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Colciencias
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID)
Wellcome Trust
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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.
Corp Invest Biol, Cellular & Mol Biol Unit, Medellin, Colombia
Univ Antioquia, Inst Biol, Medellin, Colombia
Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
Univ Rosario, Doctoral Program Biomed Sci, Bogota, Colombia
Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA
Univ Estadual Paulista, Inst Biociencias, Botucatu, SP, Brazil
ICBII, Inst Ciencias Biol, Mol Biol Lab, Goiania, Go, Brazil
Univ Brasilia, Inst Ciencias Biol, Brasilia, DF, Brazil
Translat Genom Res Inst North, Div Pathogen Genom, Flagstaff, AZ USA
Univ Rosario, Sch Med & Hlth Sci, Bogota, Colombia
Univ Antioquia, Sch Med, Medellin, Colombia
Univ Estadual Paulista, Inst Biociencias, Botucatu, SP, Brazil
Colciencias: 122256934875
Colciencias: 221365842971
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID): HHSN272200900018C
CNPq: 460999/2014-1
