Abstract
Trypanosoma cruzi, a zoonotic kinetoplastid protozoan parasite, is the causative agent of American trypanosomiasis (Chagas disease). Having a very plastic, repetitive and complex genome, the parasite displays a highly diverse repertoire of surface molecules, with pivotal roles in cell invasion, immune evasion and pathogenesis. Before 2016, the complexity of the genomic regions containing these genes impaired the assembly of a genome at chromosomal level, making it impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here describe the genome assembly of the Sylvio X10/1 genome sequence, which since 2016 has been used as a reference genome sequence for T. cruzi clade I (TcI), produced using high coverage PacBio single-molecule sequencing. It was used to analyze deep Illumina sequence data from 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene distribution showed the unusual duality in the organization of the parasite genome, a synteny of the core genomic region with related protozoa flanked by unique and highly plastic multigene family clusters encoding surface antigens. The presence of abundant interspersed retrotransposons in these multigene family clusters suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response on these TcI strains. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure.
Highlights
Trypanosoma cruzi is a kinetoplastid protozoan and the etiologic agent of Chagas disease, considered one of the most important human parasitic disease in Latin America
Comparison with the available short read assembly of the TcVI strain CL Brener revealed conserved core syntenic blocks composed of stretches of homologous sequences separated by non-syntenic regions (Figure 1B and Supplementary Table 2) that corresponded to regions that were in some cases initially not reconstructed in the hybrid TcVI strain, but have been partially resolved in later versions of this genome sequence
The length of the Pacific Biosciences (PacBio) reads and the high coverage allowed the reconstruction of long stretches of repetitive sequences in the Sylvio X10/1 genome that could previously not be resolved using shorter read data for this genome
Summary
Trypanosoma cruzi is a kinetoplastid protozoan and the etiologic agent of Chagas disease, considered one of the most important human parasitic disease in Latin America. In 2015, 5,742,167 people were estimated to be infected with T. cruzi in 21 Latin American countries and around 13% of the Latin American population is at risk of contracting T. cruzi infection due to domicile infestation of triatomine bugs or due to non-vectorial transmission via blood transfusion, organ transplant, oral, congenital or accidental infection The migration of infected humans to non-endemic areas has made it a new public health threat in other geographic areas such as North America, Europe and Asia (Bern, 2015). Sylvatic T. cruzi transmission cycles, often associated with human disease, have been described in areas formerly considered as free from this disease such as in Texas (USA) (Bern, 2015)
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