ena-STUDY-KAROLINSKA INSITUTET-16-06-2016-10:45:10:649-39
Population genomics of Trypanosoma cruzi DTU-I clade from different locations of America
Trypanosoma cruzi, a Kinetoplastidae protozoan with a dual life cycle and a complex genome, is the causative agent of Chagas’ disease, a severe and debilitating neglected tropical disease affecting almost 10 million people living in poverty in the Americas. The parasite uses a highly variable repertoire of surface molecules to infect cells, evade the immune system and cause disease. The several thousand repetitive surface molecule genes and their variation have been impossible to study due to the lack of a complete reference genome. We here present the most complete genome assembly to date for a T. cruzi DTU-I strain using single molecule sequencing, together with the re-sequencing of 35 T. cruzi DTU-I isolates from different geographic locations, sample sources and clinical outcomes. This high resolution study reveals an unusual Janus-like duality in the organisation of the parasite genome, comprised of a core genomic component that bears resemblance to other protists, but also unique and highly plastic subtelomeric regions encoding surface antigens with interspersed retrotransposons that suggests mechanisms for the generation of new gene variants. The comparative analysis shows active recombination and genetic exchange in T. cruzi. This is the first genome-wide study to include multiple samples from the American continent, providing new insights into population structure and mechanisms of genomic variation.
Trypanosoma cruzi, a Kinetoplastidae protozoan with a dual life cycle and a complex genome, is the causative agent of Chagas’ disease, a severe and debilitating neglected tropical disease affecting almost 10 million people living in poverty in the Americas. The parasite uses a highly variable repertoire of surface molecules to infect cells, evade the immune system and cause disease. The several thousand repetitive surface molecule genes and their variation have been impossible to study due to the lack of a complete reference genome. We here present the most complete genome assembly to date for a T. cruzi DTU-I strain using single molecule sequencing, together with the re-sequencing of 35 T. cruzi DTU-I isolates from different geographic locations, sample sources and clinical outcomes. This high resolution study reveals an unusual Janus-like duality in the organisation of the parasite genome, comprised of a core genomic component that bears resemblance to other protists, but also unique and highly plastic subtelomeric regions encoding surface antigens with interspersed retrotransposons that suggests mechanisms for the generation of new gene variants. The comparative analysis shows active recombination and genetic exchange in T. cruzi. This is the first genome-wide study to include multiple samples from the American continent, providing new insights into population structure and mechanisms of genomic variation.