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Mechanism of genetic exchange in American trypanosomes

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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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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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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