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

José F Muñoz, Rhys A Farrer, Christopher A Desjardins, Juan E Gallo, Sean Sykes, Sharadha Sakthikumar, Elizabeth Misas, Emily A Whiston, Eduardo Bagagli, Celia M A Soares, Marcus de M Teixeira, John W Taylor, Oliver K Clay, Juan G McEwen, Christina A Cuomo (Corresponding Author)

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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 insights 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.

Original languageEnglish
Article numbere00213-16
Number of pages18
Issue number5
Early online date28 Sept 2016
Publication statusPublished - 6 Oct 2016

Bibliographical note

We thank Angela Restrepo, Rosana Puccia, Zoilo Pires de Camargo, and Maria Sueli Felipe for kindly providing the isolates for this study.

This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272200900018C. This work was partly supported by Colciencias via the grants “A Gene Atlas for Human Pathogenic Fungi” (122256934875) and “A Comprehensive Genomic and Transcriptomic Analysis of Dimorphic Human Pathogen Fungi and Its Relation with Virulence” (221365842971) and by the Universidad de Antioquia via a “Sostenibilidad 2015/2016” grant. Colciencias National Doctorate Program funding supported J.F.M.; Enlaza Mundos partly supported his fellowship. The Wellcome Trust supported R.A.F.


  • Paracoccidioides
  • evolution
  • genetic recombination
  • genome analysis
  • mycology
  • population genetics


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