What makes a super-spreader? The genetic architecture and evolutionary constraints on host heterogeneity in pathogen transmission

是什么造就了超级传播者？

• 批准号: NE/X009904/1
• 负责人: Pedro Vale
• 金额: $ 10.28万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FX009904%2F1
• 关键词: What; makes; super; spreader; genetic

Super-spreaders of infectious diseases are the most spectacular examples of host heterogeneity in pathogen transmission. What makes a superspreader? Despite their importance in driving the spread of infections in natural populations, we have a poor understanding of how host genetics contributes to variation in host traits that drive pathogen spread, and almost no understanding of the genetic basis of superspreading. We will address two key questions: 1. How much of host variation in pathogen transmission is explained by their genetics? 2. What are the evolutionary constraints on extreme pathogen shedding phenotypes? Using a naturally-derived population of fruit flies, we will quantify the phenotypic variation in locomotor activity, pathogen shedding, and host susceptibility following infection with the bacterial pathogen Pseudomonas aeruginosa. We will then quantify how much of the phenotypic variance in these traits is explained by among-line genetic variance. In a second experiment, we will experimentally evolve super-shedders. We will start from a genetically variable outbred population and artificially select for extreme pathogen shedding phenotypes and then measure the direct and correlated responses to selection to identify evolutionary constraints on super-shedding individuals.

传染病的超级传播者是病原体传播中宿主异质性的最引人注目的例子。是什么造就了超级传播者？尽管它们在推动自然种群中感染传播方面具有重要意义，但我们对宿主遗传学如何促进宿主性状变异的理解很差，这些变异驱动病原体传播，并且几乎不了解超级传播的遗传基础。我们将解决两个关键问题：1。病原体传播中宿主的变异有多少是由它们的遗传学解释的？2.极端病原体脱落表型的进化限制是什么？使用自然来源的果蝇种群，我们将量化与细菌病原体铜绿假单胞菌感染后的自发活动，病原体脱落和宿主易感性的表型变化。然后，我们将量化这些性状中有多少表型方差是由同系遗传方差解释的。在第二个实验中，我们将实验性地进化出超级脱落者。我们将从一个遗传可变的远交种群开始，人工选择极端病原体脱落表型，然后测量对选择的直接和相关反应，以确定对超级脱落个体的进化约束。