Evolution of Plasmodium vivax and Asian Macaque Malarias

间日疟原虫和亚洲猕猴疟疾的进化

• 批准号: 8134224
• 负责人: Ananias Alberto Escalante
• 金额: $ 29.88万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8134224
• 关键词: Africa; Africa South of the Sahara; Area; Asia; Asians; Binding; Central America; Cercopithecidae; Complex; Data; Developing Countries; Development; Erythrocytes; Event; Evolution; Frequencies; Genes; Genetic Polymorphism; Genetic Variation; Health; Homo; Human; Intervention; Investigation; Life Cycle Stages; Link; Macaca; Maintenance; Malaria; Malaria Vaccines; Measures; Methods; Molecular; Morbidity - disease rate; Mutation; Natural Selections; Nuclear; Parasites; Pattern; Pharmaceutical Preparations; Phylogenetic Analysis; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Population; Population Genetics; Population Growth; Poverty; Process; Proteins; Public Health; Radiation; Recording of previous events; Reporting; Role; Sampling; Sister; South America; Southeastern Asia; Specificity; Structure; System; Taxon; Testing; Vaccines; Variant; comparative; disorder risk; improved; mitochondrial genome; mortality; nonhuman primate; novel strategies; simulation; southeast Asian; transmission process

DESCRIPTION (provided by applicant): PLASMODIUM VIVAX is the most prevalent human malarial parasite in several areas of Asia and South-Central America. Phylogenetic studies have shown that P. vivax and other Plasmodium spp. currently found in Southeast Asian macaques are part of a monophyletic group from which P. vivax originated as a human parasite as a result of a host switch. The proposed investigation seeks to understand the evolutionary history of P. vivax together with its known sister taxa in Southeast Asian macaques. Understanding the evolutionary history of macaque malarias is important because some of these parasites can infect humans. Overall, the proposed investigation aims to understand the role of positive selection in the evolution of proteins expressed during erythrocyte invasion in P. vivax and related species. This is a critical step in the parasite life cycle. Several of these proteins are considered targets for malaria vaccines. Spurious evidence of positive selection, however, could result from demographic processes (such as population growth and population structure). Thus we propose to assess the demographic histories of P. vivax and macaque Plasmodium spp., using extensive geographic sampling to understand the evolution of putative adaptive variation. This proposal includes two interrelated aims: Specific aim 1: To investigate the demographic histories of P. vivax and related macaque malarial parasite populations. This investigation will allow us to test the following hypotheses: a) P. vivax originated in Asia as a H. sapiens parasite and has a complex demographic history that includes population expansions outside Asia; b) although host switches have been reported in Plasmodium spp., we hypothesize that within-host-species transmission has been be favored over between-host-species transmission. Thus, we expect to find host-specific lineages in multi-host Plasmodium associated with Southeast Asian macaques. Such lineages will provide a suitable framework to estimate the mutation rates at neutral loci, and by so doing, we can improve our understanding of the recent demographic history of P. vivax. Specific aim 2: To investigate the mode of evolution, extent, and maintenance of genetic diversity in erythrocyte invasion proteins (EIP) in P. vivax and related species. We hypothesize that among the EIP, divergence due to natural selection in the P. vivax branch will be observed in proteins which reflect molecular adaptations of this parasite to Homo after it switched from Cercopithecidae hosts. Second, we will sequence loci encoding EIP proteins in extant populations of P. vivax and related macaque malarial parasites. We will explore their observed polymorphism by using comparative and coalescent simulations approaches. We will test the hypothesis that putative adaptive polymorphisms will be observed in P. vivax EIP, especially at those proteins known to bind the erythrocyte. PUBLIC HEALTH RELEVANCE Although P. vivax is the most prevalent malarial parasite outside Sub-Saharan Africa, there is little information about its genetic diversity. Such information is essential for developing and deploying control measures such as vaccines and drugs. This investigation will also provide information about the distribution, frequency, and host-specificity of macaque malarias. Since these parasites have been found to infect humans in Southeast Asia, understanding their distribution and genetic diversity will be an important first step in assessing the disease risk for humans.

