Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides

Detalhes bibliográficos
Autor(a) principal: Munoz, Jose F.
Data de Publicação: 2016
Outros Autores: Farrer, Rhys A., Desjardins, Christopher A., Gallo, Juan E., Sykes, Sean, Sakthikumar, Sharadha, Misas, Elizabeth, Whiston, Emily A., Bagagli, Eduardo [UNESP], Soares, Celia M. A., Teixeira, Marcus de M., Bagagli, Eduardo, Taylor, John W., Clay, Oliver K., McEwen, Juan G., Cuomo, Christina A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1128/mSphere.00213-16
http://hdl.handle.net/11449/165449
Resumo: The Paracoccidioides genus includes two species of thermally dimorphic fungi that cause paracoccidioidomycosis, a neglected health-threatening human systemic mycosis endemic to Latin America. To examine the genome evolution and the diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31 isolates representing the phylogenetic, geographic, and ecological breadth of the genus. These samples included clinical, environmental and laboratory reference strains of the S1, PS2, PS3, and PS4 lineages of P. brasiliensis and also isolates of Paracoccidioides lutzii species. We completed the first annotated genome assemblies for the PS3 and PS4 lineages and found that gene order was highly conserved across the major lineages, with only a few chromosomal rearrangements. Comparing whole-genome assemblies of the major lineages with single-nucleotide polymorphisms (SNPs) predicted from the remaining 26 isolates, we identified a deep split of the S1 lineage into two clades we named S1a and S1b. We found evidence for greater genetic exchange between the S1b lineage and all other lineages; this may reflect the broad geographic range of S1b, which is often sympatric with the remaining, largely geographically isolated lineages. In addition, we found evidence of positive selection for the GP43 and PGA1 antigen genes and genes coding for other secreted proteins and proteases and lineage-specific loss-of-function mutations in cell wall and protease genes; these together may contribute to virulence and host immune response variation among natural isolates of Paracoccidioides spp. These in-sights into the recent evolutionary events highlight important differences between the lineages that could impact the distribution, pathogenicity, and ecology of Paracoccidioides. IMPORTANCE Characterization of genetic differences between lineages of the dimorphic human-pathogenic fungus Paracoccidioides can identify changes linked to important phenotypes and guide the development of new diagnostics and treatments. In this article, we compared genomes of 31 diverse isolates representing the major lineages of Paracoccidioides spp. and completed the first annotated genome sequences for the PS3 and PS4 lineages. We analyzed the population structure and characterized the genetic diversity among the lineages of Paracoccidioides, including a deep split of S1 into two lineages (S1a and S1b), and differentiated S1b, associated with most clinical cases, as the more highly recombining and diverse lineage. In addition, we found patterns of positive selection in surface proteins and secreted enzymes among the lineages, suggesting diversifying mechanisms of pathogenicity and adaptation across this species complex. These genetic differences suggest associations with the geographic range, pathogenicity, and ecological niches of Paracoccidioides lineages.
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spelling Genome Diversity, Recombination, and Virulence across the Major Lineages of ParacoccidioidesParacoccidioidesevolutiongenetic recombinationgenome analysismycologypopulation geneticsThe Paracoccidioides genus includes two species of thermally dimorphic fungi that cause paracoccidioidomycosis, a neglected health-threatening human systemic mycosis endemic to Latin America. To examine the genome evolution and the diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31 isolates representing the phylogenetic, geographic, and ecological breadth of the genus. These samples included clinical, environmental and laboratory reference strains of the S1, PS2, PS3, and PS4 lineages of P. brasiliensis and also isolates of Paracoccidioides lutzii species. We completed the first annotated genome assemblies for the PS3 and PS4 lineages and found that gene order was highly conserved across the major lineages, with only a few chromosomal rearrangements. Comparing whole-genome assemblies of the major lineages with single-nucleotide polymorphisms (SNPs) predicted from the remaining 26 isolates, we identified a deep split of the S1 lineage into two clades we named S1a and S1b. We found evidence for greater genetic exchange between the S1b lineage and all other lineages; this may reflect the broad geographic range of S1b, which is often sympatric with the remaining, largely geographically isolated lineages. In