Collaborative Research: SG: Genomic and functional tests of mitochondrial-nuclear coevolution

合作研究：SG：线粒体-核协同进化的基因组和功能测试

• 批准号: 1753695
• 负责人: Kristi Montooth
• 金额: $ 9万
• 依托单位: University of Nebraska-Lincoln
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1753695&HistoricalAwards=false
• 关键词: Collaborative; Research; SG; Genomic; functional

Harmful mutations can negatively affect gene, protein, and organism function. In the extreme, the accumulation of harmful mutations can lead to population extinction. The genetic information in mitochondria - the main source of energy production in most complex organisms - is usually passed intact from parents to offspring. Thus, the mitochondria should be especially prone to the buildup of harmful mutations. However, mitochondria have maintained their function for more than one billion years; how and why is an important question in evolutionary biology. This research uses a model snail system to address these questions. It takes advantage of the fact that some lineages of snails pass both their nuclear and mitochondrial genomes on to their offspring without any genetic shuffling; a process that accelerates the accumulation of mutations in these snails. By contrast, there is shuffling of genetic material between parents and offspring in other lineages of the same snail species. This project will compare different lineages of snails, some with genetic shuffling and some without. In doing so, this research will explore how harmful mutations are cleared from populations. Reducing the impact of harmful mutations is important for keeping organisms healthy. In turn, healthy organisms can guard against population extinction. It is possible that harmful mutations in the mitochondria are compensated for by mutations in nuclear genes. This hypothesis will also be tested by this research. Because functional mitochondria are important to the health of many organisms, the research will be relevant to the biomedical and agricultural communities. The research will also train a new generation of scientists and broaden participation in biology. The broader impacts include collaborations with high school students and museums. The project will also extend an award-winning partnership with the National Center for Science Education to new audiences.The research combines genetic and functional methods to test for signatures of mitochondrial-nuclear coevolution in the New Zealand freshwater snail Potamopyrgus antipodarum. In this snail system, some lineages are sexual and others are asexual. Crucially for this study, the asexual lineages of P. antipodarum have higher mitochondrial substitution rates than the sexual lineages. This contrast in mitochondrial substitution rates permits the study's two objectives. Objective 1 will test the hypothesis that higher mitochondrial substitution rates in asexual versus sexual lineages drive stronger mitochondrial-nuclear molecular coevolutionary dynamics. One prediction of these coevolutionary dynamics is that substitution rates for proteins encoded by the nuclear genome that are then targeted to the mitochondria will be higher than the substitution rates in control nuclear gene sets. Objective 2 will test for functional effects of mitonuclear interactions on mitochondrial respiration and snail metabolic rate. Since temperature can impact snail metabolic rates, the second objective will include four different temperature treatments. Results of this research will contribute to our understanding of the mitochondrial-nuclear interactions that define eukaryotes. Furthermore, they are of broad relevance to genome evolution, speciation, and the functional and evolutionary consequences of reproductive mode variation.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.

有害的突变会对基因、蛋白质和生物体功能产生负面影响。在极端情况下，有害突变的积累可能会导致种群灭绝。线粒体是大多数复杂生物体产生能量的主要来源，线粒体中的遗传信息通常原封不动地从父母传给后代。因此，线粒体应该特别容易积累有害的突变。然而，线粒体已经维持其功能超过10亿年；如何以及为什么保持其功能是进化生物学中的一个重要问题。本研究使用模型蜗牛系统来解决这些问题。它利用了这样一个事实，即一些蜗牛血统将它们的核和线粒体基因组同时传递给他们的后代，而不需要任何基因洗牌；这一过程加速了这些蜗牛突变的积累。相比之下，在同一蜗牛物种的其他血统中，父母和后代之间存在遗传物质的洗牌。这个项目将比较不同血统的蜗牛，其中一些有基因洗牌，另一些没有。在这样做的过程中，这项研究将探索如何从人群中清除有害的突变。减少有害突变的影响对保持生物体健康很重要。反过来，健康的有机体可以防止种群灭绝。线粒体中的有害突变可能会被核基因的突变所补偿。这一假设也将通过这项研究得到验证。由于功能线粒体对许多生物的健康很重要，因此这项研究将与生物医学和农业社区相关。这项研究还将培养新一代科学家，并扩大对生物学的参与。更广泛的影响包括与高中生和博物馆的合作。该项目还将与国家科学教育中心的获奖合作伙伴关系扩展到新的受众。这项研究结合了遗传和功能方法来测试新西兰淡水蜗牛Potamopyrgus antipodarum的线粒体-核共同进化的特征。在这个蜗牛系统中，一些血统是有性的，另一些是无性的。对于这项研究来说，至关重要的是，反足拟青霉的无性世系比有性世系具有更高的线粒体替换率。线粒体替代率的这种对比使这项研究的两个目标得以实现。目的1将验证以下假设：无性血统中更高的线粒体替换率比有性血统中更高的线粒体-核分子协同进化动力学。对这些共同进化动态的一种预测是，由核基因组编码的蛋白质的替换率将高于对照核基因组中的替换率，然后这些蛋白质被靶向线粒体。目的2测试有丝分裂核相互作用对线粒体呼吸和钉螺代谢率的功能影响。由于温度会影响蜗牛的代谢率，第二个目标将包括四种不同的温度处理。这项研究的结果将有助于我们理解定义真核生物的线粒体-核相互作用。此外，它们与基因组进化、物种形成以及生殖模式变异的功能和进化后果具有广泛的相关性。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。