| Title: | The Pheromone and Pheromone Receptor Mating-Type Locus Is Involved in Controlling Uniparental Mitochondrial Inheritance in Cryptococcus |
| Author(s): | Sun S; Fu C; Ianiri G; Heitman J; |
| Address: | "Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710 heitm001@duke.edu" |
| DOI: | 10.1534/genetics.119.302824 |
| ISSN/ISBN: | 1943-2631 (Electronic) 0016-6731 (Print) 0016-6731 (Linking) |
| Abstract: | "Mitochondria are inherited uniparentally during sexual reproduction in the majority of eukaryotic species studied, including humans, mice, and nematodes, as well as many fungal species. Mitochondrial uniparental inheritance (mito-UPI) could be beneficial in that it avoids possible genetic conflicts between organelles with different genetic backgrounds, as recently shown in mice, and it could prevent the spread of selfish genetic elements in the mitochondrial genome. Despite the prevalence of observed mito-UPI, the underlying mechanisms and the genes involved in controlling this non-Mendelian inheritance are poorly understood in many species. In Cryptococcus neoformans, a human pathogenic basidiomyceteous fungus, mating types (MATalpha and MATa) are defined by alternate alleles at the single MAT locus that evolved from fusion of the two MAT loci (P/R encoding pheromones and pheromone receptors, and HD encoding homeodomain transcription factors) that are the ancestral state in the basidiomycota. Mitochondria are inherited uniparentally from the MATa parent in C. neoformans, and this requires the SXI1alpha and SXI2a HD factors encoded by MAT However, there is evidence that additional genes contribute to the control of mito-UPI in Cryptococcus Here, we show that in C. amylolentus, a sibling species of C. neoformans with unlinked P/R and HD MAT loci, mito-UPI is controlled by the P/R locus and is independent of the HD locus. Consistently, by replacing the MATalpha alleles of the pheromones (MF) and pheromone receptor (STE3) with the MATa alleles, we show that these P/R locus-defining genes indeed affect mito-UPI in C. neoformans during sexual reproduction. Additionally, we show that during early stages of C. neoformans sexual reproduction, conjugation tubes are always produced by the MATalpha cells, resulting in unidirectional migration of the MATalpha nucleus into the MATa cell during zygote formation. This process is controlled by the P/R locus and could serve to physically restrict movement of MATalpha mitochondria in the zygotes, and thereby contribute to mito-UPI. We propose a model in which both physical and genetic mechanisms function in concert to prevent the coexistence of mitochondria from the two parents in the zygote, and subsequently in the meiotic progeny, thus ensuring mito-UPI in pathogenic Cryptococcus, as well as in closely related nonpathogenic species. The implications of these findings are discussed in the context of the evolution of mito-UPI in fungi and other more diverse eukaryotes" |
| Keywords: | "Cryptococcus neoformans/*genetics/pathogenicity Evolution, Molecular Fungal Proteins/genetics Genes, Mating Type, Fungal/*genetics Humans Mitochondria *Pheromones Receptors, Pheromone/*genetics Reproduction/genetics Cryptococcus fungi mitochondrial unipar;" |
| Notes: | "MedlineSun, Sheng Fu, Ci Ianiri, Giuseppe Heitman, Joseph eng R01 AI050113/AI/NIAID NIH HHS/ R01 AI133654/AI/NIAID NIH HHS/ R37 AI039115/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural 2020/01/01 Genetics. 2020 Mar; 214(3):703-717. doi: 10.1534/genetics.119.302824. Epub 2019 Dec 30" |
