2019-EEID US-UK Heterogeneities, Diversity and the Evolution of Infectious Disease

传染病在人群中的传播很少近似于同质的、随机的“充分混合”过程。个体宿主通过遗传和表观遗传效应、自身状况和免疫记忆，其易感性和传播性各不相同。此外，由于个体在空间中的排列方式、他们如何移动以及即使在环境中没有异质性的情况下，他们如何在社会上相互作用而产生种群结构，疾病接触的变化在种群内是典型的。在大多数（如果不是全部）系统中，这些个体异质性和种群结构引起的传播异质性与宿主基因型和寄生虫菌株之间特异性的差异相互作用。对于这三种异质性来源——个体、群体和相互作用——对疾病流行病学的影响，我们的理论并不完整。例如，“超级传播者”在SARS中的作用是一个典型的例子，说明疾病接触的异质性对流行病结果的重要性。此外，我们对这种异质性对传染病演变的影响的理解相对较少，超出了理论和有限的关于规则空间结构作用的实验测试。特别是，不同的异质性如何相互作用，以确定疾病毒力和宿主防御的进化很少被研究。因此，需要新的理论来检验它们对长期进化结果的影响，但也许更重要的是，我们需要了解短暂的短期反应。本研究将解决的主要智力挑战是：(1)扩展现有理论，以理解种群和个体水平异质性及其相互作用对宿主和寄生虫性状进化的影响；(2)发展新的理论方法来预测瞬时进化行为；(3)在可处理的实验室模型系统中验证这些预测；(4)将该理论应用于农业系统，以了解农业进化反馈和管理强加的异质性对进化传染病的作用。

Infectious disease transmission within populations rarely approximates as a homogenous, random "well mixed" process. Individual hosts vary in their susceptibility and transmissibility through genetic and epigenetic effects, their condition and their immune memory. In addition, variation in disease contacts is typical within populations due to how individuals are arranged in space, how they move and how they interact socially generating population structure even in the absence of heterogeneities in the environment. These individual heterogeneities and the heterogeneity in transmission due to population structure interact with variation in specificity between host genotypes and parasites strains in most if not all systems. We have an incomplete theory on what each of these three sources of heterogeneities - individual, population and interaction - have on the epidemiology of disease. For example, the role of 'superspreaders' in the SARS is a classic example of the importance of heterogeneity in disease contacts to epidemic outcomes. Furthermore, we have relatively little understanding of the implications of such heterogeneity to the evolution of infectious disease beyond theory and limited experimental tests on the role of regular spatial structure. In particular, how different heterogeneities interact to determine the evolution of disease virulence and host defense is little studied. New theory is therefore required to test their implications to the long-term evolutionary outcomes, but perhaps more importantly we need to understand transient short-term responses. The key intellectual challenges that this proposal will address are to (1) extend existing theory to understand the impact of population and individual level heterogeneities and their interaction on the evolution of host and parasite traits, (2) develop new theoretical methods to predict the transient evolutionary behavior, (3) test these predictions in a tractable laboratory model system and (4) apply the theory to agricultural systems to understand the role of agri-evolutionary feedbacks and management imposed heterogeneities on the evolution infectious disease.