addition, we found evidence of positive selection for the GP43 and PGA1 antigen genes and genes coding for other secreted proteins and proteases and lineage-specific loss-of-function mutations in cell wall and protease genes; these together may contribute to virulence and host immune response variation among natural isolates of Paracoccidioides spp. These in-sights into the recent evolutionary events highlight important differences between the lineages that could impact the distribution, pathogenicity, and ecology of Paracoccidioides. IMPORTANCE Characterization of genetic differences between lineages of the dimorphic human-pathogenic fungus Paracoccidioides can identify changes linked to important phenotypes and guide the development of new diagnostics and treatments. In this article, we compared genomes of 31 diverse isolates representing the major lineages of Paracoccidioides spp. and completed the first annotated genome sequences for the PS3 and PS4 lineages. We analyzed the population structure and characterized the genetic diversity among the lineages of Paracoccidioides, including a deep split of S1 into two lineages (S1a and S1b), and differentiated S1b, associated with most clinical cases, as the more highly recombining and diverse lineage. In addition, we found patterns of positive selection in surface proteins and secreted enzymes among the lineages, suggesting diversifying mechanisms of pathogenicity and adaptation across this species complex. These genetic differences suggest associations with the geographic range, pathogenicity, and ecological niches of Paracoccidioides lineages.ColcienciasHHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)Wellcome TrustConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Corp Invest Biol, Cellular & Mol Biol Unit, Medellin, ColombiaUniv Antioquia, Inst Biol, Medellin, ColombiaBroad Inst MIT & Harvard, Cambridge, MA 02142 USAUniv Rosario, Doctoral Program Biomed Sci, Bogota, ColombiaUniv Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USAUniv Estadual Paulista, Inst Biociencias, Botucatu, SP, BrazilICBII, Inst Ciencias Biol, Mol Biol Lab, Goiania, Go, BrazilUniv Brasilia, Inst Ciencias Biol, Brasilia, DF, BrazilTranslat Genom Res Inst North, Div Pathogen Genom, Flagstaff, AZ USAUniv Rosario, Sch Med & Hlth Sci, Bogota, ColombiaUniv Antioquia, Sch Med, Medellin, ColombiaUniv Estadual Paulista, Inst Biociencias, Botucatu, SP, BrazilColciencias: 122256934875Colciencias: 221365842971HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): HHSN272200900018CCNPq: 460999/2014-1Amer Soc MicrobiologyCorp Invest BiolUniv AntioquiaBroad Inst MIT & HarvardUniv RosarioUniv Calif BerkeleyUniversidade Estadual Paulista (Unesp)ICBIIUniversidade de Brasília (UnB)Translat Genom Res Inst NorthMunoz, Jose F.Farrer, Rhys A.Desjardins, Christopher A.Gallo, Juan E.Sykes, SeanSakthikumar, SharadhaMisas, ElizabethWhiston, Emily A.Bagagli, Eduardo [UNESP]Soares, Celia M. A.Teixeira, Marcus de M.Bagagli, EduardoTaylor, John W.Clay, Oliver K.McEwen, Juan G.Cuomo, Christina A.2018-11-28T03:37:22Z2018-11-28T03:37:22Z2016-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article18application/pdfhttp://dx.doi.org/10.1128/mSphere.00213-16Msphere. Washington: Amer Soc Microbiology, v. 1, n. 5, 18 p., 2016.2379-5042http://hdl.handle.net/11449/16544910.1128/mSphere.00213-16WOS:000392586800009WOS000392586800009.pdf33203275704295390000-0002-8003-4109Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMsphere2,030info:eu-repo/semantics/openAccess2023-12-31T06:17:14Zoai:repositorio.unesp.br:11449/165449Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T21:45:56.878342Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
title Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
spellingShingle Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
Munoz, Jose F.
Paracoccidioides
evolution
genetic recombination
genome analysis
mycology
population genetics
title_short Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
title_full Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
title_fullStr Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
title_full_unstemmed Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
title_sort Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides
author Munoz, Jose F.
author_facet Munoz, Jose F.
Farrer, Rhys A.
Desjardins, Christopher A.
Gallo, Juan E.
Sykes, Sean
Sakthikumar, Sharadha
Misas, Elizabeth
Whiston, Emily A.
Bagagli, Eduardo [UNESP]
Soares, Celia M. A.
Teixeira, Marcus de M.
Bagagli, Eduardo
Taylor, John W.
Clay, Oliver K.
McEwen, Juan G.
Cuomo, Christina A.
author_role author
author2 Farrer, Rhys A.
Desjardins, Christopher A.
Gallo, Juan E.
Sykes, Sean
Sakthikumar, Sharadha
Misas, Elizabeth
Whiston, Emily A.
Bagagli, Eduardo [UNESP]
Soares, Celia M. A.
Teixeira, Marcus de M.
Bagagli, Eduardo
Taylor, John W.
Clay, Oliver K.
