Influence of local adaptation and demographic constraints on patterns of wildlife disease spread

气候变化正在改变许多物种的疾病动态。然而，目前尚不清楚物种适应这些变化的能力，也不清楚自然遗传变异模式对疾病传播的影响。在此，我建议研究宿主免疫基因变异、疾病变异和中性群体遗传参数之间的相互作用，以增强我们对物种如何应对快速变化的疾病动态、这些过程的限制以及疾病传播模式的理解。北极狂犬病（AR）提供了一个模型系统来了解北方物种对疾病模式快速变化的反应能力，其中气候变化对AR的动态有显著影响。AR系统包括具有不同疾病易感性和时间疾病暴露模式的多个宿主，这使得测试关于AR与其宿主遗传相互作用的假设成为可能。此外，该系统在疾病的局部化和跨极地分布的传播方面呈现出对比。具体来说，我们将评估：1)利用序列捕获和下一代测序技术从宿主的适应性免疫基因和先天免疫基因中获得的免疫遗传变异，2)感染宿主的AR菌株的全基因组分析，3)和中性基因，以深入了解种群内部和种群之间的当代和历史人口统计学过程以及人口统计学对当地适应的限制。这项研究是一项创新，它采用了多管齐下的方法，将宿主和病原体的自然遗传变异研究结合起来，以了解野生动物疾病的传播，这种方法可以扩展到其他疾病系统。鉴于野生动物疾病对北部人口的人类健康的影响以及对野生动物健康和持久性的影响，这些问题对加拿大具有实际意义。

Climatic changes are altering disease dynamics for many species. It is unclear, however, what capacity species have to adapt to these changes, nor the influence patterns of natural genetic variation have on disease spread. Herein, I propose to study interactions between host immune gene variation, disease variants, and neutral population genetic parameters to enhance our understanding of how species respond to rapidly changing disease dynamics, constraints on these processes, and patterns of disease spread. Arctic rabies (AR) provides a model system to understand the capacity for northern species to respond to rapid changes in disease patterns where climatic changes are having a pronounced effect on the dynamics of AR. The AR system includes multiple hosts with contrasting patterns of disease susceptibility and temporal disease exposure, making it possible to test hypotheses regarding the genetic interactions of AR with its hosts. Further, this system presents contrasts in the localization and spread of disease across its circumpolar distribution. Specifically, we will assess: 1) immunogenetic variation derived from adaptive immunity genes and innate immunity genes of hosts using sequence capture and next generation sequencing technologies, 2) whole genome profiling of AR strains from infected hosts, 3) and neutral genes to provide insight into contemporary and historical demographic processes within and among the populations and demographic constraints on local adaptation. This research is innovative by taking the multi-pronged approach of integrating studies of natural genetic variation in hosts and pathogens towards understanding wildlife disease spread, an approach that can be extended to other disease systems. These questions are of practical relevance to Canada given human health impacts from wildlife disease on northern populations and effects on wildlife health and persistence.