Interspecies DNA transfer is a major biological process leading to the accumulation of mutations inherited by sexual reproduction among eukaryotes. Lateral DNA transfer events and their inheritance has been challenging to document. In this study we modified a thermal asymmetric interlaced PCR by using additional targeted primers, along with Southern blots, fluorescence techniques, and bioinformatics, to identify lateral DNA transfer events from parasite to host. Instances of naturally occurring human infections by Trypanosoma cruzi are documented, where mitochondrial minicircles integrated mainly into retrotransposable LINE-1 of various chromosomes. The founders of five families show minicircle integrations that were transferred vertically to their progeny. Microhomology end-joining of 6 to 22 AC-rich nucleotide repeats in the minicircles and host DNA mediates foreign DNA integration. Heterogeneous minicircle sequences were distributed randomly among families, with diversity increasing due to subsequent rearrangement of inserted fragments. Mosaic recombination and hitchhiking on retrotransposition events to different loci were more prevalent in germ line as compared to somatic cells. Potential new genes, pseudogenes, and knockouts were identified. A pathway of minicircle integration and maintenance in the host genome is suggested. Thus, infection by T. cruzi has the unexpected consequence of increasing human genetic diversity, and Chagas disease may be a fortuitous share of negative selection. This demonstration of contemporary transfer of eukaryotic DNA to the human genome and its subsequent inheritance by descendants introduces a significant change in the scientific concept of evolutionary biology and medicine.
BACKGROUND The Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease.OBJECTIVES A short-term longitudinal study was conducted to evaluate this hypothesis.METHODS The study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing.RESULTS Three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube.MAIN CONCLUSIONS T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised.
Chagas disease is the main cause of heart failure and sudden death in the Western Hemisphere. The literature of the last decades reported on the changing epidemiological profiles of Chagas disease, which now threats the human population in the cities. The exodus of the Latin America people to the Northern Hemisphere explains the growing concern in countries where the transmission of Trypanosoma cruzi was accidental or transferred from a mother to her offspring. Herein, we present the evidence of the possible acquisition of the T. cruzi infection by sex. The staggering demonstration of the transmission of the T. cruzi infections from males and females to naïve mates by intercourse introduces substantial changes in the surveillance of the Chagas disease. Notably, the sexual transmission of the T. cruzi introduces changes in the concepts of medical care, prevention and control; specifically, the risk for the vertical transfer of the parasiteinduced kDNA mutations, underpinning the genetically driven autoimmunity, inheritance, and pathogenesis associated with multifaceted clinical manifestations of Chagas disease with high
After the horizontal transference of kDNA minicircle sequences into the genome of chagasic mammals it was possible to show the heritage of the kDNA mutation into those rabbits breed. However, mammals are permissive to infection by T. cruzi, which may persist through the animal life. To ensure that the kDNA mutation was not only a noise produced by the cryptic infection it was necessary to dismiss this possibility. This was possible through experiments using birds that are refractory to T. cruzi infection but are permissive to infection only in the first 10 days of embryonic life. When the fertile eggs were inoculated with T. cruzi the breed was born without infection but presenting the kDNA mutation. In this regard, rabbits and birds with kDNA mutation presented typical Chagas disease lesions: minimal rejection unit which is characteristic of the pathology of this disease where the non-parasitized target cell was destroyed by the cells from the vertebrate host´s immune system. These experiments showed that the minimal rejection unit is the common denominator of the pathogenesis of Chagas disease in vertebrate animals. In the chicken model refractory to T. cruzi the cardiomegaly was linked to the minimal rejection unit’s inflammatory infiltration. Therefore the parasite-free chicken heart pathology seen in kDNA-mutated chickens could be linked to the genotype and phenotype alterations. The mechanism whereby these alterations induce the immune rejection of the chicken’s heart requires further investigation.
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