Genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease.
Genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease.
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DOI：
10.1371/journal.pcbi.1002320
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发表时间：
2011-12
影响因子：
4.3
通讯作者：
Chen N
中科院分区：
文献类型：
--
作者：
Frech C;Chen N
疟原虫是疟疾的病原体，它们之间重要的表型差异背后的基因常常只在物种的一个子集中被发现，并聚集在染色体动态进化的亚端粒区域。我们假设疟原虫基因组的染色体内部区域含有额外的物种亚群特异性基因，这些基因是人类致病性、人际传播性和人类毒力差异的基础。我们将序列相似性搜索与synsynblock分析相结合，在6个已发表的疟原虫基因组的染色体内部区域鉴定出物种亚群特异性基因，包括恶性疟原虫、间日疟原虫、诺氏疟原虫、约利疟原虫、伯氏疟原虫和夏波疟原虫。为了改进比较分析，我们首先使用基于同源性的基因查找器修改了错误注释的基因模型，并在同构上下文中检查了假定的亚群特异性基因。然后分析已确认的亚群特异性基因在生物学途径中的作用，并使用公开可用的数据库检查其分子功能。我们发现了16个在三种灵长类寄生虫中保守性较好的基因，而在啮齿动物寄生虫中没有发现，其中包括3个硫胺素（维生素B1）生物合成途径的关键酶。在两种人类寄生虫中发现了13个基因，但在猴子寄生虫诺氏疟原虫中不存在，包括在孢子体或配子体中特异性上调的基因，这些基因可能与寄生虫在人类之间的成功传播有关。此外，我们提出了15个染色体内部恶性疟原虫特异性基因作为新的候选基因，这些基因可能会增加人类的毒力，并在6号染色体上检测到一个目前尚未确定的间日疟原虫特异性基因簇，可能参与红细胞侵袭。总之，疟原虫物种以蛋白质编码基因的形式存在许多染色体内部差异，其中一些可能与人类疾病有关，因此有希望为未来的实验室研究提供线索。疟疾每年感染2.5亿多人，死亡100多万人，仍然是全世界最具破坏性的传染病之一。随着人类和非人类疟原虫（疟疾的病原体）的完整基因组序列的可用性，现在有可能使用比较基因组学作为一种工具来寻找存在于某些但不是所有疟原虫物种中的基因。这些物种亚群特异性基因可能是疟疾寄生虫之间重要表型差异的基础，并可能为开发预防和治疗人类疟疾的新策略提供重要线索。在这项研究中，我们对六种疟原虫的基因组进行了全面的计算比较，其中包括两种人类疟原虫（恶性疟原虫和间日疟原虫）、一种猴子疟原虫（诺氏疟原虫）和三种啮齿动物疟原虫（伯氏疟原虫、约氏疟原虫和沙巴蒂疟原虫）。这一比较揭示了许多物种亚群特异性基因可能与人类致病性、人际传播性和人类毒力有关。这些基因现在可以通过有针对性的实验分析来进一步检查，以测试预测的表型关联并阐明基因功能。
Genes underlying important phenotypic differences between Plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. We hypothesized that chromosome-internal regions of Plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. We combined sequence similarity searches with synteny block analyses to identify species subset-specific genes in chromosome-internal regions of six published Plasmodium genomes, including Plasmodium falciparum, Plasmodium vivax, Plasmodium knowlesi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium chabaudi. To improve comparative analysis, we first revised incorrectly annotated gene models using homology-based gene finders and examined putative subset-specific genes within syntenic contexts. Confirmed subset-specific genes were then analyzed for their role in biological pathways and examined for molecular functions using publicly available databases. We identified 16 genes that are well conserved in the three primate parasites but not found in rodent parasites, including three key enzymes of the thiamine (vitamin B1) biosynthesis pathway. Thirteen genes were found to be present in both human parasites but absent in the monkey parasite P. knowlesi, including genes specifically upregulated in sporozoites or gametocytes that could be linked to parasite transmission success between humans. Furthermore, we propose 15 chromosome-internal P. falciparum-specific genes as new candidate genes underlying increased human virulence and detected a currently uncharacterized cluster of P. vivax-specific genes on chromosome 6 likely involved in erythrocyte invasion. In conclusion, Plasmodium species harbour many chromosome-internal differences in the form of protein-coding genes, some of which are potentially linked to human disease and thus promising leads for future laboratory research. With more than 250 million infections and over a million deaths each year, malaria remains one of the most devastating infectious diseases worldwide. With the availability of complete genome sequences of both human and non-human Plasmodium parasites, the causative agents of malaria, it is now possible to use comparative genomics as a tool to look for genes that are present in some but not all Plasmodium species. Such species subset-specific genes possibly underlie important phenotypic differences between malaria parasites and could provide important clues for the development of new strategies to prevent and treat malaria in humans. In this study, we performed a comprehensive computational comparison of the published genomes of six Plasmodium species, including two human (P. falciparum and P. vivax), one monkey (P. knowlesi), and three rodent malaria parasites (P. berghei, P. yoelii, and P. chabaudi). This comparison revealed many species subset-specific genes that are potentially linked to human pathogenicity, human-to-human transmissibility, and human virulence. These genes can now be examined further by targeted experimental analyses to test predicted phenotypic associations and to elucidate gene function.
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影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
3
作者：
Bréhélin L;Dufayard JF;Gascuel O
通讯作者：
Gascuel O
影响因子：
15.8
作者：
Alonso PL;Brown G;Arevalo-Herrera M;Binka F;Chitnis C;Collins F;Doumbo OK;Greenwood B;Hall BF;Levine MM;Mendis K;Newman RD;Plowe CV;Rodríguez MH;Sinden R;Slutsker L;Tanner M
通讯作者：
Tanner M
DOI：
10.1073/pnas.0807404105
发表时间：
2008-10-21
影响因子：
11.1
作者：
Bozdech, Zbynek;Mok, Sachel;Preiser, Peter R.
通讯作者：
Preiser, Peter R.
影响因子：
10.7
作者：
DeBarry JD;Kissinger JC
通讯作者：
Kissinger JC