URoL: Epigenetics 2: Collaborative Research: Bumble bee cold tolerance across elevations - From epigenotype to phenotype across space, time, and levels of biological organization

了解生物如何科普环境的变化是生态学和进化生物学的基本重要性。对环境变化的适应通常是通过研究生物体的外观（表型）及其DNA序列（基因型）如何在广泛的气候条件下变化来推断的。然而，人们越来越多地认识到，基因组-表型谱中沿着的其他复杂层通过改变遗传变异的表达来影响对环境的反应。表观遗传学或非DNA序列为基础的DNA修饰在不同的环境条件下越来越被认为是一种有效的机制，可以驱动生物体如何响应不同的环境。同样，与代谢活动相关的不同分子（代谢组）可以在不同环境中的个体或群体之间变化，或者可以在压力条件下改变以改变生物体功能。跨越海拔的物种在短空间尺度上经历了条件的快速变化，特别是温度，这为梳理不同机制如何影响环境变化的耐受性提供了优势。该项目将重点关注野生和实验室饲养的熊蜂的热耐受性，熊蜂是受环境压力威胁的重要传粉者群体。该项目将提供有价值的工具来了解蜜蜂种群如何克服环境压力，这将有助于预测蜜蜂种群的稳定性。亚拉巴马大学、塔斯卡卢萨大学和怀俄明州大学的博士后研究员、研究生和本科生将接受分子生物学、生理学和计算建模方法方面的广泛培训。将为K-12学生开发一个战略游戏应用程序，演示分子变化如何在不同的热条件下影响种群和生态系统。 研究结果将通过在犹他州斯托克斯自然中心内的一个本地蜂园举办的展览来传播，以提高人们对野生传粉者的认识。该项目的主要研究目标是解决这样一个问题：遗传和表观遗传变异的信息如何通过表达这些信息来产生适应非生物极端条件的种内表型？热生理学实验场收集和实验室饲养的熊蜂海拔梯度在俄勒冈州喀斯喀特山脉将结合基因组，转录组，甲基组学和代谢组学分析。将采用计算建模来整合数据集，并测试不同人群中DNA表观遗传修饰的变化如何影响基因表达，并最终影响低温暴露下的生理学。具体的研究问题包括：（1）无论地理来源如何，熊蜂是否能够承受类似的冷应激暴露，或者个体、社会种姓和种群是否表现出与当地气候相关的耐寒性的组成性变异？(2)种群在何种程度上表现出DNA甲基化、转录和代谢组学的结构性变异，而不是对冷应激反应过程的可塑性调节？以及（3）个体生物体内的表观遗传变化如何影响转录，进而影响小分子的产生，以解释个体、种姓、群体和环境之间的耐寒性差异？该奖项反映了NSF的法定使命，并被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

Understanding how organisms cope with environmental variability is of fundamental importance in ecology and evolutionary biology. Adaptation to environmental variation has commonly been inferred by examining how the appearance of organisms (phenotypes) and their DNA sequences (genotypes) vary across a broad range of climatic conditions. However, there has been increasing recognition of additional layers of complexity along the genome-to-phenotype spectrum that influence responses to the environment by altering expression of genetic variation. Epigenetic, or non-DNA sequence based, DNA modifications under different environmental conditions are increasingly considered to be a potent mechanism that may drive how organisms respond to different environments. Likewise, the different molecules associated with metabolic activity (metabolome) can vary among individuals or populations in different environments or can change under stressful conditions to alter organism function. Species that occur across altitudes experience rapid shifts in conditions, especially temperature, over short spatial scales, which provides advantages for teasing apart how different mechanisms influence tolerance of environmental variation. This project will focus on thermal tolerance across elevations in wild and laboratory reared bumble bees, an important group of pollinators that are threatened by environmental pressures. The project will provide valuable tools to understand how bee populations overcome environmental stress that will help predict the stability of bee populations. Post-doctoral fellows, graduate students and undergraduates at the University of Alabama, Tuscaloosa and University of Wyoming will be broadly trained in molecular biology, physiology and computational modeling approaches. A strategy game app to demonstrate how molecular changes can affect populations and ecosystems under different thermal conditions will be developed for K-12 students. Results of the study will be disseminated through an exhibit at a native bee garden within the Stokes Nature Center in Utah to increase awareness of wild pollinators.The major research goal of the project is to address the question: How does information flow from genetic and epigenetic variation through expression of this information to produce intraspecific phenotypes adapted to abiotic extremes? Thermal physiology experiments on field-collected and laboratory-reared bumble bees from elevation gradients in the Oregon Cascade Mountains will be combined with genomic, transcriptomic, methylomic, and metabolomic analyses. Computational modeling will be employed to integrate data sets and test how variation in epigenetic modification of DNA in different populations influences gene expression, and ultimately physiology, under cold temperature exposure. Specific research questions include: (1) are bumble bees capable of withstanding similar cold stress exposure regardless of geographic origin, or do individuals, social castes, and populations exhibit constitutive variation in cold tolerance associated with local climate? (2) to what degree do populations exhibit structured variation in DNA methylation, transcription, and metabolomics across environments versus plastic regulation of processes in response to cold stress?, and (3) how do epigenetic changes within individual organisms influence transcription and in turn production of small molecules to explain variation in cold tolerance across individuals, castes, colonies, and environments?This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.