scholarly journals Elucidation of the determinant for orchestration of solo unisexual cycle in an important human fungal pathogen

2019 ◽  
Author(s):  
Pengjie Hu ◽  
Huimin Liu ◽  
Lei Chen ◽  
Guang-Jun He ◽  
Xiuyun Tian ◽  
...  

AbstractIn fungi, the sex-determination program universally directs sexual development and syngamy (the fusion of gametes) that underlies pre-meiotic diploidization. However, the contribution of sex-determination to syngamy-independent sexual cycle, which requires autopolyploidization as an alternative approach to elevate ploidy before meiosis, remains unclear in fungi and other eukaryotes. The human fungal pathogen Cryptococcus neoformans, as a model organism for studying fungal sexual reproduction, can undergo syngamy-dependent bisexual and syngamy-independent solo unisexual reproduction, in which endoreplication is considered to enable pre-meiotic self-diploidization. Here, by characterizing a mutant lacking all the core sex-determination factors, we show that sex-determination plays a central role in bisexual syngamy but is not strictly required for unisexual development and self-diploidization. This implies an unknown circuit, rather than the sex-determination program, for specifically coordinating Cryptococcus unisexual cycle. We reveal that syngamy and self-diploidization are both governed by the Qsp1-directed paracrine system via two regulatory branches, Vea2 and Cqs2. Vea2 directs bisexual syngamy through the sex-determination program; conversely, Cqs2 is dispensable for bisexual syngamy but activates unisexual endoreplication. Through functional profiling of 41 transcription factors documented to regulate Cryptococcus sexual development, we reveal that only Cqs2 can drive and integrate all unisexual phases and ensure the production of meiospore progenies. Furthermore, ChIP-seq analysis together with genetic evaluation indicate that Cqs2 induces unisexual self-diploidization through its direct control of PUM1, whose expression is sufficient to drive autopolyploidization. Therefore, Cqs2 serves as the critical determinant that orchestrates Cryptococcus multistage unisexual cycle that does not strictly require the sexual-determination program.

2005 ◽  
Vol 4 (3) ◽  
pp. 526-535 ◽  
Author(s):  
Christina M. Hull ◽  
Marie-Josee Boily ◽  
Joseph Heitman

ABSTRACT Homeodomain proteins are central regulators of development in eukaryotes. In fungi, homeodomain proteins have been shown to control cell identity and sexual development. Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle that produces spores, the suspected infectious particles. Previously, only a single homeodomain regulatory protein involved in sexual development, Sxi1α, had been identified. Here we present the discovery of Sxi2a, a predicted but heretofore elusive cell-type-specific homeodomain protein essential for the regulation of sexual development. Our studies reveal that Sxi2a is necessary for proper sexual development and sufficient to drive this development in otherwise haploid α cells. We further show that Sxi1α and Sxi2a interact with one another and impart similar expression patterns for two key mating genes. The discovery of Sxi2a and its relationship with Sxi1α leads to a new model for how the sexual cycle is controlled in C. neoformans, with implications for virulence.


2003 ◽  
Vol 2 (5) ◽  
pp. 1036-1045 ◽  
Author(s):  
James A. Fraser ◽  
Ryan L. Subaran ◽  
Connie B. Nichols ◽  
Joseph Heitman

ABSTRACT Cryptococcus neoformans is a human fungal pathogen that exists as three distinct varieties or sibling species: the predominantly opportunistic pathogens C. neoformans var. neoformans (serotype D) and C. neoformans var. grubii (serotype A) and the primary pathogen C. neoformans var. gattii (serotypes B and C). While serotypes A and D are cosmopolitan, serotypes B and C are typically restricted to tropical regions. However, serotype B isolates of C. neoformans var. gattii have recently caused an outbreak on Vancouver Island in Canada, highlighting the threat of this fungus and its capacity to infect immunocompetent individuals. Here we report a large-scale analysis of the mating abilities of serotype B and C isolates from diverse sources and identify unusual strains that mate robustly and are suitable for further genetic analysis. Unlike most isolates, which are of both the a and α mating types but are predominantly sterile, the majority of the Vancouver outbreak strains are exclusively of the α mating type and the majority are fertile. In an effort to enhance mating of these isolates, we identified and disrupted the CRG1 gene encoding the GTPase-activating protein involved in attenuating pheromone response. crg1 mutations dramatically increased mating efficiency and enabled mating with otherwise sterile isolates. Our studies provide a genetic and molecular foundation for further studies of this primary pathogen and reveal that the Vancouver Island outbreak may be attributable to a recent recombination event.


2007 ◽  
Vol 1 (4) ◽  
pp. 263-273 ◽  
Author(s):  
Chaoyang Xue ◽  
Yasuomi Tada ◽  
Xinnian Dong ◽  
Joseph Heitman

2021 ◽  
Vol 7 (10) ◽  
pp. 858
Author(s):  
Jiao-yu Wang ◽  
Shi-zhen Wang ◽  
Zhen Zhang ◽  
Zhong-na Hao ◽  
Xiao-xiao Shi ◽  
...  

