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Letters to Nature

Nature 421, 936-939 (27 February 2003) | doi:10.1038/nature01438; Received 11 October 2002; Accepted 14 January 2003

Mechanism of genetic exchange in American trypanosomes

Michael W. Gaunt1, Matthew Yeo1, Iain A. Frame1,2, J. Russell Stothard2,3, Hernan J. Carrasco4, Martin C. Taylor1, Susana Solis Mena1, Paul Veazey1, Graham A. J. Miles1, Nidia Acosta5, Antonieta Rojas de Arias5 & Michael A. Miles1

  1. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
  2. Department of Zoology, The Natural History Museum, Cromwell Road, London SW7 5BD, UK
  3. Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
  4. Departamento de Medicina Tropical, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asuncion, Asuncion, Paraguay
  5. Present address: The Wellcome Trust, 183 Euston Road, London NW1 2BE, UK (I.A.F.); Department of Infectious Disease Epidemiology, Imperial College, London W2 1PG, UK (J.R.S.).

Correspondence to: Michael A. Miles1 Correspondence and requests for materials should be addressed to M.A.M. (e-mail: Email: michael.miles@lshtm.ac.uk).

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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.