DISSERTATION RESEARCH: Testing for declining fitness and error catastrophe in adapting asexual populations

论文研究：测试适应无性种群的适应性下降和错误灾难

• 批准号: 1110202
• 负责人: Paul Sniegowski
• 金额: $ 1.34万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1110202&HistoricalAwards=false
• 关键词: DISSERTATION; RESEARCH; Testing; declining; fitness

Because the process of mutation introduces new genetic variation at random, it has been thought that too high a mutation rate will cause a population to go extinct. A phenomenon known as error catastrophe is predicted to occur when the mutation rate of a population surpasses the point at which the accumulation of mutations overpowers the strength of natural selection to maintain the fittest genotype. Recent work gives a quantitative prediction for the necessary relationship between genomic mutation rate and fitness variation in a population that will precipitate error catastrophe. In the current study we will conduct a detailed experimental characterization of a set of asexual bacterial populations engineered to have extraordinarily high mutation rates. These populations have been observed to decline to extinction in the laboratory, suggesting the occurrence of error catastrophe. The results may help explain the longstanding observation that many asexual populations are short-lived. In addition, the results may provide a basic science rationale for novel approaches to the treatment of viral and bacterial infections and cancers. This research is novel in that it is the first well-controlled experimental test of error catastrophe. This project is associated with several broad impacts. Two undergraduates and a high school student have contributed to the preliminary results. At present, one undergraduate at the University of Pennsylvania is directly involved in related research. Additionally, a pilot program is being launched in our department which will expose local high school students to research in the laboratory. This project combines both theoretical and experimental components that students of varying backgrounds may take interest in. The results of this project will likely may provide the basis for another undergraduate student?s thesis project which may ultimately produce published research.

由于突变过程是随机引入新的遗传变异，因此人们认为太高的突变率会导致人群灭绝。当种群的突变速率超过突变积累超越自然选择的强度以维持最合适的基因型的强度时，预计将发生一种称为误差灾难的现象。最近的工作对人群中的基因组突变率和适应性变化之间的必要关系进行了定量预测，这将导致误差灾难。 在当前的研究中，我们将对一组具有非常高的突变率的无性细菌种群进行详细的实验表征。已经观察到这些人群在实验室中拒绝灭绝，这表明发生了误差灾难。 结果可能有助于解释以下长期观察，即许多无性群体都是短暂的。 此外，结果可能为治疗病毒和细菌感染和癌症的新方法提供了基本的科学基本原理。这项研究是新颖的，因为它是误差灾难的首次控制的实验测试。 该项目与一些广泛的影响有关。 两名大学生和一名高中生为初步结果做出了贡献。 目前，宾夕法尼亚大学的一位本科生直接参与了相关研究。 此外，我们部门正在启动一项试点计划，该计划将使当地的高中学生在实验室进行研究。 该项目结合了不同背景的学生可能会引起人们感兴趣的理论和实验组成部分。该项目的结果可能会为另一个本科生的论文项目提供基础，最终可能会产生已发表的研究。