RETRACTED: Heritable Integration of kDNA Minicircle Sequences from Trypanosoma cruzi into the Avian Genome: Insights into Human Chagas Disease

round amastigote form by binary fission in various tissues of the mammalian host. (reviewed in Teixeira [1987]). Research Laboratory American trypanosomiasis infections span an exten-Faculty of Medicine sive geographical area between 42ЊN in the United University of Brasília States to 43ЊS in Argentina. Human Chagas disease is Brasília considered the most significant parasitic disease in Brazil Latin America. It is estimated that 16–18 million people are infected by T. cruzi. As a consequence, approximately 50,000 deaths occur every year. The acute infec-Summary tion usually goes unrecognized and enters a chronic stage that persists throughout the host's life span. How-We demonstrate the genetic transfer of DNA between ever, roughly 30% of infected individuals eventually will eukaryotes from different kingdoms. The mitochondrial develop disease with an array of possible manifestations kinetoplast DNA (kDNA) of the intracellular parasite affecting the heart, the digestive tract, and/or the periph-Trypanosoma cruzi is transferred to human patients eral nervous system (Prata, 2001). with Chagas disease. This transfer was reproduced The mitochondrion of T. cruzi contains the largest experimentally in rabbits and chickens. The kDNA is amount of extranuclear genetic material of any eukary-integrated into the host genome. In the human chro-ote. This kinetoplast DNA (kDNA) contains a few dozen mosomes, five loci were identified as integration sites, maxicircles (23 kb) and several thousand minicircles (1.4 and the ␤-globin locus and LINE-1 retrotransposons kb) catenated into a large and complex network (Kling-were frequently targeted. Short repeated sequences beil et al., 2002), comprising 10%–15% of the total cell in the parasite and the target host DNAs favor kDNA DNA (Lukes et al. 2002). The maxicircles are the func-integration by homologous recombination. Introduced tional equivalent of our mitochondrial DNA but contain kDNA was present in offspring of chronically infected several genes that require substantial posttranscrip-rabbits and in chickens hatched from T. cruzi-inocu-tional modification by RNA editing (Estevez and Simp-lated eggs. kDNA incorporated into the chicken germline son, 1999). The minicircles encode the guide RNAs that was inherited through the F2 generation in the absence direct this process, contributing to the enormous con-of persistent infection. kDNA integration represents a tent and heterogeneity in the mitochondrial DNA compo-potential cause for the autoimmune response that de-nent of these organisms (Campbell et al., 2003). velops in a percentage of chronic Chagas patients, Perhaps the most important problem in the field of which can now be approached experimentally. Chagas disease research is determination of the …