RAPID: Investigation of Natural Selection and Host-microbiome-virome Interactions in an Unprecedented and Ongoing Marine Epidemic

大型传染病的爆发使得宿主、感染性病原体和宿主内的微生物群落（微生物组）的进化变化相对较快。虽然人们对这些相互作用知之甚少，但它们在预测和控制未来疫情方面极其重要。有记录以来最大的海洋流行病目前正在北美西海岸的潮间带生态系统中发生。海星消瘦病（sssd）正在影响从阿拉斯加东南部到墨西哥下加利福尼亚州的海星种群，当地的灭绝是一个严重的问题。随着全球环境和物种种群分布的变化，预计此类大规模流行病将变得更加普遍。当前的这一疾病事件提供了一个独特的机会，可以更好地了解宿主、宿主微生物组和引起疾病的病原体在整个流行病期间如何变化。本文提出的研究将从进化和生态学的角度对这些疾病事件进行更深入的理解，通过描述流行病后自然选择导致的宿主和病原体的变化。本项目旨在了解微生物组和病毒组在个体、群体和社区水平上对宿主疾病状态和进展的影响。这项工作将有助于理解有机体作为其居民的总和，并将剖析微生物群落在对疾病的生理和进化反应中的作用。疾病往往是由于生物体复杂的微生物群落的平衡受到破坏。因此，疾病的进化不是两个参与者（宿主和病原体）的共同进化，而是宿主群落所有成员的共同进化。正在进行的海星消耗病事件提供了一个独特的机会来调查这种进化如何在广泛的流行病中发挥作用。具体而言，该研究旨在(1)确定宿主和病毒种群中自然选择的目标；(2)研究宿主、病毒和微生物组中强调宿主耐药性和病毒毒力的分子机制，以确定无症状宿主和有症状宿主之间的临界点。这将使用一种新的测序技术来完成，该技术同时收集真核宿主、细菌群落和病毒群落的转录本的序列数据。这种方法允许识别交互中的主要参与者以及他们的功能角色。对这种复杂的共同进化的理解将影响疾病生态学和进化领域，以及影响野生动物和人类疾病的理解方式，并有希望预防或控制。

Large infectious disease outbreaks allow for relatively faster evolutionary changes in the host, the infectious pathogen, and the community of microorganisms living within the host (the microbiome). While these interactions are poorly understood, they're extremely important in predicting and controlling future outbreaks. The largest recorded marine epidemic ever recorded is currently ongoing in intertidal ecosystems along the west coast of North America. Sea star wasting disease (SSWD) is effecting sea star populations from South Eastern Alaska to Baja California, Mexico and local extinctions are a serious concern. Large-scale epidemics such as these are expected to become more common as the global environment and species' population distributions change. This current disease event provides a unique opportunity to better understand how hosts, the hosts' microbiome, and the disease causing pathogen change throughout an epidemic. The research proposed here will lead to a deeper understanding of these disease events from an evolutionary and ecological perspective by characterizing changes in host and pathogen due to natural selection following epidemics.This project aims to understand the impact of the microbiome and virome on host disease status and progression at the individual, population, and community levels. The work will contribute to the understanding of an organism as a sum of its inhabitants and will dissect the role of the microbial community in physiological and evolutionary responses to disease. Disease may often be due to a disruption in the balance of an organisms' complex community of microorganisms. Thus, the evolution of disease is not the coevolution of two players (host and pathogen), but rather the coevolution of all members of the host's community. The ongoing Sea Star Wasting Disease event provides a unique opportunity to investigate how this evolution plays out in a widespread epidemic. Specifically, the proposed research aims to (1) identify the targets of natural selection in host and virus populations and (2) investigate molecular mechanisms in the host, virus, and microbiome that underline resistance in hosts and virulence in virus in order to identify the tipping point between asymptomatic and symptomatic hosts. This will be accomplished using a novel sequencing technique that simultaneously collects sequence data from the transcripts of the eukaryotic host, bacterial community, and viral community. This approach allows for identification of the major players in the interaction as well as their functional roles. The understanding of this complicated coevolution will impact the fields of disease ecology and evolution as well as affect the way wildlife and human diseases are understood and, hopefully, prevented or controlled.