Bian Zhuyun, Xu Ziyan, Peer Anushka, Choi Yeseul, Priest Shelby J, Akritidou Konstantina, Dasgupta Ananya, Dahlmann Tim A, Kück Ulrich, Nowrousian Minou, Sachs Matthew S, Sun Sheng, Heitman Joseph
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA.
Department of Biology, Texas A&M University, College Station, Texas, USA.
bioRxiv. 2024 Dec 5:2024.12.02.626420. doi: 10.1101/2024.12.02.626420.
Fungal sexual reproduction is controlled by the mating-type () locus. In contrast to a majority of species in the phylum Basidiomycota that have tetrapolar mating-type systems, the opportunistic human pathogen employs a bipolar mating-type system, with two mating types ( and α) determined by a single locus that is unusually large (~120 kb) and contains more than 20 genes. While several genes are associated with mating and sexual development, others control conserved cellular processes (e.g. cargo transport and protein synthesis), of which five (, , , , and ) have been hypothesized to be essential. In this study, through genetic analysis involving sporulation of heterozygous diploid deletion mutants, as well as in some cases construction and analyses of conditional expression alleles of these genes, we confirmed that with the exception of , both alleles of the other four genes are indeed essential for cell viability. We further showed that while is not essential, its function is critical for infectious spore production, faithful cytokinesis, adaptation for growth at high temperature, and pathogenicity . Our results demonstrate the presence of essential genes in the locus that are divergent between cells of opposite mating types. We discuss possible mechanisms to maintain functional alleles of these essential genes in a rapidly-evolving genomic region in the context of fungal sexual reproduction and mating-type evolution.
真菌有性生殖由交配型()位点控制。与担子菌门中大多数具有四极性交配型系统的物种不同,机会性人类病原体采用双极性交配型系统,有两种交配型(和α),由一个异常大(约120 kb)且包含20多个基因的单个位点决定。虽然几个基因与交配和有性发育相关,但其他基因控制保守的细胞过程(如货物运输和蛋白质合成),其中五个(、、、和)被推测为必需基因。在本研究中,通过涉及杂合二倍体缺失突变体孢子形成的遗传分析,以及在某些情况下构建和分析这些基因的条件表达等位基因,我们证实除了外,其他四个基因的两个等位基因确实对细胞活力至关重要。我们进一步表明,虽然不是必需的,但其功能对于感染性孢子产生、忠实的胞质分裂、适应高温生长和致病性至关重要。我们的结果证明在交配型相反的细胞之间存在差异的位点中存在必需基因。我们讨论了在真菌有性生殖和交配型进化的背景下,在快速进化的基因组区域中维持这些必需基因功能等位基因的可能机制。