BRC-BIO: Exploring the genetic basis of adaptation through convergent dietary specialization in mammals

就像人类有许多不同的美食一样，其他哺乳动物也有广泛不同的饮食偏好，从在大草原上吃草的羚羊到在北极捕食最肥的海豹的北极熊。我们对这些不同的饮食是如何进化的以及为什么进化的知之甚少，特别是关于允许哺乳动物吃这么多不同食物的基因变化。这个研究项目将首先使用来自许多来源的信息来定义哺乳动物的饮食。这些来源包括对野生哺乳动物的观察，博物馆标本的测量，以及动物肠道中细菌的信息。然后，研究人员将把这些特定的饮食定义与哺乳动物的DNA序列信息结合起来，以确定与不同饮食进化有关的基因。最后，研究人员将通过实验来展示不同哺乳动物基因的变化如何影响细胞处理其饮食成分的能力。这项工作将确定对哺乳动物适应环境很重要的新基因。它将展示这些基因的变化是如何让哺乳动物处理不同食物的。该项目还将扩大历史上被排除在K12和本科水平之外的群体对基因组学和生物信息学研究的参与。来自代表性不足背景的本科生将与其他科学家一起开展这项研究。PI还将与当地高需求学校的K12教师合作，开展能够将基因组数据带入教师课堂的活动。将基因组和环境变化联系起来是理解适应过程的关键。趋同表型的研究，提供了相同的适应过程的独立复制，对识别适应的基因组变化具有特别的希望。在具有相同适应性状的多个独立谱系中，观察相同遗传位点上的适应分子特征可以暗示这些位点对该性状有贡献。该建议使用这些特征来识别与趋同哺乳动物饮食变化相关的基因组变化。具体来说，该研究将严格定义代表哺乳动物饮食差异的定量表型。它将确定哺乳动物定量饮食表型选择的基因和基因家族。最后，这项工作将证明代谢基因参与饮食适应的细胞机制。PI的实验室将利用公开的数据，确定最可变的定量饮食维度与哺乳动物系统发育中基因和基因家族的进化速度之间的联系。为了确定观察到的特定代谢基因的进化变化对功能的影响，实验室将测试酿酒酵母中不同物种的同源物的代谢效应。哺乳动物的饮食适应涉及高度保守的细胞内代谢途径的变化，这些途径符合这些功能测定。通过这项工作产生的方法、发现和资源将为未来在进化时间尺度上对环境适应的基因组基础研究提供基础。该奖项反映了美国国家科学基金会的法定使命，并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，被认为值得支持。

Just as humans have many different cuisines, other mammals also have widely diverse dietary preferences, from antelope grazing the savannahs to polar bears hunting the fattest seals in the Arctic. We know very little about how and why these different diets have evolved, particularly about the genetic changes that allow mammals to eat so many different foods. This research project will first define mammalian diets using information from many sources. These sources include observations of mammals in the wild, measurements from museum specimens, and information about bacteria in animals’ guts. The researchers will then combine these specific dietary definitions with information about mammals’ DNA sequences to identify genes that are involved in the evolution of different diets. Finally, the researchers will use experiments to show how changes in different mammals’ genes affect cells’ ability to process components of their diets. This work will identify new genes that are important for mammals to adapt to their environments. It will show how changes in these genes have allowed mammals to process different foods. The project will also expand participation in genomics and bioinformatics research by historically excluded groups at both the K12 and undergraduate levels. Undergraduates from underrepresented backgrounds will work together with other scientists to carry out the research. The PI will also collaborate with K12 teachers in local high-need schools to develop activities that can bring genomic data into the teachers’ classrooms.Connecting genomic and environmental changes is key to understanding how adaptation proceeds. The investigation of convergent phenotypes, which provide independent replicates of the same adaptive process, holds particular promise for identifying genomic changes underlying adaptation. Observing molecular signatures of adaptation at the same genetic loci in multiple independent lineages with the same adaptive trait can implicate these loci as contributing to this trait. This proposal uses such signatures to identify genomic changes associated with convergent mammalian dietary changes. Specifically, the research will rigorously define quantitative phenotypes representing dietary variation across mammals. It will identify genes and gene families underlying selection on quantitative dietary phenotypes across mammals. Finally, the work will demonstrate the cellular mechanisms of metabolic genes involved in dietary adaptation. The PI’s lab will identify associations between the most variable quantitative dietary dimensions and the evolutionary rates of genes and gene families across the mammalian phylogeny, using publicly available data. To determine the functional impacts of observed evolutionary changes in specific metabolism genes, the lab will test the metabolic effects of different species’ orthologs in S. cerevisiae. Mammalian dietary adaptation involves changes in highly conserved intracellular metabolic pathways that are amenable to these functional assays. The methods, findings, and resources generated through this work will provide a foundation for future studies on the genomic basis of environmental adaptation across evolutionary timescales.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.