Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance.
Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance.
复制标题
疟原虫通过改变控制基因组维护的机制进化宿主特异性。
DOI：
10.1128/mbio.03272-19
复制
发表时间：
2020
期刊：
影响因子：
6.4
通讯作者：
Kirkman,LauraA
中科院分区：
文献类型：
--
作者：
Siao,MichelleC;Borner,Janus;Perkins,SusanL;Deitsch,KirkW;Kirkman,LauraA
引起疟疾的原生动物寄生虫感染多种脊椎动物宿主，包括鸟类、爬行动物和哺乳动物，宿主与寄生虫关系固有的进化压力深刻地塑造了宿主和寄生虫的基因组。在这里，我们报告说，这些选择压力导致了真核生物学最基本方面之一的意外改变，即通过 DNA 修复维持基因组完整性。感染人类的疟疾寄生虫通过基因家族成员之间频繁的异位重组，在其抗原编码基因家族中不断产生遗传多样性，这一过程是全球疟疾持续存在的一个重要特征。抗原多样性的不断产生确保了不同的寄生虫分离株具有不同的抗原性，从而防止广泛的交叉反应免疫，并使寄生虫能够在人群中保持稳定的传播。然而，基因家族成员之间重组的分子基础尚不清楚。通过对不同疟原虫物种的抗原编码、多拷贝基因家族的计算分析，我们报告了意外的观察结果，即感染啮齿动物的疟原虫没有表现出与恶性疟原虫中观察到的相同程度的抗原多样性，并且似乎经历了显着较少的异位重组。利用比较基因组学，我们还确定了多样化过程的关键分子组成部分，从而为疟疾寄生虫如何平衡基因组完整性的维持与持续遗传多样化的要求提供了新的线索。重要性疟疾仍然是发展中国家最流行和最致命的传染病之一，每年造成约 2.28 亿临床病例和近 50 万人死亡。这种疾病是由疟原虫属原生动物寄生虫引起的，在能够感染人类的五种寄生虫中，恶性疟原虫的感染最为严重。除了感染人类的寄生虫之外，还有数百种其他物种可以感染鸟类、爬行动物和其他哺乳动物，每种物种都经过精心进化，以应对各自宿主生存所固有的特定挑战。通过比较每个物种进化出的独特策略，可以获得对宿主与寄生虫相互作用的关键见解，包括有关人类疾病发病机制的发现。在这里，我们描述了令人惊讶的观察结果，即具有不同宿主的密切相关的寄生虫进化出了截然不同的修复其基因组的方法。这一观察结果对于寄生虫维持慢性感染的能力和宿主免疫力的发展具有重要意义。
The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of differentPlasmodiumspecies, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification.IMPORTANCEMalaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genusPlasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.