OPUS: MCS: The importance of mitochondrial and structural mutations in generating fitness variance in the ciliate Tetrahymena

基因突变有很多种，它们会对生物体的适应性产生不同的影响。例如，改变基因内DNA碱基对的小突变可能与改变基因拷贝数的突变产生不同的影响。这项研究将揭示一个基本问题：不同类型的基因突变如何促进地球上巨大的生物多样性的进化？令人惊讶的是，这个问题的答案仍然不清楚。在对单细胞生物的研究中，这项研究将发现不同类型的突变发生的速度，并观察这些突变对生物适应性的影响。本研究结果将有助于阐明突变过程及其在多样性产生中的作用。这项研究将使一名处于职业生涯中期的科学家和几名未被充分代表的少数民族和第一代大学生接受现代基因组方法的培训成为可能。先前对微生物真核生物（纤毛虫嗜热四膜虫）突变积累的研究显示，碱基取代突变率惊人地低。这个比率如此之低，以至于它无法解释在实验过程中观察到的适应性变化，这表明一定有其他类型的突变导致了观察到的适应性变化。为了确定不同类型的突变在产生适应度方差中的相对重要性，本研究将利用这些先前产生的突变积累系，测量嗜热T.的碱基取代率、结构变化率和线粒体变化率。对这些品系进行的新的基因组分析将确定哪种类型的突变最频繁，并通过与表型数据的比较，确定哪种类型有可能在与健康相关的性状中产生最大的变异。这些分析的结果将提供有价值的洞察突变的类型最负责进化的新颖性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

There are many types of genetic mutations and they can have different effects on an organism's fitness. For example, small mutations that change DNA base pairs within a gene may have different effects than mutations that change the number of copies of a gene. This research will shed light on the fundamental question: how do different types of genetic mutations contribute to the evolution of the enormous biodiversity found on earth? Surprisingly, the answer to this question remains unclear. In studies of a unicellular organism, this research will find the rate at which different types of mutations happen and look at the effects of these mutations on organisms' fitness. The results of this research will help to clarify the process of mutation and its role in generating diversity. This research will make possible the training in modern genomic methods of a mid-career scientist and several underrepresented minority and first-generation college students.Previous studies of mutation accumulation in a microbial eukaryote, the ciliate Tetrahymena thermophila, revealed a surprisingly low base-substitution mutation rate. This rate was so low that it could not account for the observed changes in fitness over the course of an experiment, indicating that there must be other types of mutations responsible for the observed changes in fitness. To determine the relative importance of different types of mutations in generating fitness variance, this research will measure the rates of base-substitution, structural, and mitochondrial mutations in T. thermophila, using these previously generated mutation accumulation lines. New genomic analyses of these lines will determine which types of mutations are most frequent and, by comparison to phenotypic data, will determine which types have the potential to generate the most variance in fitness-related traits. The results of these analyses will provide valuable insight into the types of mutations most responsible for evolutionary novelty.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.