Abstract
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.
Highlights
Trypanosoma cruzi infections (American trypanosomiasis) affect several million people in Latin America [1], usually in the absence of signs and symptoms of an acute illness [2]
The remaining Chagas patient infections were identified by enzyme-linked immunosorbent assay (ELISA), hemagglutination and immunofluorescence assays, which showed specific anti-T. cruzi antibodies in serum samples, and/or by the parasite nDNA signature [7]
The remaining 84 individuals belonged to five families (a, b, c, d, and e). In these patients cryptic T. cruzi infections were detected in the family heads and in some descendants by ELISA, indirect hemagglutination, and immunofluorescence examination, consistently showing specific anti-T. cruzi antibodies [7]
Summary
Trypanosoma cruzi infections (American trypanosomiasis) affect several million people in Latin America [1], usually in the absence of signs and symptoms of an acute illness [2]. The population carrying T. cruzi infections are recognized during epidemiological surveys or routine medical examinations [3]. Less than one third of all the T. cruzi-infected individuals will present symptoms of Chagas disease, usually when they are over 30 years of age. The disease manifests in the heart in 94.5% of cases. The remaining 5.5% affects the esophagus (megaesophagus) or the colon (megacolon). The variable clinical manifestations of Chagas disease are related to disabilities that may accompany a Chagas patient for his entire life [4]
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