Variação de número de cópias revela extensa plasticidade genômica no parasito Trypanosoma cruzi

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease, a chronic illness that affects ~5-8 million people worldwide. This parasite has extreme genotypic and phenotypic variability, with several aneuploidies and a massive expansion of repetitive multigene families enrolled in host-parasite interactions. Although aneuploidies are usually associated with debilitating phenotypes in superior eukaryotes, recent data showed that it could also provide increased fitness in stress conditions and generate drug resistance in unicellular eukaryotes. Even though studies point toward karyotype variability in T. cruzi, the extent of chromosomal copy number variation (CCNV) in this parasite has not been determined yet. To identify CCNV in T. cruzi, we sequenced the genomes of lab-derived and field-isolated strains from subgroups usually associated to human infections, and estimated the ploidy of each chromosome based on read depth coverage. We have shown that the pattern of CCNV varies among and within T. cruzi subgroups, but seems stable inside a given population. Chromosome 31, the only supernumerary chromosome in all T. cruzi samples, is enriched with genes related to glycosylation pathways, such as the enzyme UDP-GlcNAc-dependent glycosyltransferase involved in the initial steps of mucins glycosylation, which is a protein that covers the entire parasites surface and is enrolled in the adhesion and cellular invasion of mammalian cells. Besides aneuploidies, T. cruzi also relies on the expansion of multigene families to generate variability and to adapt to new environments. Although these families are highly polymorphic, they also present motifs shared among distinct members, resulting in a mosaic structure that favors the generation of sequence variability by rearrangement of defined blocks, through recombination. We have estimated the relative abundance of these conserved motifs among T. cruzi strains, providing insights into the evolution of these gene families and opening new avenues for identifying new potential vaccine and diagnosis targets for Chagas disease.