Collaborative Research: Phylogenetics of autoresistance in poison frogs as revealed by phylogenomics, neurophysiology, and comparative ecology

合作研究：通过系统基因组学、神经生理学和比较生态学揭示毒蛙自身抗性的系统发育学

• 批准号: 1556982
• 负责人: Richard Fitch
• 金额: $ 22.36万
• 依托单位: Indiana State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1556982&HistoricalAwards=false
• 关键词: Collaborative; Research; Phylogenetics; autoresistance; poison

Animals have evolved a variety of chemicals defenses against predators. A premier example is the toxic chemicals in the skin of poison frogs. Because these frogs are brightly colored, predators such as birds and snakes learn to avoid them. These toxins are alkaloids, found in many animals and plants. The frogs acquire these chemical defenses by eating ants and other arthropods that contain the alkaloids. These frog alkaloids (e.g., tetrodotoxin, batrachotoxin) are pharmacologically important and cause muscle paralysis, and disrupt breathing and cardiac function. At the cellular level, alkaloids affect ion channels, which control the transmission of nerve impulses. Surprisingly, the ion channels of poison frogs are are not affected by their own toxins; thus, deciphering how this evolved has important broader impacts that translate to human health. This research will use evolutionary trees to guide the activities: fieldwork to acquire and characterize natural alkaloids and collect ecological data on the species, molecular evolution of ion channel resistance to alkaloids, and neurophysiological effects of alkaloids on ion channels. The research will provide opportunities for students from the University of Texas and Indiana State University to jointly participate in international fieldwork, acquire new skills in bioinformatics, molecular modeling, genomics, and neurophysiology, as well as promote interactions between the two universities.The project will use Next-Generation DNA sequencing of transcriptomes, targeted sequencing of hundreds of genes, and bioinformatics methods to reconstruct evolutionary trees that will guide the research program with an experimental framework for explaining the origin of resistance, which has evolved multiple times in the poison frogs (family Dendrobatidae). Sequencing will also be used to identify novel amino acid replacements that may confer resistance to alkaloids. Computational modeling and in vitro assays of mutated ion channels will determine if these novel replacements provide resistance to natural and synthesized alkaloids. Fieldwork will focus on acquiring genetic samples, skin alkaloids, and color photographs from multiple populations of frogs, using natural history collection standards data collection and voucher specimens preparation. The combination of approaches will provide novel insights in the systematics of Dendrobatidae poison frogs, and also the evolution of auto-resistance to toxic alkaloids within the group.

动物已经进化出各种化学物质来抵御掠食者。一个主要的例子是毒蛙皮肤中的有毒化学物质。因为这些青蛙颜色鲜艳，鸟类和蛇等掠食者学会避开它们。这些毒素是生物碱，存在于许多动物和植物中。青蛙通过吃蚂蚁和其他含有生物碱的节肢动物来获得这些化学防御。这些青蛙生物碱（例如，河豚毒素、蛙毒素）是非常重要的，可引起肌肉麻痹，并破坏呼吸和心脏功能。在细胞水平，生物碱影响离子通道，控制神经冲动的传输。令人惊讶的是，毒蛙的离子通道不受它们自身毒素的影响;因此，破译这种进化方式对人类健康具有重要的更广泛的影响。本研究将使用进化树来指导活动：野外工作以获取和表征天然生物碱并收集物种的生态学数据，离子通道对生物碱的抗性的分子进化以及生物碱对离子通道的神经生理学影响。该研究将为德克萨斯大学和印第安纳州州立大学的学生提供机会，共同参与国际实地考察，获得生物信息学，分子建模，基因组学和神经生理学的新技能，以及促进两所大学之间的互动。该项目将使用转录组的下一代DNA测序，数百个基因的靶向测序，和生物信息学方法来重建进化树，这将指导研究计划的实验框架，解释抗性的起源，这已经在毒蛙（家庭Dendrobatidae）多次进化。测序也将用于鉴定可能赋予生物碱抗性的新氨基酸替代。突变离子通道的计算建模和体外测定将确定这些新的替代品是否对天然和合成生物碱具有抗性。实地考察将集中在获取遗传样本，皮肤生物碱，并从多个种群的青蛙彩色照片，使用自然历史收集标准数据收集和凭证标本制备。这两种方法的结合，将为石斛科毒蛙的系统学研究以及毒蛙对有毒生物碱的自身抗性的进化提供新的见解。