Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi
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, immu...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2021-03-01
|
Series: | Frontiers in Cellular and Infection Microbiology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.614665/full |
id |
doaj-a4cd59512a324280b349602a5bf83648 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carlos Talavera-López Carlos Talavera-López Louisa A. Messenger Michael D. Lewis Matthew Yeo João Luís Reis-Cunha Gabriel Machado Matos Daniella C. Bartholomeu José E. Calzada Azael Saldaña Juan David Ramírez Felipe Guhl Sofía Ocaña-Mayorga Jaime A. Costales Rodion Gorchakov Kathryn Jones Melissa S. Nolan Santuza M. R. Teixeira Hernán José Carrasco Maria Elena Bottazzi Peter J. Hotez Kristy O. Murray Mario J. Grijalva Mario J. Grijalva Barbara Burleigh Edmundo C. Grisard Michael A. Miles Björn Andersson |
spellingShingle |
Carlos Talavera-López Carlos Talavera-López Louisa A. Messenger Michael D. Lewis Matthew Yeo João Luís Reis-Cunha Gabriel Machado Matos Daniella C. Bartholomeu José E. Calzada Azael Saldaña Juan David Ramírez Felipe Guhl Sofía Ocaña-Mayorga Jaime A. Costales Rodion Gorchakov Kathryn Jones Melissa S. Nolan Santuza M. R. Teixeira Hernán José Carrasco Maria Elena Bottazzi Peter J. Hotez Kristy O. Murray Mario J. Grijalva Mario J. Grijalva Barbara Burleigh Edmundo C. Grisard Michael A. Miles Björn Andersson Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi Frontiers in Cellular and Infection Microbiology Trypanosoma cruzi genome sequence antigenic variation population genetics parasitology microbial genomics |
author_facet |
Carlos Talavera-López Carlos Talavera-López Louisa A. Messenger Michael D. Lewis Matthew Yeo João Luís Reis-Cunha Gabriel Machado Matos Daniella C. Bartholomeu José E. Calzada Azael Saldaña Juan David Ramírez Felipe Guhl Sofía Ocaña-Mayorga Jaime A. Costales Rodion Gorchakov Kathryn Jones Melissa S. Nolan Santuza M. R. Teixeira Hernán José Carrasco Maria Elena Bottazzi Peter J. Hotez Kristy O. Murray Mario J. Grijalva Mario J. Grijalva Barbara Burleigh Edmundo C. Grisard Michael A. Miles Björn Andersson |
author_sort |
Carlos Talavera-López |
title |
Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi |
title_short |
Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi |
title_full |
Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi |
title_fullStr |
Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi |
title_full_unstemmed |
Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruzi |
title_sort |
repeat-driven generation of antigenic diversity in a major human pathogen, trypanosoma cruzi |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2021-03-01 |
description |
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. |
topic |
Trypanosoma cruzi genome sequence antigenic variation population genetics parasitology microbial genomics |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2021.614665/full |
work_keys_str_mv |
AT carlostalaveralopez repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT carlostalaveralopez repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT louisaamessenger repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT michaeldlewis repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT matthewyeo repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT joaoluisreiscunha repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT gabrielmachadomatos repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT daniellacbartholomeu repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT joseecalzada repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT azaelsaldana repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT juandavidramirez repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT felipeguhl repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT sofiaocanamayorga repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT jaimeacostales repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT rodiongorchakov repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT kathrynjones repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT melissasnolan repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT santuzamrteixeira repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT hernanjosecarrasco repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT mariaelenabottazzi repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT peterjhotez repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT kristyomurray repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT mariojgrijalva repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT mariojgrijalva repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT barbaraburleigh repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT edmundocgrisard repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT michaelamiles repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi AT bjornandersson repeatdrivengenerationofantigenicdiversityinamajorhumanpathogentrypanosomacruzi |
_version_ |
1724233359801974784 |
spelling |
doaj-a4cd59512a324280b349602a5bf836482021-03-03T05:09:02ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-03-011110.3389/fcimb.2021.614665614665Repeat-Driven Generation of Antigenic Diversity in a Major Human Pathogen, Trypanosoma cruziCarlos Talavera-López0Carlos Talavera-López1Louisa A. Messenger2Michael D. Lewis3Matthew Yeo4João Luís Reis-Cunha5Gabriel Machado Matos6Daniella C. Bartholomeu7José E. Calzada8Azael Saldaña9Juan David Ramírez10Felipe Guhl11Sofía Ocaña-Mayorga12Jaime A. Costales13Rodion Gorchakov14Kathryn Jones15Melissa S. Nolan16Santuza M. R. Teixeira17Hernán José Carrasco18Maria Elena Bottazzi19Peter J. Hotez20Kristy O. Murray21Mario J. Grijalva22Mario J. Grijalva23Barbara Burleigh24Edmundo C. Grisard25Michael A. Miles26Björn Andersson27Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, SwedenEuropean Bioinformatics Institute, Wellcome Sanger Institute, Hinxton, United KingdomFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Biologia Celular, Embriologia e Genética, Universidade Federal Santa Catarina, Florianópolis, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Parasitología, Instituto Conmemorativo Gorgas de Estudios de la Salud, Ciudad de Panamá, PanamaDepartamento de Parasitología, Instituto Conmemorativo Gorgas de Estudios de la Salud, Ciudad de Panamá, PanamaGrupo de Investigaciones Microbiológicas-UR (GIMUR), Departamento de Biología, Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, ColombiaGrupo de Investigaciones en Microbiología y Parasitología Tropical (CIMPAT), Tropical Parasitology Research Center, Universidad de Los Andes, Bogotá, ColombiaCentro de Investigación para la Salud en América Latina (CISeAL), Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, EcuadorCentro de Investigación para la Salud en América Latina (CISeAL), Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United States0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United States0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United States1Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil2Laboratorio de Biología Molecular de Protozoarios, Instituto de Medicina Tropical, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United States0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United States0Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, National School of Tropical Medicine, Department of Pediatrics - Tropical Medicine, Baylor College of Medicine, Houston, TX, United StatesCentro de Investigación para la Salud en América Latina (CISeAL), Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador3Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Infectious and Tropical Disease Institute, Ohio University, Athens, OH, United States4Department of Immunology and Infectious Diseases, T.H. Chan School of Public Health, Harvard University, Boston, MA, United States5Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal Santa Catarina, Florianópolis, BrazilFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United KingdomDepartment of Cell and Molecular Biology, Karolinska Institutet, Stockholm, SwedenTrypanosoma 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.https://www.frontiersin.org/articles/10.3389/fcimb.2021.614665/fullTrypanosoma cruzigenome sequenceantigenic variationpopulation geneticsparasitologymicrobial genomics |