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宿主-病原体动态中疾病结局的基因组学研究。

Genomic studies of disease-outcome in host--pathogen dynamics.

作者信息

Longo Ana V, Burrowes Patricia A, Zamudio Kelly R

机构信息

*Department of Ecology and Evolutionary Biology, Cornell University, E145 Corson Hall, Ithaca, NY 14853, USA; Department of Biology, University of Puerto Rico, PO Box 23360, San Juan, PR 00931-3360, USA

*Department of Ecology and Evolutionary Biology, Cornell University, E145 Corson Hall, Ithaca, NY 14853, USA; Department of Biology, University of Puerto Rico, PO Box 23360, San Juan, PR 00931-3360, USA.

出版信息

Integr Comp Biol. 2014 Sep;54(3):427-38. doi: 10.1093/icb/icu073. Epub 2014 Jun 10.

DOI:10.1093/icb/icu073
PMID:24916476
Abstract

Pathogens act as agents of evolutionary change in host populations, altering the host's allele frequencies and phenotypes through selection. The mechanisms underlying these adaptive changes depend on which defense strategy the host adopts upon infection. With increased anthropogenic change and loss of biodiversity, ecological impacts on adaptive processes may reduce the ability of hosts to evolve resistance, or to persist within their tolerance limits, thus increasing the capacity of pathogens to cause disease and mortality. In this review, we use amphibians and a pathogenic chytrid fungus (Batrachochytrium dendrobatidis, Bd) to illustrate how integrating genomic approaches into current research, both for hosts and pathogens, will improve our understanding of factors promoting the outcome of disease. As new emerging pathogens continue threatening amphibian populations worldwide, we recommend that researchers focus on individuals that survive after natural epizootics or experimental challenges. These survivors represent an underutilized and underexploited genetic resource for characterizing adaptive traits involved in the clearance of pathogens or in their tolerance. We highlight two target areas that will benefit from focused research: (1) Identification of the genetic basis of the hosts' defense strategies (resistance and tolerance) and of Bd's pathogenicity traits and (2) genomic characterization of shifts in fitness that drive seasonal and/or temporal patterns in host-pathogen interactions. To provide insights into hosts' survival, we review recent literature--including experimental Bd challenges and longitudinal studies--that underscore the complexity of Bd infections as determined by a combination of genetic and environmental factors. Given the heterogeneity of disease-outcomes and broad diversity of host species, amphibians provide a unique opportunity to identify novel genetic determinants of resistance to a recently emerged fungal pathogen. Developing additional genetic resources (e.g., genomic profiles, resistance mapping, and dual RNA-seq) will advance our understanding of the components of the innate and adaptive immune system acting on infected hosts in varying environments. These ecoimmunomic applications, which link host-pathogen eco-evolutionary processes with applied conservation efforts, will specifically benefit threatened amphibians that remain safeguarded in captive colonies.

摘要

病原体作为宿主种群进化变化的驱动因素,通过选择改变宿主的等位基因频率和表型。这些适应性变化的潜在机制取决于宿主在感染时采取哪种防御策略。随着人为变化的增加和生物多样性的丧失,对适应性过程的生态影响可能会降低宿主进化出抗性的能力,或者降低其在耐受限度内生存的能力,从而增加病原体导致疾病和死亡的可能性。在本综述中,我们以两栖动物和一种致病性壶菌(蛙壶菌,Bd)为例,说明将基因组方法整合到当前针对宿主和病原体的研究中,将如何增进我们对促进疾病结果的因素的理解。由于新出现的病原体持续威胁着全球两栖动物种群,我们建议研究人员关注在自然疫病流行或实验性挑战后存活下来的个体。这些幸存者是一种未得到充分利用和开发的遗传资源,可用于表征参与病原体清除或耐受的适应性性状。我们强调两个将从重点研究中受益的目标领域:(1)确定宿主防御策略(抗性和耐受性)以及蛙壶菌致病性特征的遗传基础;(2)对驱动宿主-病原体相互作用季节性和/或时间模式的适应性变化进行基因组表征。为了深入了解宿主的生存情况,我们回顾了近期的文献——包括实验性蛙壶菌挑战和纵向研究——这些研究强调了由遗传和环境因素共同决定的蛙壶菌感染的复杂性。鉴于疾病结果的异质性和宿主物种的广泛多样性,两栖动物为识别对一种新出现的真菌病原体抗性的新遗传决定因素提供了独特的机会。开发更多的遗传资源(例如,基因组图谱、抗性定位和双RNA测序)将推动我们对在不同环境中作用于受感染宿主的先天和适应性免疫系统组成部分的理解。这些生态免疫经济学应用将宿主-病原体生态进化过程与应用保护措施联系起来,将特别有利于仍在圈养种群中得到保护的濒危两栖动物。

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