Scholar 

  43. Cutts, L. & Wilson, R.A. Elimination of a primary schistosome infection from rats coincides with elevated IgE titres and mast cell degranulation. Parasite Immunol. 19, 91–102 (1997).

    Article  CAS  Google Scholar 

  44. Damonneville, M., Pierce, R.J., Verwaerde, C. & Capron, A. Allergens of Schistosoma mansoni. II. Fractionation and characterization of S. mansoni egg allergens. Int. Arch. Allergy Appl. Immunol. 73, 248–255 (1984).

    Article  CAS  Google Scholar 

  45. Salter, J.P. et al. Cercarial elastase is encoded by a functionally conserved gene family across multiple species of schistosomes. J. Biol. Chem. 277, 24618–24624 (2002).

    Article  CAS  Google Scholar 

  46. Mansour, T.E. Chemotherapeutic Targets in Parasites (Cambridge University Press, Cambridge, 2002).

    Book  Google Scholar 

  47. Fietto, J.L., DeMarco, R. & Verjovski-Almeida, S. Use of degenerate primers and touchdown PCR for construction of cDNA libraries. Biotechniques 32, 1404–1411 (2002).

    Article  CAS  Google Scholar 

  48. Paquola, A., Nishiyama, M. Jr., Reis, E.M., daSilva, A.M. & Verjovski-Almeida, S. ESTWeb: bioinformatics services for EST sequencing projects. Bioinformatics 19, 1587–1588 (2003).

    Article  CAS  Google Scholar 

  49. Huang, X. & Madan, A. CAP3: A DNA sequence assembly program. Genome Res. 9, 868–877 (1999).

    Article  CAS  Google Scholar 

  50. Stekel, D.J., Git, Y. & Falciani, F. The comparison of gene expression from multiple cDNA libraries. Genome Res. 10, 2055–2061 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

E.D.N. thanks Associação Beneficente Alzira Denise Hertzog da Silva for financial support, D. Rollinson for providing schistosome isolates from Africa and Lebanon and M.G. dos Reis and N. Lucena for providing isolates from northeast Brazil. This project was financed by Fundação de Amparo a Pesquisa do Estado de Sao Paulo and by the Brazilian Ministry of Science and Technology, Conselho Nacional de Desenvolvimento Científico e Tecnológico. The York schistosomiasis group received support from the Biology and Biotechnology Science Research Council, Wellcome Trust and the European Commission Research for Development Programme, Sector Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sergio Verjovski-Almeida.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verjovski-Almeida, S., DeMarco, R., Martins, E. et al. Transcriptome analysis of the acoelomate human parasite Schistosoma mansoni. Nat Genet 35, 148–157 (2003). https://doi.org/10.1038/ng1237

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/ng1237

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing