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

由于突变过程会随机引入新的遗传变异，人们一直认为过高的突变率会导致种群灭绝。当一个种群的突变率超过了突变积累压倒自然选择的力量以维持最适合的基因型的点时，预计会发生一种被称为错误灾难的现象。最近的工作给出了一个定量预测的必要关系，基因组突变率和适应度的变化，在人口中，将沉淀错误灾难。 在目前的研究中，我们将对一组经过工程改造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下降到灭绝，这表明发生了错误灾难。 这些结果可能有助于解释长期以来的观察结果，即许多无性繁殖的种群是短命的。 此外，这些结果可能为治疗病毒和细菌感染和癌症的新方法提供基础科学依据。这项研究是新颖的，因为它是第一个控制良好的实验测试的错误灾难。 该项目与几个广泛的影响有关。 两名本科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名本科生直接参与了相关研究。 此外，我们系正在开展一项试点计划，使当地高中生能够在实验室进行研究。 该项目结合了理论和实验部分，不同背景的学生可能会感兴趣。 这个项目的结果将有可能为另一个本科生提供依据？的论文项目，最终可能会产生出版的研究。

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.