In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.
In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.
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对疟疾寄生虫基因组的深入比较分析揭示了恶性疟原虫基因组中与人类疾病相关的蛋白质编码基因。
DOI：
10.1186/s12864-018-4654-5
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发表时间：
2018-05-02
期刊：
影响因子：
4.4
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Liu X;Wang Y;Liang J;Wang L;Qin N;Zhao Y;Zhao G
恶性疟原虫是毒性最强的疟原虫，能够寄生在人类红细胞上。与这种能力相关的基因的鉴定可以增强我们对人类疟疾分子机制的理解，并导致开发新的疟疾控制治疗策略。随着几种疟原虫基因组序列的出现，进行计算分析现在是识别导致这种疾病的基因的实用策略。在这里，我们开发并使用虚拟基因组方法将来自三种人类疟疾寄生虫（即恶性疟原虫、诺氏疟原虫和间日疟原虫）以及三种啮齿类疟疾寄生虫（即伯氏疟原虫、恰鲍迪疟原虫和约氏疟原虫）的 33,314 个基因分配到 4605 个簇中。每个簇由蛋白质序列显着相似的基因组成，被认为是虚拟基因。将人类疟疾寄生虫中所有簇的富集值与啮齿动物疟疾寄生虫中的所有簇的富集值进行比较，发现 115 个恶性疟原虫基因可能负责寄生人类红细胞。这些基因主要位于染色体内部区域，参与许多生物过程，包括膜蛋白运输和硫胺素生物合成。同时，289 个伯氏疟原虫基因包含在啮齿动物寄生虫富集的簇中。大多数位于亚端粒区域并编码红细胞表面蛋白。将恶性疟原虫与间日疟原虫和诺氏疟原虫的簇值进行比较，发现有 493 个与毒力相关的候选基因。其中一些编码存在于红细胞表面的蛋白质，并参与细胞粘附、毒力因子运输或红细胞侵袭，但也鉴定出了许多功能未知的基因。脑型疟疾的特征是受感染的红细胞在滋养体阶段在脑微血管中积聚。为了发现脑型疟疾相关基因，引入快速傅里叶变换（FFT）来提取在滋养体阶段高度转录的基因。最终鉴定出55个候选基因。考虑到寄生虫感染的红细胞表面蛋白2（PIESP2）含有间隙连接相关的Neuromodulin_N结构域，并且抗PIESP2可能提供针对疟疾的保护作用，我们选择PIESP2进行进一步的实验研究。我们的分析揭示了恶性疟原虫基因组中与人类疾病相关的有限数量的基因。这些基因可能是进一步功能表征的有趣目标。本文的在线版本 (10.1186/s12864-018-4654-5) 包含补充材料，可供授权用户使用。
Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease. Here, we developed and used a virtual genome method to assign 33,314 genes from three human malaria parasites, namely, P. falciparum, P. knowlesi and P. vivax, and three rodent malaria parasites, namely, P. berghei, P. chabaudi and P. yoelii, to 4605 clusters. Each cluster consisted of genes whose protein sequences were significantly similar and was considered as a virtual gene. Comparing the enriched values of all clusters in human malaria parasites with those in rodent malaria parasites revealed 115 P. falciparum genes putatively responsible for parasitizing human erythrocytes. These genes are mainly located in the chromosome internal regions and participate in many biological processes, including membrane protein trafficking and thiamine biosynthesis. Meanwhile, 289 P. berghei genes were included in the rodent parasite-enriched clusters. Most are located in subtelomeric regions and encode erythrocyte surface proteins. Comparing cluster values in P. falciparum with those in P. vivax and P. knowlesi revealed 493 candidate genes linked to virulence. Some of them encode proteins present on the erythrocyte surface and participate in cytoadhesion, virulence factor trafficking, or erythrocyte invasion, but many genes with unknown function were also identified. Cerebral malaria is characterized by accumulation of infected erythrocytes at trophozoite stage in brain microvascular. To discover cerebral malaria-related genes, fast Fourier transformation (FFT) was introduced to extract genes highly transcribed at the trophozoite stage. Finally, 55 candidate genes were identified. Considering that parasite-infected erythrocyte surface protein 2 (PIESP2) contains gap-junction-related Neuromodulin_N domain and that anti-PIESP2 might provide protection against malaria, we chose PIESP2 for further experimental study. Our analysis revealed a limited number of genes linked to human disease in P. falciparum genome. These genes could be interesting targets for further functional characterization. The online version of this article (10.1186/s12864-018-4654-5) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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