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

由于突变过程随机引入了新的遗传变异，人们一直认为，过高的突变率将导致种群灭绝。据预测，当一个种群的突变率超过突变积累超过自然选择维持最适基因型的力量时，就会出现一种被称为错误灾难的现象。最近的研究对种群中基因组突变率和适应度变异之间的必要关系进行了定量预测，这将导致误差突变。在目前的研究中，我们将对一组具有极高突变率的无性细菌种群进行详细的实验表征。这些种群在实验室中被观察到减少到灭绝，这表明发生了错误灾难。这一结果可能有助于解释长期以来的观察，即许多无性种群寿命很短。此外，这些结果可能为治疗病毒和细菌感染以及癌症的新方法提供基本的科学依据。这项研究的新颖之处在于，它是第一个控制良好的误差突变实验测试。这个项目有几个广泛的影响。两名本科生和一名高中生对初步结果做出了贡献。目前，美国宾夕法尼亚大学有一名本科生直接参与相关研究。此外，我们系正在开展一项试点计划，让当地高中生在实验室进行研究。这个项目结合了理论和实验的组成部分，不同背景的学生可能会感兴趣。这个项目的结果可能会为另一个本科生提供基础？S的论文项目，最终可能产生发表的研究成果。

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.