Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.
Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.
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DOI：
10.1186/1471-2164-11-510
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发表时间：
2010-09-23
期刊：
影响因子：
4.4
通讯作者：
Cardenas ME
中科院分区：
文献类型：
--
作者：
Shertz CA;Bastidas RJ;Li W;Heitman J;Cardenas ME
营养感应Tor途径控制细胞生长，并且在从单细胞酵母到多细胞生物（包括人类）的几乎所有真核生物中保守。Tor是免疫抑制药物雷帕霉素的靶标，雷帕霉素与脯氨酰异构酶FKBP 12复合抑制Tor功能。雷帕霉素是1999年FDA批准的器官移植受者的金标准药物，并且正在寻找作为化疗和抗增殖剂的其他临床适应症。利用大量最近测序的基因组，我们进行了比较基因组研究，以注释Tor途径在整个真菌王国和相关的单细胞后鞭毛体，包括Monosiga brevicollis，Salpingoeca rosetta和Capsaspora owczarzaki。有趣的是，Tor信号级联在三种具有可用基因组序列的微孢子虫物种中不存在，这是缺乏这种保守途径的真核生物群的唯一已知实例。微孢子虫是专性细胞内病原体，基因组高度减少，我们假设它们失去了Tor途径，因为它们适应和精简了它们的基因组，以便在营养丰富的环境中进行细胞内生长。两个TOR旁系同源物存在于几种真菌物种中，作为全基因组复制或独立基因/片段复制事件的结果。其中一个事件是在两栖类病原体Batrachochytrium dendrobaerum中发现的，这是一种导致全球两栖类减少和灭绝的壶菌。真菌界中TOR基因的重复独立复制可能反映了作用于这种激酶的选择性压力，这种激酶占据了两种具有不同细胞作用的蛋白质复合物。这些比较基因组分析说明了一个中央营养感应级联的进化轨迹，使不同的真核生物对自然环境作出反应。
The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki. Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions. The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural environments.
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影响因子：
16
作者：
Adami, Alessandra;Garcia-Alvarez, Begona;Llorca, Oscar
通讯作者：
Llorca, Oscar
影响因子：
2.2
作者：
Cushion, MT
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Sonnhammer, ELL
DOI：
10.1073/pnas.0400975101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Boussau, B;Karlberg, EO;Andersson, SGE
通讯作者：
Andersson, SGE