The Physiological Genomics of Diet Switching in Mammalian Herbivores

在每顿饭中，以鹿、牛和兔子等植物(食草动物)为食的动物都面临着被食物中自然产生的有毒化学物质中毒的可能性。然而，食草动物是如何处理天然毒素的，人们仍然知之甚少。例如，人们对控制动物处理植物中潜在有毒化合物能力的特定基因知之甚少。为了解决这些根本问题，这项研究将重点放在一项戏剧性的饮食变化上：林蛙通常吃刺柏和仙人掌，但美国西南部的几个种群已经转向以杂酚油灌木为食。杂色油树丛产生的天然毒素与刺柏和仙人掌有根本的不同，因此专门的林木种群必须以不同于刺柏和食用仙人掌的方式为他们的饮食解毒。该项目的目标是确定与林鼠以杂酚油灌木为食的有毒食物的能力相关的DNA水平变化。该项目将开发新的基因组工具，这将对更广泛的科学界有用。更好地了解动物如何处理毒素也可以影响人类和其他动物的药物开发决策，并影响饲养选择，以提高牛等自由放养的家养食草动物的产量。这项工作的结果将通过犹他州自然历史博物馆关于树木生态的互动展示向公众传达。尽管对模式物种和人类进行了数十年的药理学研究，但哺乳动物草食动物代谢植物次生化合物的机制和适应新饮食的基因组基础仍然知之甚少。这项研究将利用一个戏剧性的饮食变化事件：刺柏(Juniperus spp.)的替代，来研究哺乳动物食草动物饮食适应和专门化的进化。和仙人掌(仙人掌)在食草性林木的食物中加入杂酚油灌木(Larrea Tridentata)。该项目有三个目标：1)确定与瘦小新单胞菌彻底的饮食变化相关的基因组变化。2)在杂酚油日粮中重复涉及相似的遗传途径以实现专门化的试验。3)对杂酚油饲料的亲本种群和杂交种群的转录反应进行了表征。这项拟议的工作利用现代进化基因组学方法来解决生理生态学中一个长期存在的问题：在有毒饮食的处理过程中，哪些机制是重要的？该项目将使人们更深入地了解生物体对环境变化的反应，包括在基因组水平上关于哺乳动物食草动物如何适应饮食毒素的基本信息。该项目专门测试了在两个独立进化出专门研究杂酚油饮食的物种中，是否有相同的基因组区域被选择。将与犹他州自然历史博物馆合作，开发一个关于森林生态及其对社会重要性的互动展示。将开发对更广泛的科学界有用的基因组工具。此外，PI将指导学生(从高中到研究生)和博士后对非模式物种的生理基因组研究。

At every meal, animals that feed on plants (herbivores) such as deer, cattle, and rabbits, face the possibility of being poisoned by naturally-occurring toxic chemicals in their food. Nevertheless, how herbivores process natural toxins remains poorly understood. For example, remarkably little is known about the specific genes that control an animal's ability to process potentially toxic compounds in plants. To address these fundamental problems, this research will focus on a dramatic dietary change: woodrats normally eat juniper and cactus, but several populations in the American southwest have switched to a diet of creosote bush. Creosote bush produces natural toxins that radically differ from juniper and cactus, and therefore the specialized woodrat populations must detoxify their diets differently than the juniper and cactus-eaters. The goal of this project is to identify DNA-level changes that are associated with woodrats' ability to feed on a toxic diet of creosote bush. This project will develop new genomic tools that will be useful to the broader scientific community. A better understanding of how animals process toxins can also impact decisions about pharmaceutical development for humans and other animals, and influence feeding options to improve production of free-ranging domestic herbivores like cattle. Results of this work will be communicated to the public through an interactive display about the ecology of woodrats at the Utah Museum of Natural History. Despite decades of pharmacological research on model species and humans, the mechanisms used by mammalian herbivores to metabolize plant secondary compounds and the genomic basis underlying adaptation to new diets remain poorly understood. This research will investigate the evolution of dietary adaptation and specialization in mammalian herbivores by capitalizing on a dramatic diet change event: the replacement of juniper (Juniperus spp.) and cactus (Opuntia spp.) with creosote bush (Larrea tridentata) in the diets of herbivorous woodrats. The project has three goals: 1) Identify genomic changes associated with a radical dietary shift in Neotoma lepida. 2) Test for the repeated involvement of similar genetic pathways for specialization on creosote diets in N. bryanti. 3) Characterize the transcriptomic response of parental and hybrid populations of N. lepida and N. bryanti to a creosote diet. The proposed work leverages modern evolutionary genomic approaches to address a long-standing question in physiological ecology: which mechanisms are important in the processing of toxic diets? The project will lead to a deeper understanding of the responses of organisms to changes in the environment, including fundamental information at the genomic level about how mammalian herbivores adapt to dietary toxins. The project specifically tests whether the same genomic regions are under selection in two species that independently evolved the ability to specialize on creosote diets. An interactive display about the ecology of woodrats and their importance to society will be developed in collaboration with the Utah Museum of Natural History. Genomic tools will be developed that will be useful to the broader scientific community. In addition, the PIs will mentor students (high school through graduate) and postdocs in physiological genomics research on non-model species.