The fungus Cryptococcus neoformans can undergo a -α bisexual and unisexual reproduction. Completion of both sexual reproduction modes requires similar cellular differentiation processes and meiosis. Although bisexual reproduction generates equal number of a and α progeny and is far more efficient than unisexual reproduction under mating-inducing laboratory conditions, the α mating type dominates in nature. Population genetic studies suggest that unisexual reproduction by α isolates might have contributed to this sharply skewed distribution of the mating types. However, the predominance of the α mating type and the seemingly inefficient unisexual reproduction observed under laboratory conditions present a conundrum. Here, we discovered a previously unrecognized condition that promotes unisexual reproduction while suppressing bisexual reproduction. Pheromone is the principal stimulus for bisexual development in Cryptococcus . Interestingly, pheromone and other components of the pheromone pathway, including the key transcription factor Mat2, are not necessary but rather inhibitory for Cryptococcus to complete its unisexual cycle under this condition. The inactivation of the pheromone pathway promotes unisexual reproduction despite the essential role of this pathway in non-self-recognition during bisexual reproduction. Nonetheless, the requirement for the known filamentation regulator Znf2 and the expression of hyphal or basidium specific proteins remain the same for pheromone-dependent or independent sexual reproduction. Transcriptome analyses and an insertional mutagenesis screen in mat2 Δ identified calcineurin being essential for this process. We further found that Znf2 and calcineurin work cooperatively in controlling unisexual development in this fungus. These findings indicate that Mat2 acts as a repressor of pheromone-independent unisexual development while serving as an activator for a -α bisexual development. The bi-functionality of Mat2 might have allowed it to act as a toggle switch for the mode of sexual development in this ubiquitous eukaryotic microbe. Author summary Like many higher eukaryotes, the fungus Cryptococcus neoformans is known to undergo bisexual mating that involves α and a partners. Surprisingly, the α mating type is dominant in nature (>99%). Unisexual reproduction was previously discovered in Cryptococcus and the mating type α allele enhances this sexual reproduction mode. However, bisexual mating is far more robust than unisexual development under all current laboratory conditions tested. This challenges the predicted prevalence and importance of unisexual development in cryptococcal population. In this study, we identified a condition that favors unisexual reproduction and suppresses bisexual reproduction. We showed that unisexual reproduction occurring under this condition is independent of pheromone or the key components of the pheromone pathway, despite the fact that this pathway is crucial for bisexual development. Our findings demonstrate that the pheromone pathway is primarily used for identifying compatible mating partners through non-self recognition, and it is not required for pheromone-independent unisexual reproduction. This discovery opens the door to investigate how this eukaryotic microbe specifies different modes of sexual reproduction and the bifurcation of genetic control of these reproduction modes.
【초록키워드】 Transcriptome, Population, Laboratory, Prevalence, Protein, inactivation, pathway, distribution, fungus, expression, cellular, microbe, transcription factor, Cryptococcus neoformans, independent of, sexual reproduction, bisexual reproduction, mating type, sexual development, mating types, opens, specific proteins, cellular differentiation, Bifurcation, skewed distribution, mode, favor, completion, allele, door, activator, component, hyphal, pheromone, meiosis, genetic study, repressor, calcineurin, Cryptococcus, genetic control, Znf2, higher eukaryotes, progeny, inhibitory, dominant, Complete, isolate, independent, robust, ENhance, tested, predicted, required, generate, undergo, condition, analysis, promote, Like, contributed, suppresse, conditions, inefficient, eukaryotic, Cryptococcus neoforman, differentiation processe, insertional mutagenesis, skewed, 【제목키워드】 independent,