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Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/61810
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dc.creatorJoão Luísreis-cunhapt_BR
dc.creatorVanessa Gomes Fragapt_BR
dc.creatorLucia Maria da Cunha Galvãopt_BR
dc.creatorLilian Lacerda Buenopt_BR
dc.creatorRicardo Toshio Fujiwarapt_BR
dc.creatorMariana Santos Cardosopt_BR
dc.creatorGustavo Coutinho Cerqueirapt_BR
dc.creatorDaniella c. Bartholomeupt_BR
dc.creatorAnderson Coqueiro-dos-santospt_BR
dc.creatorSamuel Alexandre Pimenta-Carvalhopt_BR
dc.creatorLarissa Pinheiro Marquespt_BR
dc.creatorGabriela F. Rodrigues-luizpt_BR
dc.creatorRodrigo P. Baptistapt_BR
dc.creatorLaila Viana de Almeidapt_BR
dc.creatorNathan Ravi Medeiros Honoratopt_BR
dc.creatorFrancisco Pereira Lobopt_BR
dc.date.accessioned2023-12-06T19:30:58Z-
dc.date.available2023-12-06T19:30:58Z-
dc.date.issued2022-10-20-
dc.citation.volumeXXpt_BR
dc.citation.spagee02319-22pt_BR
dc.citation.epage15pt_BR
dc.identifier.doihttps://doi.org/10.1128/mbio.02319-22pt_BR
dc.identifier.issn2150-7511pt_BR
dc.identifier.urihttp://hdl.handle.net/1843/61810-
dc.description.resumoRepetitive elements cause assembly fragmentation in complex eukaryotic genomes, limiting the study of their variability. The genome of Trypanosoma cruzi, the parasite that causes Chagas disease, has a high repetitive content, including multigene families. Although many T. cruzi multigene families encode surface proteins that play pivotal roles in host-parasite interactions, their variability is currently underestimated, as their high repetitive content results in collapsed gene variants. To estimate sequence variability and copy number variation of multigene families, we developed a read-based approach that is independent of gene-specific read mapping and de novo assembly. This methodology was used to estimate the copy number and variability of MASP, TcMUC, and Trans-Sialidase (TS), the three largest T. cruzi multigene families, in 36 strains, including members of all six parasite discrete typing units (DTUs). We found that these three families present a specific pattern of variability and copy number among the distinct parasite DTUs. Inter-DTU hybrid strains presented a higher variability of these families, suggesting that maintaining a larger content of their members could be advantageous. In addition, in a chronic murine model and chronic Chagasic human patients, the immune response was focused on TS antigens, suggesting that targeting TS conserved sequences could be a potential avenue to improve diagnosis and vaccine design against Chagas disease. Finally, the proposed approach can be applied to study multicopy genes in any organism, opening new avenues to access sequence variability in complex genomes. IMPORTANCE Sequences that have several copies in a genome, such as multicopy-gene families, mobile elements, and microsatellites, are among the most challenging genomic segments to study. They are frequently underestimated in genome assemblies, hampering the correct assessment of these important players in genome evolution and adaptation. Here, we developed a new methodology to estimate variability and copy numbers of repetitive genomic regions and employed it to characterize the T. cruzi multigene families MASP, TcMUC, and transsialidase (TS), which are important virulence factors in this parasite. We showed that multigene families vary in sequence and content among the parasite’s lineages, whereas hybrid strains have a higher sequence variability that could be advantageous to the parasite's survivability. By identifying conserved sequences within multigene families, we showed that the mammalian host immune response toward these multigene families is usually focused on the TS multigene family. These TS conserved and immunogenic peptides can be explored in future works as diagnostic targets or vaccine candidates for Chagas disease. Finally, this methodology can be easily applied to any organism of interest, which will aid in our understanding of complex genomic regions.pt_BR
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorpt_BR
dc.format.mimetypepdfpt_BR
dc.languageengpt_BR
dc.publisherUniversidade Federal de Minas Geraispt_BR
dc.publisher.countryBrasilpt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIApt_BR
dc.publisher.departmentICB - DEPARTAMENTO DE PARASITOLOGIApt_BR
dc.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICASpt_BR
dc.publisher.initialsUFMGpt_BR
dc.relation.ispartofmBiopt_BR
dc.rightsAcesso Abertopt_BR
dc.subjectMulticopy genespt_BR
dc.subjectVariabilitypt_BR
dc.subjectCopy number variationpt_BR
dc.subjectComplex genomespt_BR
dc.subjectT. cruzipt_BR
dc.subjectMASPpt_BR
dc.subjectMucinspt_BR
dc.subjectTranssialidasespt_BR
dc.subjectAntigenicitypt_BR
dc.subject.otherAntígenospt_BR
dc.subject.otherMuseuspt_BR
dc.subject.otherTrypanosoma cruzipt_BR
dc.subject.otherGenomaspt_BR
dc.subject.otherGenespt_BR
dc.titleAccessing the Variability of Multicopy Genes in Complex Genomes using Unassembled Next-Generation Sequencing Reads: The Case of Trypanosoma cruzi Multigene Familiespt_BR
dc.typeArtigo de Periódicopt_BR
dc.url.externahttps://journals.asm.org/doi/10.1128/mbio.02319-22pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0003-0974-7357pt_BR
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