Razavi Newman Center for Bioinformatics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Genome Biol. 2011 Jul 25;12(7):R66. doi: 10.1186/gb-2011-12-7-r66.
The major human intestinal pathogen Giardia lamblia is a very early branching eukaryote with a minimal genome of broad evolutionary and biological interest.
To explore early kinase evolution and regulation of Giardia biology, we cataloged the kinomes of three sequenced strains. Comparison with published kinomes and those of the excavates Trichomonas vaginalis and Leishmania major shows that Giardia's 80 core kinases constitute the smallest known core kinome of any eukaryote that can be grown in pure culture, reflecting both its early origin and secondary gene loss. Kinase losses in DNA repair, mitochondrial function, transcription, splicing, and stress response reflect this reduced genome, while the presence of other kinases helps define the kinome of the last common eukaryotic ancestor. Immunofluorescence analysis shows abundant phospho-staining in trophozoites, with phosphotyrosine abundant in the nuclei and phosphothreonine and phosphoserine in distinct cytoskeletal organelles. The Nek kinase family has been massively expanded, accounting for 198 of the 278 protein kinases in Giardia. Most Neks are catalytically inactive, have very divergent sequences and undergo extensive duplication and loss between strains. Many Neks are highly induced during development. We localized four catalytically active Neks to distinct parts of the cytoskeleton and one inactive Nek to the cytoplasm.
The reduced kinome of Giardia sheds new light on early kinase evolution, and its highly divergent sequences add to the definition of individual kinase families as well as offering specific drug targets. Giardia's massive Nek expansion may reflect its distinctive lifestyle, biphasic life cycle and complex cytoskeleton.
人类主要肠道病原体蓝氏贾第鞭毛虫是一种非常早期分支的真核生物，具有广泛的进化和生物学意义的最小基因组。
为了探索早期激酶的进化和调控贾第虫生物学，我们对三个已测序的菌株的激酶组进行了编目。与已发表的激酶组以及挖掘的阴道毛滴虫和利什曼原虫的激酶组进行比较表明，贾第虫的 80 个核心激酶构成了任何可在纯培养中生长的真核生物中已知的最小核心激酶组，反映了其早期起源和二次基因丢失。在 DNA 修复、线粒体功能、转录、剪接和应激反应中的激酶丢失反映了这种减少的基因组，而其他激酶的存在有助于定义最后的共同真核祖先的激酶组。免疫荧光分析显示滋养体中存在丰富的磷酸化染色，核中富含磷酸酪氨酸，而磷酸苏氨酸和磷酸丝氨酸则存在于不同的细胞骨架细胞器中。Nek 激酶家族已经大规模扩张，占贾第虫 278 种蛋白激酶中的 198 种。大多数 Nek 是无催化活性的，序列差异很大，并且在菌株之间发生广泛的重复和丢失。许多 Nek 在发育过程中高度诱导。我们将四个具有催化活性的 Nek 定位于细胞骨架的不同部位，一个无活性的 Nek 定位于细胞质。
贾第虫的简化激酶组为早期激酶进化提供了新的线索，其高度分化的序列不仅增加了单个激酶家族的定义，还提供了特定的药物靶点。贾第虫的大规模 Nek 扩张可能反映了其独特的生活方式、二相生命周期和复杂的细胞骨架。