Magnaporthe oryzae, a fungal pathogen that causes rice blast, which is the most destructive disease of rice worldwide, has the potential to perform both asexual and sexual reproduction. MAT loci, consisting of MAT genes, were deemed to determine the mating types of M. oryzae strains. However, investigation was rarely performed on the development and molecular mechanisms of the sexual reproduction of the fungus. In the present work, we analyzed the roles of two MAT loci and five individual MAT genes in the sex determination, sexual development and pathogenicity of M. oryzae. Both of the MAT1-1 and MAT1-2 loci are required for sex determination and the development of sexual structures. MAT1-1-1, MAT1-1-3 and MAT1-2-1 genes are crucial for the formation of perithecium. MAT1-1-2 impacts the generation of asci and ascospores, while MAT1-2-2 is dispensable for sexual development. A GFP fusion experiment indicated that the protein of MAT1-1-3 is distributed in the nucleus. However, all of the MAT loci or MAT genes are dispensable for vegetative growth, asexual reproduction, pathogenicity and pathogenicity-related developments of the fungus, suggesting that sexual reproduction is regulated relatively independently in the development of the fungus. The data and methods of this work may be helpful to further understand the life cycle and the variation of the fungus.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
María Gabián ◽  
Paloma Morán ◽  
Ana I. Fernández ◽  
Beatriz Villanueva ◽  
Amel Chtioui ◽  
...  

Abstract Background A complete understanding of the genetic basis for sexual determination and differentiation is necessary in order to implement efficient breeding schemes at early stages of development. Atlantic salmon belongs to the family Salmonidae of fishes and represents a species of great commercial value. Although the species is assumed to be male heterogametic with XY sex determination, the precise genetic basis of sexual development remains unclear. The complexity is likely associated to the relatively recent salmonid specific whole genome duplication that may be responsible for certain genome instability. This instability together with the capacity of the sex-determining gene to move across the genome as reported by previous studies, may explain that sexual development genes are not circumscribed to the same chromosomes in all members of the species. In this study, we have used a 220 K SNP panel developed for Atlantic salmon to identify the chromosomes explaining the highest proportion of the genetic variance for sex as well as candidate regions and genes associated to sexual development in this species. Results Results from regional heritability analysis showed that the chromosomes explaining the highest proportion of variance in these populations were Ssa02 (heritability = 0.42, SE = 0.12) and Ssa21 (heritability = 0.26, SE = 0.11). After pruning by linkage disequilibrium, genome-wide association analyses revealed 114 SNPs that were significantly associated with sex, being Ssa02 the chromosome containing a greatest number of regions. Close examination of the candidate regions evidenced important genes related to sex in other species of Class Actinopterygii, including SDY, genes from family SOX, RSPO1, ESR1, U2AF2A, LMO7, GNRH-R, DND and FIGLA. Conclusions The combined results from regional heritability analysis and genome-wide association have provided new advances in the knowledge of the genetic regulation of sex determination in Atlantic salmon, supporting that Ssa02 is the candidate chromosome for sex in this species and suggesting an alternative population lineage in Spanish wild populations according to the results from Ssa21.


2008 ◽  
Vol 7 (10) ◽  
pp. 1724-1732 ◽  
Author(s):  
Verena Große ◽  
Sven Krappmann

ABSTRACT The major fungal pathogen of humans, Aspergillus fumigatus, lacks a defined sexual cycle, although the presence of genes encoding putative mating type idiomorphs and regulators of Aspergillus sexual development heightens the potential for cryptic sexuality in this deuteromycete. To test the functionality of these genetic determinants, we transferred the alpha box-encoding mat1-1 idiomorph from an A. fumigatus isolate to the homothallic fertile species Aspergillus nidulans. Abundant formation of fruiting bodies (cleistothecia) containing viable ascospores establishes functionality of this mating type gene product in the transgenic strain. Using a similar approach, we also established that the conserved transcriptional regulator from A. fumigatus, the nsdD gene product, can act as a functional, positively acting factor for A. nidulans cleistothecium development; moreover, high-level expression of NsdD in the endogenous host A. fumigatus profoundly alters hyphal development by triggering the formation of coiled hyphae. Our findings demonstrate that the presumably asexual pathogen A. fumigatus encodes functional regulators of mating and sexual development, thereby potentiating the case for cryptic sexuality in this fungal pathogen.


2008 ◽  
Vol 74 (20) ◽  
pp. 6248-6253 ◽  
Author(s):  
Cory R. Kent ◽  
Patricia Ortiz-Bermúdez ◽  
Steven S. Giles ◽  
Christina M. Hull

ABSTRACT For over 3 decades, sexual development in the human fungal pathogen Cryptococcus neoformans and other fungi has been initiated by growing compatible mating partners on V8 juice medium. Although this medium is an efficient inducer of sexual development, the mechanism by which it promotes the process is unknown. To understand how V8 juice medium induces sexual development, we attempted to purify inducing factors from V8 juice, and we carried out a complete compositional analysis of V8 juice. We discovered that no single factor is responsible for the effects of V8 juice medium. Rather, the unique composition of V8 juice medium provides the proper nutrient composition for inducing and sustaining complete sexual development. Utilizing these findings, we developed a defined V8 (DV8) medium that mimics V8 juice medium in sexual development assays. Then, using DV8 as a tool, we explored the roles that specific molecules play in enhancing sexual development. Surprisingly, we discovered that copper is a key factor, leading to an upregulation of the mating pheromone genes MF a and MFα, both required for the initial steps in sexual development. The utilization of DV8 to investigate the effects of copper on sexual development presented here is an example of how defining the conditions that induce sexual development will advance the study of C. neoformans.


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