Analysis of Pneumocystis Transcription Factor Evolution and Implications for Biology and Lifestyle.

Analysis of Pneumocystis Transcription Factor Evolution and Implications for Biology and Lifestyle.
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DOI:
10.1128/mbio.02711-22
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发表时间:
2023-02-28
期刊:
影响因子:
6.4
通讯作者:
--
中科院分区:
生物学1区
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--
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杰罗夫西氏肺孢子虫每年导致数十万免疫功能低下的患者死亡。然而,这种专性病原体的生物学的许多方面仍然不清楚,因为不可能在体外独立于宿主培养这种真菌。因此,我们对肺孢子虫病原学的理解在很大程度上依赖于生物信息学的推断。我们已经利用基因组和系统发育的强大组合方法来研究肺孢子虫物种中转录因子的进化。我们选择了与转录调控因子相对应的蛋白质家族(Pfam家族),并使用生物信息学方法将迄今已测序的七种肺孢子虫中的这些家族与其他酵母、其他人类和植物病原体以及其他专性寄生虫的家族进行了比较。一些Pfam转录因子家族在肺孢子虫属中的进化过程中经历了显著的减少,其他Pfam家族已经丢失或似乎正在丢失的过程中。与此同时,其他转录因子家族也被保留在肺孢子虫物种中,有些甚至似乎经历了扩张。在此基础上,肺孢子虫物种似乎保留了控制染色体维持、核糖体基因调控、RNA加工和修饰以及呼吸作用的转录调控因子。与此同时,促进替代碳源、氨基酸、脂肪和类固醇生物合成的同化,以及铁感应和动态平衡的调节似乎已经失去。我们对转录因子的保留、丢失和获得的分析为了解肺孢子虫的生物学和生活方式提供了重要的见解。
Pneumocystis jirovecii kills hundreds of thousands of immunocompromised patients each year. Yet many aspects of the biology of this obligate pathogen remain obscure because it is not possible to culture the fungus in vitro independently of its host. Consequently, our understanding of Pneumocystis pathobiology is heavily reliant upon bioinformatic inferences. We have exploited a powerful combination of genomic and phylogenetic approaches to examine the evolution of transcription factors in Pneumocystis species. We selected protein families (Pfam families) that correspond to transcriptional regulators and used bioinformatic approaches to compare these families in the seven Pneumocystis species that have been sequenced to date with those from other yeasts, other human and plant pathogens, and other obligate parasites. Some Pfam families of transcription factors have undergone significant reduction during their evolution in the Pneumocystis genus, and other Pfam families have been lost or appear to be in the process of being lost. Meanwhile, other transcription factor families have been retained in Pneumocystis species, and some even appear to have undergone expansion. On this basis, Pneumocystis species seem to have retained transcriptional regulators that control chromosome maintenance, ribosomal gene regulation, RNA processing and modification, and respiration. Meanwhile, regulators that promote the assimilation of alternative carbon sources, amino acid, lipid, and sterol biosynthesis, and iron sensing and homeostasis appear to have been lost. Our analyses of transcription factor retention, loss, and gain provide important insights into the biology and lifestyle of Pneumocystis.
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