Mitonuclear Interaction and the Genetic Architecture of Phenotypic Evolution

该项目将评估线粒体功能障碍和线粒体-核相互作用如何在生物组织的三个层次-分子遗传，细胞和有机体-上促进进化。PI将在线粒体电子传递链（ETC）的背景下研究进化过程。使用ETC缺陷型秀丽隐杆线虫的进化实验将与全基因组测序，生物信息学和线粒体表型相结合，以研究适应不良和补偿性适应性进化的遗传基础-自然选择的过程有利于基因座的变化，以补偿突变等位基因的有害影响。ETC对真核生物至关重要，其正常功能依赖于维持有利的线粒体相互作用;因此，它是研究两种进化形式的模式和功能基础以及突变在塑造线粒体基因组整合中的作用的理想选择。此外，ETC功能障碍是全基因组自发突变率变化的一个原因。这项工作将揭示不同形式的ETC损伤对核和线粒体基因组稳定性的影响，以及伴随的线粒体功能和生物体适应性的变化。由于很少有研究已经解决了群体水平的后果的补偿突变或补偿进化的遗传机制在真核系统中，因为线粒体代谢和ETC功能是高度进化保守的，这些发现预计将是广泛的兴趣和相关的其他真核生物。该项目将在尖端基因组学研究方面培训学生，为科学界提供重要的数据和资源，并扩大PI的教育和推广活动。少数民族和其他学生获得有意义的研究和科学教育经验。PI将共同培训研究生和本科生，参与少数民族学生团体和当地美洲原住民高中的科学推广活动，并根据波特兰州立大学和俄勒冈州州立大学各自本科遗传学课程的研究开发生物信息学学习模块。

This project will evaluate how mitochondrial dysfunction and mitochondrial-nuclear interaction contribute to evolution across three levels of biological organization - molecular-genetic, cellular, and organismal. The PIs will study evolutionary process within the context of the mitochondrial electron transport chain (ETC). Evolution experiments using ETC-deficient Caenorhabditis elegans nematodes will be combined with whole-genome sequencing, bioinformatics and mitochondrial phenotyping to study the genetic bases of maladaptive and compensatory adaptive evolution - the process whereby natural selection favors changes at loci that compensate for the deleterious effects of a mutant allele. The ETC is crucial for eukaryotic life and its proper functioning relies on the maintenance of favorable mitonuclear interactions; it is thus ideal for studying the patterns and functional bases of both forms of evolution and the role of mutation in shaping mitonuclear genome integration. Further, ETC dysfunction is a proposed cause of variation in genome-wide spontaneous mutation rates. This work will reveal the effects of different forms of ETC damage on nuclear and mitochondrial genome stability and concomitant changes in mitochondrial function and organismal fitness. Because few studies have addressed the population-level consequences of compensatory mutation or the genetic mechanisms of compensatory evolution in eukaryotic systems, and because mitochondrial metabolism and ETC function are highly evolutionarily conserved, findings are expected to be of broad interest and relevant to other eukaryotes.Broader Impacts. The project will train students in cutting-edge genomics research, provide important data and resources to the scientific community, and expand both PIs' educational and outreach activities. Minority and other students with gain meaningful research and science education experience. The PIs will co-train graduate and undergraduate students, participate in science outreach to minority student groups and a local Native American high school, and develop bioinformatics learning modules based on the research to be taught in their respective undergraduate Genetics courses at Portland State University and Oregon State University.