| Title: | Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex |
| Author(s): | Feretzaki M; Billmyre RB; Clancey SA; Wang X; Heitman J; |
| Address: | "Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America" |
| DOI: | 10.1371/journal.pgen.1005868 |
| ISSN/ISBN: | 1553-7404 (Electronic) 1553-7390 (Print) 1553-7390 (Linking) |
| Abstract: | "RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes, including maintenance of genome stability and repression of transposon expression and movement. However, a number of organisms have lost their RNAi pathways, including the model yeast Saccharomyces cerevisiae, the maize pathogen Ustilago maydis, the human pathogen Cryptococcus deuterogattii, and some human parasite pathogens, suggesting there may be adaptive benefits associated with both retention and loss of RNAi. By comparing the RNAi-deficient genome of the Pacific Northwest Outbreak C. deuterogattii strain R265 with the RNAi-proficient genomes of the Cryptococcus pathogenic species complex, we identified a set of conserved genes that were lost in R265 and all other C. deuterogattii isolates examined. Genetic and molecular analyses reveal several of these lost genes play roles in RNAi pathways. Four novel components were examined further. Znf3 (a zinc finger protein) and Qip1 (a homolog of N. crassa Qip) were found to be essential for RNAi, while Cpr2 (a constitutive pheromone receptor) and Fzc28 (a transcription factor) are involved in sex-induced but not mitosis-induced silencing. Our results demonstrate that the mitotic and sex-induced RNAi pathways rely on the same core components, but sex-induced silencing may be a more specific, highly induced variant that involves additional specialized or regulatory components. Our studies further illustrate how gene network polymorphisms involving known components of key cellular pathways can inform identification of novel elements and suggest that RNAi loss may have been a core event in the speciation of C. deuterogattii and possibly contributed to its pathogenic trajectory" |
| Keywords: | "Cryptococcus/*genetics/pathogenicity Fungal Proteins/genetics *Gene Regulatory Networks Genome, Fungal Humans Polymorphism, Genetic *RNA Interference Signal Transduction;" |
| Notes: | "MedlineFeretzaki, Marianna Billmyre, R Blake Clancey, Shelly Applen Wang, Xuying Heitman, Joseph eng R01 AI039115/AI/NIAID NIH HHS/ R37 AI039115/AI/NIAID NIH HHS/ T32 GM007184/GM/NIGMS NIH HHS/ AI39115-18/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural 2016/03/05 PLoS Genet. 2016 Mar 4; 12(3):e1005868. doi: 10.1371/journal.pgen.1005868. eCollection 2016 Mar" |
