Collaborative Research: The impact of reproduction on the tempo and pattern of mitonuclear adaptation

该项目旨在了解核和线粒体基因组如何促进适应性进化，并辨别有性繁殖对这一过程的影响。大多数非微生物生命形式的细胞都含有大量线粒体，线粒体是负责产生生物能量的细胞器。线粒体包含它们自己的基因组，这些基因组比“普通”核基因组要小得多，并编码一组与能量代谢有关的独特基因。线粒体的正常功能依赖于核基因组编码的许多基因产物。因此，这两个基因组必须协同进化，即有丝分裂共同进化。这项研究将首次全面评估在不同生殖系统下伴随着受控的适应性进化的核和线粒体基因组变化。它还将导致发现抑制有丝分裂核损伤影响的新突变。该项目将为科学界提供重要的数据和资源，扩大私人投资机构的教育和外联活动，并为博士后研究员、研究技术员以及研究生和本科生提供研究培训和专业发展。线粒体基因组分析长期以来一直被用于法医学和系统发育应用，线粒体基因组的缺陷与大约1000种人类遗传病、癌症和衰老有关。线粒体遗传学和有丝分裂核相互作用对不同生物学研究领域的核心重要性表明，这项研究将产生深远的影响。这项研究将提供第一次直接的、非回溯性的主要假设检验，以解释有丝分裂核基因组的共同进化。该项目将应用线虫的实验基因组学来研究线粒体电子传输链(ETC)的进化过程，线粒体电子传输链的正常运作依赖于维持有利的有丝分裂核上位相互作用。该项目将：1)确定性系统对有丝分裂适应的节奏和模式的影响。含有有害的线粒体和核编码ETC突变的线虫菌株将在经历专性自交、兼性异交或专性异交的复制种群中进行适应，2)决定单个有丝分裂核突变的进化动力学、功能特征和性别特异性影响。基因组、生物信息学和表型分析将确定可用于掩盖有害ETC突变影响的线粒体和核突变的分子基础和功能基础，并揭示异交率和有丝分裂核适应之间的关系。该奖项反映了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。

This project aims to understand how nuclear and mitochondrial genomes contribute to adaptive evolution, and to discern the impact of sexual reproduction on this process. The cells of most non-microbial life forms contain numerous mitochondria, organelles responsible for generating biological energy. Mitochondria contain their own genomes, which are far smaller than "regular" nuclear genomes and encode a unique set of genes related to energy metabolism. Proper mitochondrial functioning relies upon many gene products encoded by the nuclear genome. These two genomes must therefore evolve in concert; i.e., mitonuclear coevolution. This research will provide the first comprehensive assessment of nuclear and mitochondrial genomic change accompanying controlled, adaptive evolution under different reproductive systems. It will also result in discovery of novel mutations that suppress the effects of mitonuclear damage. The project will provide important data and resources to the scientific community, expand the PIs' educational and outreach activities, and provide research training and professional development for a postdoctoral fellow, a research technician, and graduate and undergraduate students. Analysis of mitochondrial genomes has long been used for forensic and phylogenetic applications, and defects in mitochondrial genomes are implicated in approximately 1,000 human genetic diseases, cancer and aging. The central importance of mitochondrial genetics and mitonuclear interaction to diverse areas of biological research suggest that this research will have far-reaching impacts.This research will provide the first direct, non-retrospective tests of major hypotheses to explain mitonuclear genome coevolution. The project will apply experimental genomics with Caenorhabditis elegans nematodes to study evolutionary process within the context of the mitochondrial electron transport chain (ETC), the proper functioning of which relies on the maintenance of favorable mitonuclear epistatic interactions. The project will: 1) Determine the impact of sexual system on the tempo and patterns of mitonuclear adaptation. C. elegans strains containing deleterious mitochondrial- and nuclear-encoded ETC mutations will undergo adaptation in replicate populations experiencing obligate selfing, facultative outcrossing, or obligate outcrossing, and 2) Determine the evolutionary dynamics, functional characteristics and sex-specific effects of individual mitonuclear mutations. Genomic, bioinformatic and phenotypic analyses will determine the molecular bases and functional underpinnings of mitochondrial and nuclear mutations available to mask the effects of deleterious ETC mutations, and reveal the relationship between rates of outcrossing and mitonuclear adaptation.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.