The Physiological Genomics of Diet Switching in Mammalian Herbivores

在每一餐中，以植物为食的动物（食草动物），如鹿，牛和兔子，都面临着被食物中天然存在的有毒化学物质中毒的可能性。 然而，对于食草动物如何处理天然毒素，我们仍然知之甚少。例如，人们对控制动物处理植物中潜在有毒化合物的能力的特定基因知之甚少。为了解决这些根本问题，这项研究将集中在一个戏剧性的饮食变化：林鼠通常吃杜松和仙人掌，但在美国西南部的几个种群已经转向了木馏油布什的饮食。杂酚油灌木产生的天然毒素与杜松和仙人掌完全不同，因此专门的林鼠种群必须以不同于杜松和仙人掌的方式解毒。该项目的目标是确定与林鼠以有毒的杂酚油灌木为食的能力相关的DNA水平变化。该项目将开发新的基因组工具，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在犹他州自然历史博物馆举行的关于林鼠生态的互动展示传达给公众。 尽管对模式物种和人类进行了数十年的药理学研究，但哺乳动物食草动物代谢植物次生化合物的机制以及适应新饮食的基因组基础仍然知之甚少。本研究将探讨哺乳动物食草动物的饮食适应和专业化的演变，利用一个戏剧性的饮食变化事件：取代杜松（杜松属）。和仙人掌（Opuntia spp.）与杂酚油灌木（Larrea tridentata）在食草林鼠的饮食。该项目有三个目标：1）确定与Neotoma lepida激进饮食转变相关的基因组变化。 2)测试重复参与相似的遗传途径专门化的杂酚油饮食在N。bryanti。3)描述了N. lepida和N. bryanti到杂酚油饮食。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的一个长期存在的问题：哪些机制在有毒饮食的处理中很重要？该项目将导致更深入地了解生物体对环境变化的反应，包括关于哺乳动物食草动物如何适应饮食毒素的基因组水平的基本信息。该项目专门测试了两个物种的相同基因组区域是否处于选择之下，这两个物种独立进化出专门吃杂酚油的能力。将与犹他州自然历史博物馆合作开发一个关于林鼠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（高中到研究生）和博士后在非模型物种的生理基因组学研究。

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.