The fitness landscape of genes and proteins

基因和蛋白质的适应度景观

• 批准号: 0950939
• 负责人: Marc Ostermeier
• 金额: $ 67.56万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0950939&HistoricalAwards=false
• 关键词: fitness; landscape; genes; proteins

The occurrence of mutations and their ability to provide an organism with a competitive advantage is central to evolution. Mutations that provide an advantage are relatively rare. The frequency and magnitude of positive, neutral and negative mutational effects is important for the dynamics and outcome of evolutionary processes; however, this distribution of mutational effects has not been comprehensively determined due to experimental limitations. This lack of knowledge has been a major hurdle for the study of how genes and proteins evolve. In this work, engineered bacteria that function analogous to an electrical circuit called a band-pass filter, together with the extensive use of the latest DNA sequencing technology, will be used to determine the distribution of mutational effects for all possible single nucleotide substitutions in a single gene that plays an important role in the evolution of antibiotic resistance. This knowledge will be exploited to address fundamental questions in evolution and practical issues in the application of evolution to biotechnology. Graduate students involved in this research will train undergraduates and high school students through their participation in this project.

突变的发生及其提供具有竞争优势的有机体的能力对于进化至关重要。提供优势的突变相对罕见。正，中性和负突变效应的频率和大小对于进化过程的动态和结果很重要。但是，由于实验局限性，这种突变效应的分布尚未得到全面确定。缺乏知识一直是研究基因和蛋白质如何发展的主要障碍。 在这项工作中，将使用类似于称为带通滤波器的电路的工程细菌，以及最新的DNA测序技术的广泛使用，将用于确定单个基因中所有可能的单个核苷酸取代的突变效应的分布，在单个基因中在抗生素抗性的演化中起着重要作用。 这些知识将被利用，以解决进化进化中的进化和实际问题中的基本问题。参与这项研究的研究生将通过参与该项目培训本科生和高中生。