September 22, 2019  |  

Repeat-driven generation of antigenic diversity in a major human pathogen, Trypanosoma cruzi

Authors: Talavera-Lopez, Carlos and Messenger, Louisa A and Lewis, Michael D and Yeo, Matthew and Reis-Cunha, Joao Luis and Bartholomeu, Daniella C and Calzada, Jose E and Saldana, Azael and Ramirez, Juan David and Guhl, Felipe and Ocana-Mayorga, Sofia and Costales, Jaime A and Gorchakov, Rodion and Jones, Kathryn and Nolan Garcia, Melissa and Carrasco, Hernan and Grisard, Edmundo Carlos and Teixeira, Santuza M R and Bottazzi, Maria Elena and Hotez, Peter J and Murray, Kristy O and Grijalva, Mario J and Burleigh, Barbara and Miles, Michael A and Andersson, Bjorn

Trypanosoma cruzi, a zoonotic kinetoplastid protozoan with a complex genome, is the causative agent of American trypanosomiasis (Chagas disease). The parasite uses a highly diverse repertoire of surface molecules, with roles in cell invasion, immune evasion and pathogenesis. Thus far, the genomic regions containing these genes have been impossible to resolve and it has been impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here present an improved genome assembly of a T. cruzi clade I (TcI) strain using high coverage PacBio single molecule sequencing, together with Illumina sequencing of 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene structure reveals an unusual duality in the organisation of the parasite genome, a core genomic region syntenous with related protozoa flanked by unique and highly plastic subtelomeric regions encoding surface antigens. The presence of abundant interspersed retrotransposons in the subtelomeres suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response. 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.

Journal: BioRxiv
DOI: 10.1101/283531
Year: 2018

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