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Mechanism of genetic exchange in American trypanosomes

Nature volume 421, pages 936–939 (2003)Cite this article

Abstract

The kinetoplastid Protozoa are responsible for devastating diseases1. In the Americas, Trypanosoma cruzi is the agent of Chagas' disease—a widespread disease transmissible from animals to humans (zoonosis)—which is transmitted by exposure to infected faeces of blood-sucking triatomine bugs2. The presence of genetic exchange in T. cruzi and in Leishmania is much debated3,4. Here, by producing hybrid clones, we show that T. cruzi has an extant capacity for genetic exchange. The mechanism is unusual and distinct from that proposed for the African trypanosome, Trypanosoma brucei5. Two biological clones6 of T. cruzi were transfected to carry different drug-resistance markers7,8, and were passaged together through the entire life cycle. Six double-drug-resistant progeny clones, recovered from the mammalian stage of the life cycle, show fusion of parental genotypes, loss of alleles, homologous recombination, and uniparental inheritance of kinetoplast maxicircle DNA. There are strong genetic parallels between these experimental hybrids and the genotypes among natural isolates of T. cruzi. In this instance, aneuploidy through nuclear hybridization results in recombination across far greater genetic distances than mendelian genetic exchange. This mechanism also parallels genome duplication9,10.

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Figure 1: Hybrids of parental phenotypes and genotypes in experimentally derived double-drug-resistant biological clones of T. cruzi.
Figure 2: Phylogenetic support in GPI demonstrated by the incongruence between phylogenies for T. cruzi IIb (TCIIb; plus d and e) and TCIIc (plus d and e) lineages for putative recombinants, where a circled isolate indicates a putative recombinant and a boxed isolate indicates that parents were used for maximum likelihood breakpoint analysis.
Figure 3: Phylogenetic support for mosaic gene, or split gene, structures in putative recombinant ‘progeny’ between parental TCIIb and TCIIc (gpi locus), and parental TCIIc and TCI (tcp locus) using bootscan analysis.

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References

  1. Cook, G. C. & Zumla, A. (eds) Manson's Tropical Diseases (Saunders, London, 2003)

  2. World Health Organisation. Control of Chagas Disease (World Health Organisation Technical Report Series 905, Geneva, 2002)

    Google Scholar 

  3. Machado, C. A. & Ayala, F. J. Nucleotide sequences provide evidence of genetic exchange among distantly related lineages of Trypanosoma cruzi. Proc. Natl Acad. Sci. USA 98, 7396–7401 (2001)

    Article  ADS  CAS  Google Scholar 

  4. Gibson, W. C. & Stevens, J. R. Genetic exchange in the trypanosomatidae. Adv. Parasitol. 43, 1–46 (1999)

    Article  CAS  Google Scholar 

  5. Bingle, L. E., Eastlake, J. L., Bailey, M. & Gibson, W. C. A novel GFP approach for the analysis of genetic exchange in trypanosomes allowing the in situ detection of mating events. Microbiology 147, 3231–3240 (2001)

    Article  CAS  Google Scholar 

  6. Carrasco, H. J., Frame, I. A., Valente, S. A. & Miles, M. A. Genetic exchange as a possible source of genomic diversity in sylvatic populations of Trypanosoma cruzi. Am. J. Trop. Med. Hyg. 54, 418–424 (1996)

    Article  CAS  Google Scholar 

  7. Gibson, W. C. & Bailey, M. Genetic exchange in Trypanosoma brucei: evidence for meiosis from analysis of a cross between drug-resistant transformants. Mol. Biochem. Parasitol. 64, 241–252 (1996)

    Article  Google Scholar 

  8. Stothard, J. R., Frame, I. A. & Miles, M. A. Genetic diversity and genetic exchange in Trypanosoma cruzi: dual drug-resistant ‘progeny’ from episomal transformants. Mem. Inst. Oswaldo Cruz 94 Suppl. 1, 189–193 (1999)

    Article  Google Scholar 

  9. Ohno, S. Evolution by Gene Duplication (Springer, Berlin, 1970)

    Book  Google Scholar 

  10. Knight, J. All genomes great and small. Nature 417, 374–376 (2002)

    Article  ADS  CAS  Google Scholar 

  11. Brisse, S., Barnabe, C. & Tibayrenc, M. Identification of six Trypanosoma cruzi phylogenetic lineages by random amplified polymorphic DNA and multilocus enzyme electrophoresis. Int. J. Parasitol. 30, 35–44 (2000)

    Article  CAS  Google Scholar 

  12. Mendonca, M. B. et al. Two main clusters within Trypanosoma cruzi zymodeme 3 are defined by distinct regions of the ribosomal RNA cistron. Parasitology 124, 177–184 (2002)

    Article  CAS  Google Scholar 

  13. Oliveira, R. P. et al. Probing the genetic population structure of Trypanosoma cruzi with polymorphic microsatellites. Proc. Natl Acad. Sci. USA 95, 3776–3780 (1998)

