Department of Biological Sciences, Vanderbilt University.
Department of Microbiology and Immunology, University of California San Francisco.
Genome Biol Evol. 2020 Jul 1;12(7):1119-1130. doi: 10.1093/gbe/evaa107.
Gene regulatory networks (GRNs) drive developmental and cellular differentiation, and variation in their architectures gives rise to morphological diversity. Pioneering studies in Aspergillus fungi, coupled with subsequent work in other filamentous fungi, have shown that the GRN governed by the BrlA, AbaA, and WetA proteins controls the development of the asexual fruiting body or conidiophore. A specific aspect of conidiophore development is the production of phialides, conidiophore structures that are under the developmental control of AbaA and function to repetitively generate spores. Fungal genome sequencing has revealed that some filamentous fungi lack abaA, and also produce asexual structures that lack phialides, raising the hypothesis that abaA loss is functionally linked to diversity in asexual fruiting body morphology. To examine this hypothesis, we carried out an extensive search for the abaA gene across 241 genomes of species from the fungal subphylum Pezizomycotina. We found that abaA was independently lost in four lineages of Eurotiomycetes, including from all sequenced species within the order Onygenales, and that all four lineages that have lost abaA also lack the ability to form phialides. Genetic restoration of abaA from Aspergillus nidulans into Histoplasma capsulatum, a pathogenic species from the order Onygenales that lacks an endogenous copy of abaA, did not alter Histoplasma conidiation morphology but resulted in a marked increase in spore viability. We also discovered that species lacking abaA contain fewer AbaA binding motifs in the regulatory regions of orthologs of some AbaA target genes, suggesting that the asexual fruiting body GRN of organisms that have lost abaA has likely been rewired. Our results provide an illustration of how repeated losses of a key regulatory transcription factor have contributed to the diversity of an iconic fungal morphological trait.
基因调控网络 (GRN) 驱动着发育和细胞分化，其结构的变异导致了形态多样性的产生。在 Aspergillus 真菌中的开创性研究，以及随后在其他丝状真菌中的研究表明，由 BrlA、AbaA 和 WetA 蛋白控制的 GRN 控制着无性生殖体或分生孢子梗的发育。分生孢子梗发育的一个特定方面是产生分生孢子器，这是 AbaA 控制的分生孢子梗结构，其功能是重复产生孢子。真菌基因组测序表明，一些丝状真菌缺乏 abaA，并且也产生缺乏分生孢子器的无性结构，这提出了 abaA 缺失与无性生殖体形态多样性具有功能关联的假说。为了检验这一假说，我们在 Pezizomycotina 真菌亚门的 241 个物种的基因组中广泛搜索 abaA 基因。我们发现，abaA 在 Eurotiomycetes 的四个谱系中独立丢失，包括所有已测序的 Onygenales 目物种，并且失去 abaA 的所有四个谱系也缺乏形成分生孢子器的能力。将 abaA 从 Aspergillus nidulans 遗传恢复到 Histoplasma capsulatum（来自 Onygenales 目的致病性物种，缺乏内源性 abaA 拷贝）中，没有改变 Histoplasma 分生孢子形成的形态，但导致孢子活力显著增加。我们还发现，缺乏 abaA 的物种在一些 AbaA 靶基因的同源物的调控区中含有较少的 AbaA 结合基序，这表明失去 abaA 的生物体的无性生殖体 GRN 可能已经重新布线。我们的研究结果提供了一个例证，说明关键调节转录因子的重复丢失如何促进了标志性真菌形态特征的多样性。
