Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis.
Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis.
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DOI：
10.1371/journal.pbio.2003769
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发表时间：
2017-09
期刊：
影响因子：
9.8
通讯作者：
Roger AJ
中科院分区：
文献类型：
--
作者：
Gentekaki E;Curtis BA;Stairs CW;Klimeš V;Eliáš M;Salas-Leiva DE;Herman EK;Eme L;Arias MC;Henrissat B;Hilliou F;Klute MJ;Suga H;Malik SB;Pightling AW;Kolisko M;Rachubinski RA;Schlacht A;Soanes DM;Tsaousis AD;Archibald JM;Ball SG;Dacks JB;Clark CG;van der Giezen M;Roger AJ
芽囊原虫是人类肠道中最常见的真核微生物，全球约有10亿人感染。虽然芽囊原虫与肠道疾病有关，但其致病性仍有争议，因为大多数携带者无症状。在这里，芽囊原虫亚型（ST）1的基因组序列，并与先前公布的ST 4和ST 7的序列进行比较。尽管保守的核心基因，有意想不到的多样性，这些ST在其基因组大小，鸟嘌呤胞嘧啶（GC）的内容，内含子的数量，和基因的内容。ST 1有6，544个蛋白质编码基因，比ST 4和ST 7多几百个。每个ST所特有的蛋白质的百分比范围从6.2%到20.5%，大大超过了寄生虫属内观察到的差异。Orthopathy蛋白在ST之间的氨基酸序列同一性上也显示出极端的差异（即，59%-61%的中位数同一性），与寄生虫属的最远相关物种对的观察结果相同。ST在基因家族分布和大小上也显示出很大的差异，特别是蛋白激酶和蛋白酶基因家族，这可能反映了毒力的差异。这些ST间差异在ST内水平上持续到何种程度还有待观察。ST 1中有26%的基因具有终止密码子，这些终止密码子是通过仅在囊胚中发现的新型多聚腺苷酸化机制在mRNA水平上产生的。途径和细胞器系统的重建显示，ST 1有一个相对完整的膜运输系统和一个接近完整的减数分裂工具包，可能表明性周期。与一些肠道原生生物寄生虫不同，芽囊原虫ST 1具有几乎完全的从头嘧啶、嘌呤和硫胺素生物合成途径，并且在所研究的斯特拉氏菌中是独特的，能够代谢α-葡聚糖而不是β-葡聚糖。它缺乏编码含血红素的细胞色素P450蛋白的所有基因。对线粒体相关细胞器（MRO）蛋白质组的预测揭示了一个扩展的功能库，包括脂质、辅因子和维生素生物合成，以及可能参与调节线粒体形态和MRO/内质网（ER）相互作用的蛋白质。与此形成鲜明对比的是，过氧化物酶体相关功能的基因是不存在的，这表明芽囊原虫ST缺乏这种细胞器。总的来说，这项研究为了解芽囊原虫的生物学提供了一个重要的窗口，展示了ST之间的显著差异，可以指导未来对其毒力差异的实验研究，并阐明这些生物体在肠道健康和疾病中的作用。芽囊原虫是一种与藻类和某些植物病原体相关的单细胞真核生物。它们是人类肠道微生物群落的常见组成部分，在全世界约有10亿人定居。他们的存在是否有害仍在激烈辩论中。不确定性的部分原因是，至少有17个亚型已被确定从各种哺乳动物宿主，包括9个从人类。为了更好地表征和理解囊胚，我们对亚型1的基因组进行了测序和注释，并将其与以前亚型7和4的基因组结果进行了比较。比较显示，3个测序亚型之间的许多基因组特征，如DNA碱基组成，基因组大小，基因数量和内含子数量有相当大的差异。我们还在完整基因互补的背景下检查了各种生化途径和细胞系统，以更好地了解囊胚的生物学，包括一些更不寻常的特征，如与囊胚相关的细胞器。我们还确定了亚型特异性基因家族的扩展，可能与毒力。最后，我们发现，芽囊原虫似乎拥有有性生殖所需的大部分基因。这项研究为未来研究这些常见肠道微生物的生物学和潜在致病性提供了资源和假设。
Blastocystis is the most prevalent eukaryotic microbe colonizing the human gut, infecting approximately 1 billion individuals worldwide. Although Blastocystis has been linked to intestinal disorders, its pathogenicity remains controversial because most carriers are asymptomatic. Here, the genome sequence of Blastocystis subtype (ST) 1 is presented and compared to previously published sequences for ST4 and ST7. Despite a conserved core of genes, there is unexpected diversity between these STs in terms of their genome sizes, guanine-cytosine (GC) content, intron numbers, and gene content. ST1 has 6,544 protein-coding genes, which is several hundred more than reported for ST4 and ST7. The percentage of proteins unique to each ST ranges from 6.2% to 20.5%, greatly exceeding the differences observed within parasite genera. Orthologous proteins also display extreme divergence in amino acid sequence identity between STs (i.e., 59%–61% median identity), on par with observations of the most distantly related species pairs of parasite genera. The STs also display substantial variation in gene family distributions and sizes, especially for protein kinase and protease gene families, which could reflect differences in virulence. It remains to be seen to what extent these inter-ST differences persist at the intra-ST level. A full 26% of genes in ST1 have stop codons that are created on the mRNA level by a novel polyadenylation mechanism found only in Blastocystis. Reconstructions of pathways and organellar systems revealed that ST1 has a relatively complete membrane-trafficking system and a near-complete meiotic toolkit, possibly indicating a sexual cycle. Unlike some intestinal protistan parasites, Blastocystis ST1 has near-complete de novo pyrimidine, purine, and thiamine biosynthesis pathways and is unique amongst studied stramenopiles in being able to metabolize α-glucans rather than β-glucans. It lacks all genes encoding heme-containing cytochrome P450 proteins. Predictions of the mitochondrion-related organelle (MRO) proteome reveal an expanded repertoire of functions, including lipid, cofactor, and vitamin biosynthesis, as well as proteins that may be involved in regulating mitochondrial morphology and MRO/endoplasmic reticulum (ER) interactions. In sharp contrast, genes for peroxisome-associated functions are absent, suggesting Blastocystis STs lack this organelle. Overall, this study provides an important window into the biology of Blastocystis, showcasing significant differences between STs that can guide future experimental investigations into differences in their virulence and clarifying the roles of these organisms in gut health and disease. Blastocystis are unicellular eukaryotic organisms related to algae and some plant pathogens. They are common constituents of the human gut microbial community, colonizing approximately 1 billion humans worldwide. Whether their presence is harmful or not continues to be hotly debated. Part of the uncertainty stems from the fact that at least 17 subtypes have been identified from various mammalian hosts, including 9 from humans. To better characterize and understand Blastocystis, we have sequenced and annotated the genome for subtype 1 and compared it with previous genomic results for subtypes 7 and 4. The comparisons revealed considerable differences between the 3 sequenced subtypes for a number of genomic features like DNA base composition, size of genome, number of genes, and number of introns. We also examined various biochemical pathways and cellular systems in the context of the full gene complement to better understand the biology of Blastocystis, including some of its more unusual features like a mitochondrion related organelle. We also identified subtype-specific gene family expansions that may be related to virulence. Finally, we showed that Blastocystis appears to have most of the genes necessary for sexual reproduction. This study provides resources and hypotheses for future investigations into the biology and potential pathogenicity of these common gut microbes.
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