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

基因突变有多种类型，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会与改变基因拷贝数的突变产生不同的影响。这项研究将阐明一个基本问题：不同类型的基因突变如何有助于地球上发现的巨大生物多样性的进化？令人惊讶的是，这个问题的答案仍然不明朗。在对单细胞生物体的研究中，这项研究将找出不同类型突变发生的速度，并观察这些突变对生物体适应性的影响。这项研究的结果将有助于阐明突变的过程及其在产生多样性中的作用。这项研究将使一名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进行现代基因组方法的培训成为可能。以前对微生物真核生物-嗜热四膜虫突变积累的研究显示，碱基替换突变率令人惊讶地低。这一比率如此之低，以至于无法解释在实验过程中观察到的健康状况的变化，这表明一定有其他类型的突变导致了观察到的健康状况的变化。为了确定不同类型的突变在产生适合度差异中的相对重要性，本研究将使用这些先前产生的突变累积系来测量嗜热梭菌的碱基替换率、结构突变率和线粒体突变率。对这些品系的新基因组分析将确定哪些类型的突变最频繁，并且通过与表型数据的比较，将确定哪些类型有可能在与适应度相关的性状中产生最大的变异。这些分析的结果将提供对导致进化新颖性的最有价值的突变类型的洞察。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.