    Article  ADS  CAS  Google Scholar 

  14. Miles, M. A. et al. Do radically dissimilar Trypanosoma cruzi strains (zymodemes) cause Venezuelan and Brazilian forms of Chagas disease? Lancet 1, 1338–1340 (1981)

    Article  CAS  Google Scholar 

  15. Gaunt, M. W. & Miles, M. A. The ecotopes and evolution of triatomine bugs (Triatominae) and their associated trypanosomes. Mem. Inst. Oswaldo Cruz 95, 557–565 (2000)

    Article  CAS  Google Scholar 

  16. Tibayrenc, M. & Ayala, F. J. The clonal theory of parasitic protozoa: 12 years on. Trends Parasitol. 18, 405–410 (2002)

    Article  CAS  Google Scholar 

  17. McDaniel, J. P. & Dvorak, J. A. Identification, isolation, and characterization of naturally-occurring Trypanosoma cruzi variants. Mol. Biochem. Parasitol. 57, 213–222 (1993)

    Article  CAS  Google Scholar 

  18. Kelly, J. M. Genetic transformation of parasitic protozoa. Adv. Parasitol. 39, 227–270 (1997)

    Article  CAS  Google Scholar 

  19. Wilkinson, S. R. et al. The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin. J. Biol. Chem. 277, 17062–17071 (2002)

    Article  CAS  Google Scholar 

  20. Robello, C., Gamarro, F., Castanys, S. & Alvarez-Valin, F. Evolutionary relationships in Trypanosoma cruzi: molecular phylogenetics supports the existence of a new major lineage of strains. Gene 246, 331–338 (2000)

    Article  CAS  Google Scholar 

  21. MacLeod, A. et al. Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures. Proc. Natl Acad. Sci. USA 97, 13442–13447 (2000)

    Article  ADS  CAS  Google Scholar 

  22. Spratt, B. G. & Maiden, M. C. J. Bacterial population genetics, evolution and epidemiology. Phil. Trans. R. Soc. Lond. B 354, 701–710 (1999)

    Article  CAS  Google Scholar 

  23. Chamnanpunt, J., Shan, W. X. & Tyler, B. M. High frequency mitotic gene conversion in genetic hybrids of the oomycete Phytophthora sojae. Proc. Natl Acad. Sci. USA 98, 14530–14535 (2001)

    Article  ADS  CAS  Google Scholar 

  24. Cruz, A. K., Titus, R. & Beverley, S. M. Plasticity in chromosome number and testing of essential genes in Leishmania by targeting. Proc. Natl Acad. Sci. USA 90, 1599–1603 (1993)

    Article  ADS  CAS  Google Scholar 

  25. Gaunt, M. W. & Miles, M. A. A molecular clock for the insects dates the origin of the insects and accords with paleontological and biogeographic landmarks. Mol. Biol. Evol. 19, 748–761 (2002)

    Article  CAS  Google Scholar 

  26. Miles, M. A. in Protocols in Molecular Parasitology (ed. Hyde, J. E.) 15–28 (Humana, Totowa, New Jersey, 1992)

    Google Scholar 

  27. Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. & Higgins, D. G. CLUSTAL _ X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 25, 4876–4882 (1997)

    Article  CAS  Google Scholar 

  28. Salminen, M. O., Carr, J. K., Burke, D. S. & McCutchan, F. E. Identification of breakpoints in intergenotypic recombinants of HIV type 1 by bootscanning. AIDS Res. Hum. Retro. 11, 1423–1425 (1995)

    Article  CAS  Google Scholar 

  29. Holmes, E. C., Worobey, M. & Rambaut, A. Phylogenetic evidence for recombination in dengue virus. Mol. Biol. Evol. 16, 405–409 (1999)

    Article  CAS  Google Scholar 

  30. Dopazo, J., Dress, A. & Vonhaeseler, A. Split decomposition—a technique to analyse viral evolution. Proc. Natl Acad. Sci. USA 90, 10320–10324 (1993)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Wellcome Trust for financial support, D. Conway for valuable advice, and S. Wilkinson, S. Obado and J. Kelly for gifts of primers and comments on the manuscript.

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Author notes

  1. Nidia Acosta & Antonieta Rojas de Arias

    Present address: Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Asuncion, Paraguay

  2. Iain A. Frame

    Present address: The Wellcome Trust, 183 Euston Road, London, NW1 2BE, UK

  3. J. Russell Stothard

    Present address: Department of Infectious Disease Epidemiology, Imperial College, London, W2 1PG, UK

Authors and Affiliations

  1. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, WC1E 7HT, London, UK

    Michael W. Gaunt, Matthew Yeo, Iain A. Frame, Martin C. Taylor, Susana Solis Mena, Paul Veazey, Graham A. J. Miles & Michael A. Miles

  2. Department of Zoology, The Natural History Museum, Cromwell Road, SW7 5BD, London, UK

    J. Russell Stothard

  3. Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela

    Hernan J. Carrasco

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Correspondence to Michael A. Miles.

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Gaunt, M., Yeo, M., Frame, I. et al. Mechanism of genetic exchange in American trypanosomes. Nature 421, 936–939 (2003). https://doi.org/10.1038/nature01438

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