TY - JOUR
T1 - Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi
AU - Talavera-López, Carlos
AU - Messenger, Louisa A.
AU - Lewis, Michael D.
AU - Yeo, Matthew
AU - Reis-Cunha, João Luís
AU - Matos, Gabriel Machado
AU - Bartholomeu, Daniella C.
AU - Calzada, José E.
AU - Saldaña, Azael
AU - Ramírez, Juan David
AU - Guhl, Felipe
AU - Ocaña-Mayorga, Sofía
AU - Costales, Jaime A.
AU - Gorchakov, Rodion
AU - Jones, Kathryn
AU - Nolan, Melissa S.
AU - Teixeira, Santuza M.R.
AU - Carrasco, Hernán José
AU - Bottazzi, Maria Elena
AU - Hotez, Peter J.
AU - Murray, Kristy O.
AU - Grijalva, Mario J.
AU - Burleigh, Barbara
AU - Grisard, Edmundo C.
AU - Miles, Michael A.
AU - Andersson, Björn
N1 - Publisher Copyright:
© Copyright © 2021 Talavera-López, Messenger, Lewis, Yeo, Reis-Cunha, Matos, Bartholomeu, Calzada, Saldaña, Ramírez, Guhl, Ocaña-Mayorga, Costales, Gorchakov, Jones, Nolan, Teixeira, Carrasco, Bottazzi, Hotez, Murray, Grijalva, Burleigh, Grisard, Miles and Andersson.
PY - 2021/3/3
Y1 - 2021/3/3
N2 - 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.
AB - 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.
KW - Trypanosoma cruzi
KW - antigenic variation
KW - genome sequence
KW - microbial genomics
KW - parasitology
KW - pathology of infectious diseases
KW - population genetics
KW - tropical medicine
UR - http://www.scopus.com/inward/record.url?scp=85102854258&partnerID=8YFLogxK
U2 - 10.3389/fcimb.2021.614665
DO - 10.3389/fcimb.2021.614665
M3 - Article
C2 - 33747978
AN - SCOPUS:85102854258
SN - 2235-2988
VL - 11
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 614665
ER -