Evolutionary Systems Biology of Host-Parasite Interactions

宿主-寄生虫相互作用的进化系统生物学

• 批准号: 10716048
• 负责人: Simon Cornelis Groen
• 金额: $ 37.93万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10716048
• 关键词: Address; Animals; Area; Autoimmune; Biological Models; Comprehension; Data; Ecology; Evolution; Experimental Genetics; Genes; Genetic; Genetic Variation; Genomics; Geography; Goals; Growth and Development function; Helminths; Host resistance; Human; Immune system; Infection; Intervention; Knowledge; Laboratories; Link; Mission; Molecular Genetics; Mutation; National Institute of General Medical Sciences; Natural Selections; Nematoda; Organism; Outcome; Parasites; Pathology; Phenotype; Plants; Population; Population Genetics; Process; Public Health; Research; Research Personnel; Resistance; Shapes; System; Systems Biology; Temperature; Testing; Time; United States National Institutes of Health; Variant; fitness; genetic approach; genetic architecture; genetic variant; genome-wide; genome-wide analysis; geographic difference; infection rate; innovation; parasitism; pressure; programs; trait

ABSTRACT There are fundamental gaps in our understanding of how genome-wide functional genetic variation in host-parasite interactions is shaped by natural selection, including for humans. Parasitic helminths (including nematodes) present important selective agents on host traits and underlying genetic variation. Geographic clines in infection pressure, as helminths are ectothermic (temperature-sensitive), may drive genomic and phenotypic variation across host populations. This, in turn, may influence parasite adaptation. However, mechanistically linking agents of selection with targeted traits and their underlying genetic architecture in hosts and parasites remains formidably challenging. Only when resolved, will we understand how selection drives evolution of host resistance and immune system suppression and evasion by parasites. The investigator’s long-term goal is to gain mechanistic understanding, including of the genetic architecture of key host and parasite traits. The laboratory’s five-year objective is to identify these key traits, investigate their genetic basis, and functionally verify genetic variants regulating them. The core hypothesis is that coevolving hosts and parasites exert selection, pressuring one another to adapt through genetic and phenotypic changes. The rationale is that populations of plants and their nematode parasites, as genetically tractable model systems, show spatial and temporal variation in infection rates, which has a genetic basis, allowing comprehensive mechanistic studies of this issue. Working off the investigator’s prior research and robust preliminary data, this hypothesis will be tested through: 1) identifying genome-wide changes underlying geographic variation in plant resistance to nematode parasitism, and 2) determining genetic mechanisms and constraints underlying host resistance-breaking in nematodes. An evolutionary systems biology approach will identify genes, genetic networks and genomic variants underlying adaptive traits. This will be combined with parasite resurrection ecology and experimental evolution to study real-time evolutionary change. The investigator showed previously that such approaches will successfully identify key traits and genes involved in species interactions. Molecular genetic experiments will link candidate adaptive genetic variants with functional traits and fitness. This innovative research program will form a key step toward integrative comprehension of how host-parasite interactions are shaped by selection on phenotypic and genome-wide genetic variation. It holds promise for uncovering general principles relating to how host-parasite interactions evolve, helping predict sustainability of human interventions in shaping such interactions towards better outcomes for humans.

摘要 在我们对全基因组功能性遗传学是如何运作的理解上， 宿主-寄生虫相互作用的变化是由自然选择决定的，包括对人类而言。 寄生蠕虫（包括线虫）对宿主性状具有重要的选择作用， 潜在的遗传变异感染压力的地理倾斜，因为蠕虫是变温的 （温度敏感），可以驱动宿主群体之间的基因组和表型变异。 这反过来又可能影响寄生虫的适应。然而，本发明的机械连接剂 宿主和寄生虫中目标性状及其潜在遗传结构的选择 仍然是个巨大的挑战只有解决了这个问题，我们才能理解选择是如何驱动 宿主抗性的进化以及寄生虫对免疫系统的抑制和逃避。的 研究者的长期目标是获得机械的理解，包括遗传学的理解。 关键宿主和寄生虫特征的结构。该实验室的五年目标是确定这些 关键性状，研究其遗传基础，并在功能上验证调节它们的遗传变异。 核心假设是共同进化的宿主和寄生虫施加选择， 另一种是通过遗传和表型变化来适应。理由是， 植物和它们的线虫寄生虫，作为遗传上易处理的模型系统，显示出空间和 感染率的时间变化具有遗传基础， 对这个问题的机械研究。利用调查员先前的研究成果 根据初步数据，这一假设将通过以下方式进行检验：1）识别全基因组变化 植物对线虫寄生抗性的潜在地理变异，以及2）确定 线虫宿主抗性破坏的遗传机制和制约因素。一个 进化系统生物学方法将识别基因、遗传网络和基因组变体 潜在的适应性特征这将与寄生虫复活生态学相结合， 实验进化来研究实时进化变化。调查显示， 以前，这种方法将成功地确定物种的关键特征和基因， 交互.分子遗传学实验将把候选适应性遗传变异与 功能性状和适应性。这一创新的研究计划将形成一个关键步骤， 综合理解宿主-寄生虫相互作用是如何通过选择形成的， 表型和全基因组遗传变异。它有希望揭示一般原则 与宿主-寄生虫相互作用如何演变有关，有助于预测人类 干预措施，以塑造这种互动，为人类带来更好的结果。