Inheritance of DNA transferred from American trypanosomes to human hosts.
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.
Hecht
Mariana M
MM
Chagas Disease Multidisciplinary Research Laboratory, Faculty of Medicine, University of Brasilia, Brasília, Federal District, Brazil.
Nitz
Nadjar
N
Araujo
Perla F
PF
Sousa
Alessandro O
AO
Rosa
Ana de Cássia
Ade C
Gomes
Dawidson A
DA
Leonardecz
Eduardo
E
Teixeira
Antonio R L
AR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001938:Brazil; D014355:Chagas Disease / Q000235:genetics* / Q000469:parasitology; D002648:Child; D016054:DNA, Protozoan / Q000235:genetics*; D005260:Female; D022761:Gene Transfer, Horizontal; D015894:Genome, Human / Q000235:genetics; D005843:Geography; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000502:physiology; D020298:U937 Cells; D055815:Young Adult
D016054:DNA, Protozoan