Heritable integration of kDNA minicircle sequences from Trypanosoma cruzi into the avian genome: insights into human Chagas disease

We demonstrate the genetic transfer of DNA between eukaryotes from different kingdoms. The mitochondrial kinetoplast DNA (kDNA) of the intracellular parasite Trypanosoma cruzi is transferred to human patients with Chagas disease. This transfer was reproduced experimentally in rabbits and chickens. T...

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Bibliographic Details
Published in:Cell 2004-07, Vol.118 (2), p.175-186
Main Authors: Nitz, Nadjar, Gomes, Clever, de Cássia Rosa, Ana, D'Souza-Ault, Marian R, Moreno, Francisco, Lauria-Pires, Liana, Nascimento, Rubens J, Teixeira, Antonio R L
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Autoimmune Diseases - genetics
Autoimmune Diseases - immunology
Chagas Disease - genetics
Chagas Disease - immunology
Chick Embryo
Chickens - genetics
DNA, Kinetoplast - genetics
Gene Transfer, Horizontal - genetics
Genome
Genome, Human
Germ-Line Mutation - genetics
Globins - genetics
Humans
Long Interspersed Nucleotide Elements - genetics
Molecular Sequence Data
Pluripotent Stem Cells - metabolism
Rabbits
Recombination, Genetic - genetics
Retroelements - genetics
Trypanosoma cruzi
Trypanosoma cruzi - genetics
Trypanosoma cruzi - immunology
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Summary:We demonstrate the genetic transfer of DNA between eukaryotes from different kingdoms. The mitochondrial kinetoplast DNA (kDNA) of the intracellular parasite Trypanosoma cruzi is transferred to human patients with Chagas disease. This transfer was reproduced experimentally in rabbits and chickens. The kDNA is integrated into the host genome. In the human chromosomes, five loci were identified as integration sites, and the beta-globin locus and LINE-1 retrotransposons were frequently targeted. Short repeated sequences in the parasite and the target host DNAs favor kDNA integration by homologous recombination. Introduced kDNA was present in offspring of chronically infected rabbits and in chickens hatched from T. cruzi-inoculated eggs. kDNA incorporated into the chicken germline was inherited through the F2 generation in the absence of persistent infection. kDNA integration represents a potential cause for the autoimmune response that develops in a percentage of chronic Chagas patients, which can now be approached experimentally.
ISSN:0092-8674
DOI:10.1016/j.cell.2004.07.001