Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex
Andrew Ryan Passer,
Shelly Applen Clancey,
Terrance Shea,
Márcia David-Palma,
Anna Floyd Averette,
Teun Boekhout,
Betina M Porcel,
Minou Nowrousian,
Christina A Cuomo,
Sheng Sun,
Joseph Heitman,
Marco A Coelho
Affiliations
Andrew Ryan Passer
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Shelly Applen Clancey
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Terrance Shea
Broad Institute of MIT and Harvard, Cambridge, United States
Márcia David-Palma
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Anna Floyd Averette
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
Teun Boekhout
Westerdijk Fungal Biodiversity Institute, Utrecht, Netherlands; Institute of Biodiversity and Ecosystem Dynamics (IBED), University of Amsterdam, Amsterdam, Netherlands
Betina M Porcel
Génomique Métabolique, CNRS, University Evry, Université Paris-Saclay, Evry, France
Sexual reproduction is a ubiquitous, ancient eukaryotic trait. While most sexual organisms have to find a mating partner, species as diverse as animals, plants, and fungi have evolved the ability to reproduce sexually without requiring another individual. Here, we uncovered the mechanism of self-compatibility (homothallism) in Cryptococcus depauperatus, a fungal species closely related to the human fungal pathogens Cryptococcus neoformans and Cryptococcus gattii. In contrast to C. neoformans or C. gattii, which grow as a yeast asexually, and produce hyphae, basidia, and infectious spores during sexual reproduction, C. depauperatus grows exclusively as hyphae decorated with basidia and abundant spores, thus continuously engaged in sexual reproduction. Through comparative genomics and analyses of mutants defective in key mating/meiosis genes, we demonstrate the C. depauperatus sexual cycle involves meiosis and that self-compatibility is orchestrated by an unlinked mating receptor (Ste3a) and pheromone ligand (MFα) pair 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 MATa alleles of other species, and a few MATα gene alleles scattered throughout the genome, but no homologs of the mating-type homeodomain genes SXI1 (HD1) and SXI2 (HD2). Comparative analyses suggest 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 fungus and provide insight into repeated transitions between sexual reproduction modes that have occurred throughout the fungal kingdom.
