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

因为突变的过程会随机引入新的遗传变异，所以人们认为突变率太高会导致种群灭绝。当一个群体的突变率超过这样一个点时，一种被称为错误灾难的现象就会发生，在这个点上，突变的积累超过了保持最适合的基因的自然选择的力量。最近的工作给出了基因组突变率和适应度变化之间的必然关系的定量预测，这将导致错误灾难。在目前的研究中，我们将对一组无性细菌群体进行详细的实验表征，这些细菌群体被设计成具有非常高的突变率。在实验室中观察到这些种群已经下降到灭绝，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结果，即许多无性恋人口的寿命很短。此外，这些结果可能为治疗病毒、细菌感染和癌症的新方法提供基本的科学依据。这项研究具有新颖性，因为它是第一次对误差突变进行良好控制的实验检验。这个项目与几个广泛的影响有关。两名本科生和一名高中生对初步结果做出了贡献。目前，宾夕法尼亚大学的一名本科生直接参与了相关研究。此外，我们系正在启动一项试点计划，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两个部分，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-S论文项目提供基础，该项目最终可能会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.