McEwen, Juan G.
Cuomo, Christina A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Corp Invest Biol
Univ Antioquia
Broad Inst MIT & Harvard
Univ Rosario
Univ Calif Berkeley
Universidade Estadual Paulista (Unesp)
ICBII
Universidade de Brasília (UnB)
Translat Genom Res Inst North
dc.contributor.author.fl_str_mv Munoz, Jose F.
Farrer, Rhys A.
Desjardins, Christopher A.
Gallo, Juan E.
Sykes, Sean
Sakthikumar, Sharadha
Misas, Elizabeth
Whiston, Emily A.
Bagagli, Eduardo [UNESP]
Soares, Celia M. A.
Teixeira, Marcus de M.
Bagagli, Eduardo
Taylor, John W.
Clay, Oliver K.
McEwen, Juan G.
Cuomo, Christina A.
dc.subject.por.fl_str_mv Paracoccidioides
evolution
genetic recombination
genome analysis
mycology
population genetics
topic Paracoccidioides
evolution
genetic recombination
genome analysis
mycology
population genetics
description The Paracoccidioides genus includes two species of thermally dimorphic fungi that cause paracoccidioidomycosis, a neglected health-threatening human systemic mycosis endemic to Latin America. To examine the genome evolution and the diversity of Paracoccidioides spp., we conducted whole-genome sequencing of 31 isolates representing the phylogenetic, geographic, and ecological breadth of the genus. These samples included clinical, environmental and laboratory reference strains of the S1, PS2, PS3, and PS4 lineages of P. brasiliensis and also isolates of Paracoccidioides lutzii species. We completed the first annotated genome assemblies for the PS3 and PS4 lineages and found that gene order was highly conserved across the major lineages, with only a few chromosomal rearrangements. Comparing whole-genome assemblies of the major lineages with single-nucleotide polymorphisms (SNPs) predicted from the remaining 26 isolates, we identified a deep split of the S1 lineage into two clades we named S1a and S1b. We found evidence for greater genetic exchange between the S1b lineage and all other lineages; this may reflect the broad geographic range of S1b, which is often sympatric with the remaining, largely geographically isolated lineages. In addition, we found evidence of positive selection for the GP43 and PGA1 antigen genes and genes coding for other secreted proteins and proteases and lineage-specific loss-of-function mutations in cell wall and protease genes; these together may contribute to virulence and host immune response variation among natural isolates of Paracoccidioides spp. These in-sights into the recent evolutionary events highlight important differences between the lineages that could impact the distribution, pathogenicity, and ecology of Paracoccidioides. IMPORTANCE Characterization of genetic differences between lineages of the dimorphic human-pathogenic fungus Paracoccidioides can identify changes linked to important phenotypes and guide the development of new diagnostics and treatments. In this article, we compared genomes of 31 diverse isolates representing the major lineages of Paracoccidioides spp. and completed the first annotated genome sequences for the PS3 and PS4 lineages. We analyzed the population structure and characterized the genetic diversity among the lineages of Paracoccidioides, including a deep split of S1 into two lineages (S1a and S1b), and differentiated S1b, associated with most clinical cases, as the more highly recombining and diverse lineage. In addition, we found patterns of positive selection in surface proteins and secreted enzymes among the lineages, suggesting diversifying mechanisms of pathogenicity and adaptation across this species complex. These genetic differences suggest associations with the geographic range, pathogenicity, and ecological niches of Paracoccidioides lineages.
publishDate 2016
dc.date.none.fl_str_mv 2016-09-01
2018-11-28T03:37:22Z
2018-11-28T03:37:22Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1128/mSphere.00213-16
Msphere. Washington: Amer Soc Microbiology, v. 1, n. 5, 18 p., 2016.
2379-5042
http://hdl.handle.net/11449/165449
10.1128/mSphere.00213-16
WOS:000392586800009
WOS000392586800009.pdf
3320327570429539
0000-0002-8003-4109
url http://dx.doi.org/10.1128/mSphere.00213-16
http://hdl.handle.net/11449/165449
identifier_str_mv Msphere. Washington: Amer Soc Microbiology, v. 1, n. 5, 18 p., 2016.
2379-5042
10.1128/mSphere.00213-16
WOS:000392586800009
WOS000392586800009.pdf
3320327570429539
0000-0002-8003-4109
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Msphere
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dc.publisher.none.fl_str_mv Amer Soc Microbiology
publisher.none.fl_str_mv Amer Soc Microbiology
dc.source.none.fl_str_mv Web of Science
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