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. 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.
Nitz
Nadjar
N
Chagas Disease Multidisciplinary Research Laboratory, Faculty of Medicine, University of Brasília, Brasília, Brazil.
Gomes
Clever
C
de Cássia Rosa
Ana
A
D'Souza-Ault
Marian R
MR
Moreno
Francisco
F
Lauria-Pires
Liana
L
Nascimento
Rubens J
RJ
Teixeira
Antonio R L
AR
D000818:Animals; D000831:Animals, Newborn; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D014355:Chagas Disease / Q000235:genetics* / Q000276:immunology; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D018105:DNA, Kinetoplast / Q000235:genetics*; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D016678:Genome; D015894:Genome, Human; D018095:Germ-Line Mutation / Q000235:genetics; D005914:Globins / Q000235:genetics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008969:Molecular Sequence Data; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011817:Rabbits; D011995:Recombination, Genetic / Q000235:genetics*; D018626:Retroelements / Q000235:genetics; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000276:immunology
D018105:DNA, Kinetoplast; D018626:Retroelements; D005914:Globins