Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex

  1. Andrew Ryan Passer
  2. Shelly Applen Clancey
  3. Terrance Shea
  4. Márcia David-Palma
  5. Anna Floyd Averette
  6. Teun Boekhout
  7. Betina M Porcel
  8. Minou Nowrousian
  9. Christina A Cuomo
  10. Sheng Sun
  11. Joseph Heitman  Is a corresponding author
  12. Marco A Coelho  Is a corresponding author
  1. Duke University Medical Center, United States
  2. Broad Institute, United States
  3. Westerdijk Fungal Biodiversity Institute, Netherlands
  4. CNRS, University Evry, France
  5. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Andrew Ryan Passer

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Shelly Applen Clancey

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Terrance Shea

    Broad Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Márcia David-Palma

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Anna Floyd Averette

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Teun Boekhout

    Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Betina M Porcel

    Génomique Métabolique, CNRS, University Evry, Evry, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Minou Nowrousian

    Lehrstuhl fuer Allgemeine und Molekulare Botanik, Ruhr-University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0075-6695
  9. Christina A Cuomo

    Broad Institute, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5778-960X
  10. Sheng Sun

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2895-1153
  11. Joseph Heitman

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    For correspondence
    heitm001@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6369-5995
  12. Marco A Coelho

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    For correspondence
    marco.dias.coelho@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5716-0561

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

  1. Antonis Rokas, Vanderbilt University, United States

Publication history

  1. Preprint posted: March 30, 2022 (view preprint)
  2. Received: March 31, 2022
  3. Accepted: June 15, 2022
  4. Accepted Manuscript published: June 17, 2022 (version 1)
  5. 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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  1. Andrew Ryan Passer
  2. Shelly Applen Clancey
  3. Terrance Shea
  4. Márcia David-Palma
  5. Anna Floyd Averette
  6. Teun Boekhout
  7. Betina M Porcel
  8. Minou Nowrousian
  9. Christina A Cuomo
  10. Sheng Sun
  11. Joseph Heitman
  12. Marco A Coelho
(2022)
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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