描述（由申请人提供）：间日疟原虫是亚洲和中南美洲多个地区最流行的人类疟疾寄生虫。系统发育研究表明，间日疟原虫和其他疟原虫属。目前在东南亚猕猴中发现的猕猴属于单系群的一部分，间日疟原虫由于宿主转换而起源于人类寄生虫。拟议的调查旨在了解间日疟原虫及其已知的东南亚猕猴姐妹类群的进化历史。了解猕猴疟疾的进化史很重要，因为其中一些寄生虫可以感染人类。总体而言，拟议的研究旨在了解正选择在间日疟原虫及相关物种红细胞侵袭过程中表达的蛋白质进化中的作用。这是寄生虫生命周期中的关键步骤。其中一些蛋白质被认为是疟疾疫苗的靶标。然而，人口统计过程（例如人口增长和人口结构）可能会产生积极选择的虚假证据。因此，我们建议评估间日疟原虫和猕猴疟原虫属的人口历史，使用广泛的地理采样来了解假定的适应性变异的进化。该提案包括两个相互关联的目标： 具体目标 1：调查间日疟原虫和相关猕猴疟疾寄生虫种群的人口历史。这项调查将使我们能够检验以下假设： a) 间日疟原虫作为智人寄生虫起源于亚洲，并具有复杂的人口历史，包括亚洲以外的人口扩张； b）尽管在疟原虫属中已经报道了宿主转换，但我们假设宿主种内传播比宿主种间传播更受青睐。因此，我们期望在与东南亚猕猴相关的多宿主疟原虫中找到宿主特异性谱系。这样的谱系将提供一个合适的框架来估计中性位点的突变率，通过这样做，我们可以增进对间日疟原虫近期人口统计历史的了解。具体目标2：研究间日疟原虫及相关物种红细胞侵袭蛋白（EIP）遗传多样性的进化模式、范围和维持。我们假设，在 EIP 中，由于间日疟原虫分支中的自然选择而导致的分歧将在蛋白质中观察到，这反映了这种寄生虫从鹿科宿主转变为人属后的分子适应。其次，我们将对现有间日疟原虫和相关猕猴疟疾寄生虫种群中编码 EIP 蛋白的基因座进行测序。我们将通过使用比较和合并模拟方法来探索他们观察到的多态性。我们将测试以下假设：在间日疟原虫 EIP 中观察到推定的适应性多态性，尤其是那些已知与红细胞结合的蛋白质。公共卫生相关性 尽管间日疟原虫是撒哈拉以南非洲地区以外最流行的疟疾寄生虫，但有关其遗传多样性的信息却很少。此类信息对于开发和部署疫苗和药物等控制措施至关重要。这项调查还将提供有关猕猴疟疾的分布、频率和宿主特异性的信息。由于这些寄生虫被发现感染东南亚的人类，了解它们的分布和遗传多样性将是评估人类疾病风险的重要第一步。

项目成果

Evaluation of the genetic diversity of domain II of Plasmodium vivax Apical Membrane Antigen 1 (PvAMA-1) and the ensuing strain-specific immune responses in patients from Sri Lanka.

评估斯里兰卡患者间日疟原虫顶膜抗原 1 (PvAMA-1) 结构域 II 的遗传多样性以及随后的菌株特异性免疫反应。

• DOI: 10.1016/j.vaccine.2011.07.029
• 发表时间: 2011-10-06
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: S. Dias;M. Somarathna;A. Manamperi;A. Escalante;A. Gunasekera;P. Udagama
• 通讯作者: P. Udagama

The genetic diversity of Plasmodium vivax populations.

间日疟原虫种群的遗传多样性。

• DOI: 10.1016/s1471-4922(03)00085-0
• 发表时间: 2003-05-01
• 期刊: Trends in parasitology
• 影响因子: 9.6
• 作者: L. Cui;A. Escalante;M. Imwong;G. Snounou
• 通讯作者: G. Snounou

Description and molecular characterization of Haemoproteus macrovacuolatus n. sp. (Haemosporida, Haemoproteidae), a morphologically unique blood parasite of black-bellied whistling duck (Dendrocygna autumnalis) from South America.

Haemoproteus macrovacuolatus n. 的描述和分子特征。

• 发表时间: 2014-08
• 影响因子: 2
• 作者: Matta, Nubia E;Pacheco, M Andreína;Escalante, Ananias A;Valkiūnas, Gediminas;Ayerbe;Acevedo
• 通讯作者: Acevedo

Malarial parasite diversity in chimpanzees: the value of comparative approaches to ascertain the evolution of Plasmodium falciparum antigens.

黑猩猩中的疟疾寄生虫多样性：比较方法确定恶性疟原虫抗原进化的价值。

• 发表时间: 2013-09-17
• 影响因子: 3
• 作者: Pacheco, M Andreína;Cranfield, Michael;Cameron, Kenneth;Escalante, Ananias A
• 通讯作者: Escalante, Ananias A

Description of Leucocytozoon quynzae sp. nov. (Haemosporida, Leucocytozoidae) from hummingbirds, with remarks on distribution and possible vectors of leucocytozoids in South America.

白细胞虫 quynzae sp 的描述。

• 发表时间: 2014-02
• 影响因子: 2
• 作者: Matta, Nubia E;Lotta, Ingrid A;Valkiūnas, Gediminas;González, Angie D;Pacheco, M Andreína;Escalante, Ananias A;Moncada, Ligia I;Rodríguez
• 通讯作者: Rodríguez