DISSERTATION RESEARCH: Alcohol dehydrogenase in Drosophila: Functional characterization of adaptive genetic variation

论文研究：果蝇中的乙醇脱氢酶：适应性遗传变异的功能特征

• 批准号: 1501877
• 负责人: Joseph Thornton
• 金额: $ 1.93万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1501877&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; Alcohol; dehydrogenase; Drosophila

How organisms adapt to environments is a fundamental question in biology, and exploring this process can enrich our understanding of factors that shape the evolution of forms, functions, and species. A precise way to study adaptive traits is by experimentally characterizing the mechanisms through which genes drive evolution. This approach can reveal general principles about how changes at the DNA level affect function over time. Here, this framework is used to rigorously characterize alcohol tolerance in fruit flies, a classic model of adaptive evolution. The researchers will investigate a long-standing hypothesis about adaptation to ethanol and the relationship of variation at genetic, biochemical, and physiological levels. This work will demonstrate how biochemical methods can be deployed in evolutionary contexts to yield novel insights. Broader impacts of this project include training of a graduate student in the emerging discipline of evolutionary biochemistry as well as collaboration with local high school teachers to design, present, and publicly distribute an educational module emphasizing the interface of biochemistry and evolutionary genetics. The evolution of alcohol dehydrogenase (ADH) in Drosophila melanogaster is an iconic example of adaptation: inter- and intraspecific variations in ADH harbor signatures of positive and balancing selection, respectively, and past works have hypothesized the responsible selective forces. The signature of positive selection on ADH is thought to reflect protein evolution in response to expansion and adaptation to ethanol-rich environments by D. melanogaster. This research utilizes ancestral sequence reconstruction of proteins, biochemical characterization, and physiological assays of transgenic organisms to test if functional changes occurred in ADH as predicted. The signature of balancing selection - supported by recurrent and dynamic allele frequency clines across continents - is thought to be due to allele-by-temperature interactions. This project investigates the role of temperature interactions as a mechanism. It will test a hypothesis about how temperature might shape patterns of genetic variance by characterizing the propensity of natural alleles to misfold at environmentally realistic temperatures. These experiments will have broad significance as methodological exemplars of utilizing detailed, mechanistic studies in evolutionary contexts to elucidate general insights pertaining to the functional determinants of adaptation.

生物如何适应环境是生物学中的一个基本问题，探索这一过程可以丰富我们对形成形式、功能和物种进化的因素的理解。研究适应性性状的一种精确方法是通过实验表征基因驱动进化的机制。这种方法可以揭示DNA水平的变化如何随时间影响功能的一般原理。在这里，这个框架被用于严格表征果蝇的酒精耐受性，这是一种经典的适应进化模型。研究人员将调查一个长期存在的关于乙醇适应性的假设，以及在遗传、生化和生理水平上的变异关系。这项工作将展示如何生化方法可以部署在进化背景下产生新的见解。该项目的更广泛影响包括培训一名研究生学习进化生物化学这一新兴学科，以及与当地高中教师合作设计、呈现并公开发布强调生物化学和进化遗传学界面的教育模块。黑腹果蝇酒精脱氢酶（ADH）的进化是适应的一个标志性例子：ADH的种间和种内变化分别具有积极选择和平衡选择的特征，过去的研究假设了负责的选择力。ADH的正选择特征被认为反映了D. melanogaster对扩张和适应富含乙醇环境的蛋白质进化。本研究利用蛋白质的祖先序列重建、生化表征和转基因生物的生理分析来测试ADH是否如预测的那样发生了功能变化。平衡选择的特征——由跨大陆的周期性和动态等位基因频率曲线支持——被认为是由于等位基因与温度的相互作用。本项目研究温度相互作用作为一种机制的作用。它将通过描述自然等位基因在环境实际温度下错误折叠的倾向，来测试一个关于温度如何影响遗传变异模式的假设。这些实验将具有广泛的意义，作为在进化背景下利用详细的机制研究来阐明与适应的功能决定因素有关的一般见解的方法论范例。