Evolutionary Systems Biology of Host-Parasite Interactions

摘要 我们对全基因组功能基因如何发挥作用的理解存在着根本的差距 宿主-寄生虫相互作用的变异是由自然选择决定的，包括对人类来说。 寄生蠕虫(包括线虫)是影响寄主性状和 潜在的遗传变异。感染压力的地理倾斜，因为蠕虫是体温过高的 (温度敏感)，可能会导致寄主种群的基因组和表型变异。 这反过来可能会影响寄生虫的适应。然而，机械连接剂 寄主和寄生虫的目标性状及其潜在遗传结构的选择 仍然具有巨大的挑战性。只有解决了这一问题，我们才能理解选择是如何驱动的 寄主抗性的进化和免疫系统对寄生虫的抑制和逃避。这个 研究人员的长期目标是获得机械性的理解，包括对基因 关键寄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，研究它们的遗传基础，并从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，迫使其中一方 另一种是通过遗传和表型变化来适应。其基本原理是 植物和它们的线虫寄生虫，作为遗传上易处理的模式系统，表现出空间和 感染率的时间变化，这是有遗传基础的，允许全面 对这个问题的机械论研究。研究人员先前的研究和稳健的工作 初步数据，这一假说将通过：1)确定全基因组的变化 植物对线虫寄生抗性的潜在地理变异，以及2)决定 线虫突破寄主抗性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异 潜在的适应性特征。这将与寄生虫复活生态和 用于研究实时进化变化的实验进化。调查员展示了 以前，这种方法将成功地识别物种中涉及的关键特征和基因 互动。分子遗传学实验将把候选的适应性遗传变异与 功能特征和适合性。这一创新研究计划将形成关键的一步， 对寄主-寄生虫相互作用如何通过选择来塑造的综合理解 表型和全基因组遗传变异。它为揭示一般原则带来了希望 与宿主-寄生虫相互作用如何演变有关，有助于预测人类的可持续性 干预措施塑造这种互动，为人类带来更好的结果。

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.