Sexual reproduction between partners of the same mating type in Cryptococcus neoformans

Abstract

Cryptococcus neoformans is a globally distributed human fungal pathogen that causes life-threatening meningoencephalitis in immunocompromised patients1. It has a defined sexual cycle involving haploid cells of α and a mating types2, yet the vast majority of environmental and clinical isolates are α (ref. 3). Sexual recombination is normally expected to occur between isolates of opposite mating type in organisms with two mating types (or sexes). How sexual reproductive potential can be maintained in an organism with a largely unisexual, nearly clonal population genetic structure is unknown. One clue, however, is that α strains undergo fruiting, a process that resembles sexual mating4 but is thought to be strictly mitotic and asexual. We report here that hallmarks of mating occur during fruiting, including diploidization and meiosis. Pheromone response pathway elements and the key meiotic regulator Dmc1 are required for efficient fruiting. Furthermore, fusion and meiosis can occur between non-isogenic α strains, enabling genetic exchange. These studies reveal how sexual reproduction can occur between partners of the same mating type. These findings have implications for the evolution of microbial pathogens, as well as for parthenogenesis, cell fusion events and transitions between self-fertilizing and outcrossing modes of reproduction observed in both fungi and other kingdoms.

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Figure 1: Diploidization during monokaryotic fruiting.
Figure 2: Pheromone response and meiotic components promote fruiting.
Figure 3: Sexual recombination through mating or fruiting.

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Acknowledgements

We thank W.-C. Shen for strains, A. Mitchell, J. Fraser and A. Idnurm for discussions, and T. Mitchell, D. Lew, B. Capel, R. Wharton and J. Anderson for critical reading. This work was supported by an NIAID R01 grant to J.H. C.M.H. was supported by a Damon Runyon Cancer Research Fellowship and a Burroughs Wellcome Career Development Award in the Biomedical Sciences. J.H. is a Burroughs Wellcome Fund Scholar in Molecular Pathogenic Mycology and an Investigator of the Howard Hughes Medical Institute.

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Correspondence to Xiaorong Lin or Joseph Heitman.

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Supplementary Notes

This file contains Supplementary Data, Supplementary Methods, Supplementary Figure Legend and additional references. (DOC 41 kb)

Supplementary Figure S1

Dikaryotic mating hyphae contain two nuclei per compartment that alternate position at each conjugate division. (PDF 23 kb)

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Lin, X., Hull, C. & Heitman, J. Sexual reproduction between partners of the same mating type in Cryptococcus neoformans. Nature 434, 1017–1021 (2005). https://doi.org/10.1038/nature03448

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