a Genetics, Genomics and Systems Biology, School of BioSciences , University of Melbourne , Australia.
b School of Biotechnology and Biomolecular Sciences , University of New South Wales , Sydney , Australia.
Virulence. 2019 Dec;10(1):277-291. doi: 10.1080/21505594.2019.1593776.
Aspartyl proteases are a widely represented class of proteolytic enzymes found in eukaryotes and retroviruses. They have been associated with pathogenicity in a range of disease-causing microorganisms. The dimorphic human-pathogenic fungus Talaromyces marneffei has a large expansion of these proteases identified through genomic analyses. Here we characterize the expansion of these genes (pop - paralogue of pep) and their role in T. marneffei using computational and molecular approaches. Many of the genes in this monophyletic family show copy number variation and positive selection despite the preservation of functional regions and possible redundancy. We show that the expression profile of these genes differs and some are expressed during intracellular growth in the host. Several of these proteins have distinctive localization as well as both additive and epistatic effects on the formation of yeast cells during macrophage infections. The data suggest that this is a recently evolved aspartyl protease gene family which affects intracellular growth and contributes to the pathogenicity of T. marneffei.
天冬氨酸蛋白酶是一类广泛存在于真核生物和逆转录病毒中的蛋白水解酶，与多种致病微生物的致病性有关。二相性人致病性真菌马尔尼菲篮状菌通过基因组分析鉴定出这些蛋白酶的大量扩增。在这里，我们使用计算和分子方法来描述这些基因（pop- pep 的旁系同源物）的扩增及其在 T. marneffei 中的作用。尽管保留了功能区域和可能的冗余，但这个单系家族中的许多基因显示出拷贝数变异和正选择。我们表明，这些基因的表达谱不同，并且一些基因在宿主细胞内生长期间表达。这些蛋白中的一些具有独特的定位，并且在巨噬细胞感染期间对酵母细胞的形成具有累加和上位效应。这些数据表明，这是一个最近进化的天冬氨酸蛋白酶基因家族，它影响细胞内生长并有助于 T. marneffei 的致病性。
