Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex
- Duke University Medical Center, United States
- Broad Institute, United States
- Westerdijk Fungal Biodiversity Institute, Netherlands
- CNRS, University Evry, France
- Ruhr-University Bochum, Germany
Abstract
Sexual reproduction is a ubiquitous and ancient trait of eukaryotic life. While sexual organisms are usually faced with the challenge of finding a compatible mating partner, species as diverse as animals, plants, and fungi have repeatedly evolved the ability to reproduce sexually without an obligate requirement for another individual. Here, we uncovered the underlying mechanism of self-compatibility (homothallism) in Cryptococcus depauperatus, a fungal species sister to the clinically relevant human fungal pathogens Cryptococcus neoformans and Cryptococcus gattii species complexes. In contrast to C. neoformans or C. gattii, which grow as a yeast in the asexual stage, and produce hyphae, basidia, and infectious spores during the sexual stage, C. depauperatus grows exclusively as hyphae decorated with basidia and abundant spores and appears to be continuously engaged in sexual reproduction. By combining the insights from comparative genomics and genetic analyses of mutants defective in key mating and meiosis genes, we demonstrate the sexual cycle of C. depauperatus involves meiosis, and reveal that self-compatibility is orchestrated by the expression, in the same cell, of an unlinked mating receptor (Ste3a) and pheromone ligand (MFa) pair seemingly derived from opposite mating types of a heterothallic (self-sterile) ancestor. We identified a putative mating-type (MAT) determining region containing genes phylogenetically aligned with MAT<strong>a</strong> alleles of other species, and a few MATa gene alleles scattered and unlinked throughout the genome, but no homologs of the mating-type homeodomain genes SXI1 (HD1) and SXI2 (HD2). Comparative genomic analyses suggested a dramatic remodeling of the MAT locus possibly owing to reduced selective constraints to maintain mating-type genes in tight linkage, associated with a transition to self-fertility. Our findings support C. depauperatus as an obligately sexual, homothallic fungal species and provide additional insight into the repeated transitions between modes of sexual reproduction that have occurred throughout the fungal kingdom.
Data availability
Sequencing reads and genome assemblies of C. depauperatus CBS7841 and CBS7855 were submitted to GenBank under BioProjects PRJNA200572 and PRJNA200573, respectively. All other genomic data (RNA-seq and Illumina sequence of C. depauperatus CBS7841 can1 mutants) are available under BioProject PRJNA803141. Source data files have been provided for Figures 1 to 7.
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Cryptotoccus SequencingNCBI BioProject, PRJNA200572.
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Cryptotoccus SequencingNCBI BioProject, PRJNA200573.
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Cryptococcus depauperatus raw sequence readsNCBI BioProject, PRJNA803141.
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Cryptococcus neoformans var. grubii H99 genomeNCBI BioProject, PRJNA411.
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Cryptotoccus SequencingNCBI BioProject, PRJNA200571.
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Cryptotoccus SequencingNCBI BioProject, PRJNA191370.
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Cryptococcus floricola strain DSM 27421 Genome sequencing and assemblyNCBI BioProject, PRJNA496466.
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Cryptococcus wingfieldii strain CBS7118 Genome sequencing and assemblyNCBI BioProject, PRJNA496468.
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WGS sequencing of strain JEC21 (serotype D)NCBI BioProject, PRJNA13856.
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Cryptococcus gattii WM276 RefSeq GenomeNCBI BioProject, PRJNA62089.
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Kwoniella mangroviensis CBS 8507NCBI BioProject, PRJNA352839.
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Kwoniella mangroviensis CBS 10435NCBI BioProject, PRJNA202099.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI50113-17)
- Joseph Heitman
National Institute of Allergy and Infectious Diseases (AI39115-24)
- Joseph Heitman
National Institute of Allergy and Infectious Diseases (AI33654-04)
- Joseph Heitman
National Institutes of Health (U54HG003067)
- Christina A Cuomo
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antonis Rokas, Vanderbilt University, United States
Version history
- Preprint posted: March 30, 2022 (view preprint)
- Received: March 31, 2022
- Accepted: June 15, 2022
- Accepted Manuscript published: June 17, 2022 (version 1)
- Version of Record published: July 19, 2022 (version 2)
Copyright
© 2022, Passer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex
eLife 11:e79114.
https://doi.org/10.7554/eLife.79114
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