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

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会完整地从父母传给后代。因此，线粒体应该特别容易积累有害的突变。然而，线粒体已经保持了它们的功能超过10亿年;如何以及为什么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，即一些蜗牛谱系将它们的核和线粒体基因组传递给它们的后代，而没有任何遗传改组;这一过程加速了这些蜗牛中突变的积累。相比之下，在同一蜗牛物种的其他谱系中，父母和后代之间的遗传物质会发生洗牌。这个项目将比较不同的蜗牛谱系，有些有基因改组，有些没有。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突变。减少有害突变的影响对于保持生物体健康至关重要。反过来，健康的生物体可以防止种群灭绝。线粒体中的有害突变有可能被核基因的突变所补偿。这一假设也将在本研究中得到验证。由于功能性线粒体对许多生物体的健康很重要，因此这项研究将与生物医学和农业社区有关。这项研究还将培养新一代科学家，扩大生物学的参与。更广泛的影响包括与高中学生和博物馆的合作。该项目还将与国家科学教育中心（National Center for Science Education）建立获奖的合作伙伴关系，并将其扩展到新的受众。该研究结合了遗传和功能方法，以测试新西兰淡水蜗牛Potamopyrgus antipodarum的细胞核协同进化特征。在这个蜗牛系统中，有些谱系是有性的，有些是无性的。对于这项研究至关重要的是，P. antipodarum的无性谱系比有性谱系具有更高的线粒体替代率。线粒体替代率的这种对比允许该研究的两个目标。目的1将测试的假设，较高的线粒体替代率在无性与有性谱系驱动更强的线粒体-核分子的共同进化动力学。这些共同进化动力学的一个预测是，由核基因组编码的蛋白质的替代率，然后靶向线粒体将高于控制核基因组的替代率。目的2将测试线粒体相互作用对线粒体呼吸和蜗牛代谢率的功能影响。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细胞核相互作用。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。

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.