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; 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.

抽象的 我们对全基因组功能遗传的理解有根本的差距 宿主 - 寄生虫相互作用的变化是由自然选择（包括人类）所塑造的。 寄生虫（包括线虫）呈现宿主特征的重要选择剂， 潜在的遗传变异。在感染压力下的地理座椅，因为蠕虫是热热的 （温度敏感）可能会驱动宿主种群之间的基因组和表型变异。 反过来，这可能会影响寄生虫的适应性。但是，机械师将代理联系 在宿主和寄生虫中使用目标性状及其潜在的遗传结构进行选择 仍然是正式的挑战。只有在解决时，我们才能了解选择如何驱动 寄主的抗药性和免疫系统抑制和寄生虫进化的演变。 研究者的长期目标是获得机械理解，包括通用 关键宿主和寄生虫特征的建筑。实验室的五年目标是确定这些 关键特征，研究其遗传基础，并在功能上验证调节它们的遗传变异。 核心假设是共同发展的宿主和寄生虫施加选择，施加了一个压力 另一个是通过遗传和表型变化来适应的。理由是 植物及其线虫寄生虫作为一般可拖动的模型系统，显示空间和 感染率的暂时变化，其具有遗传基础，允许全面 此问题的机械研究。努力研究调查员的先前研究和强大的研究 初步数据，该假设将通过：1）识别全基因组变化 植物对线虫寄生虫的抵抗力的潜在地理差异，以及2）确定 遗传机制和约束在线虫中破坏宿主的抗性。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异 潜在的适应性特征。这将与寄生虫复活生态学和 研究实时进化变化的实验进化。调查员表明 以前，这种方法将成功识别物种涉及的关键特征和基因 互动。分子遗传实验将将候选自适应遗传变异与 功能性状和健身。该创新的研究计划将构成迈向的关键一步 综合理解宿主 - 寄生虫相互作用是如何通过选择来塑造的 表型和全基因组遗传变异。它有望揭示一般原则 与宿主寄生虫相互作用的发展有关，有助于预测人类的可持续性 将这种相互作用朝着人类带来更好结果的干预措施。