Mitochondrial effects on male and female fitness in the copepod Tigriopus californicus

该项目测试了一种假设，即伤害男性的突变可以在基因组的某些部分积累，即线粒体，而线粒体只通过雌性系遗传。这些对男性有害的突变不会被移除，因为作用于男性的自然选择的影响不会传递给下一代。大多数熟悉的生物都有一个大的基因组，位于它们的细胞核中，这是从双亲那里遗传来的，外加线粒体中的一个小基因组。线粒体是每个细胞的电池，只能从母亲那里遗传。线粒体基因产物与核基因产物相互作用，执行重要的生命功能。据预测，危害男性的突变将在线粒体基因组中积累，并导致它们的适合度降低。该项目将研究细胞核和线粒体基因组之间的相互作用，以及对小型海洋贝类恐龙的雄性和雌性适应性的影响。结果将测试假设的对男性健康的负面影响是否普遍存在，并检查核-线粒体相互作用是否以及如何影响这些影响。这一假设对针对性别的医学干预具有深远的影响，因为有害的线粒体突变与男性不育、糖尿病、心肌病和男性耳聋等疾病以及整个衰老过程有关。除了研究本身，该项目还将培养博士后研究员、博士生和本科生。此外，该项目将支持与洛杉矶不同社区的合作，包括与太平洋水族馆(旨在提高公众对进化论的认识)的合作，以及与初中生和高中生的大学项目(旨在加强为未被充分代表的少数群体服务的班级的进化论课程)。将通过创造12个细胞质杂交来评估男性特有的突变负载，在这些杂交中，来自12个不同种群的线粒体将通过大约15代回交被转移到相同的等基因核背景上。这12个品系将包括11个种群间杂交种和一个对照。这12个品系中的每一个都将用于分析特定性别的生育力和整个生命周期(180天以上)的存活率。这些数据将被用来测试线粒体效应的性别差异的程度，测试性别差异是否在生育方面大于寿命，并测试这种性别差异在生命后期和更高的新陈代谢需求下(例如更高的温度)是否会加剧。12个线粒体基因组将被完全测序，从而能够测试具有性别特异性影响的线粒体突变的基因组范围。此外，将评估一个种群间杂交和对照中的基因表达，以确定与性别特有的有丝分裂-核冲突相关的核基因。

This project tests the hypothesis that mutations that harm males, can accumulate in parts of the genome, the mitochondria, that are inherited only through the female line. These male-harming mutations are not removed because the effects of natural selection acting on males are not passed to the next generation. Most familiar organisms have a large genome that resides in the nucleus of their cells, which is inherited from both parents, plus a small genome in the mitochondria. The mitochondria are the batteries of each cell, which are inherited only from the mother. Mitochondrial gene products interact with nuclear gene products to perform critical life functions. Male-harming mutations are predicted to accumulate in the mitochondrial genome and result in their reduced fitness. The project will examine interactions between the nuclear and mitochondrial genomes and the effects on male and female fitness in a small marine shellfish, the copepod Tigriopus californicus. The results will test whether the hypothesized negative effects on male fitness are widespread and examine whether and how the nuclear-mitochondrial interactions impact these effects. This hypothesis has profound implications for sex-specific medical interventions, because harmful mitochondrial mutations are implicated in male infertility, and diseases such as diabetes, cardiomyopathy, and male deafness, as well as in the overall aging process. Beyond the research itself, the project will train a postdoctoral researcher, Ph.D. students and undergraduate researchers. Further, the project will support outreach to diverse Los Angeles communities, including collaborations with the Aquarium of the Pacific (aimed at promoting public awareness of evolution) and with university programs for middle- and high-school students (aimed at enhancing the evolution curriculum in classes serving under-represented minorities). Male-specific mutational load will be assessed by creating 12 cytoplasmic hybrids in which mitochondria from 12 divergent populations will each be transferred onto the same isogenic nuclear background by approximately 15 generations of backcrossing. These 12 lines will include 11 interpopulation hybrids and one control. Each of the 12 lines will be used for assays of sex-specific fertility and survivorship over the full lifespan (180+ days). These data will be used to test the magnitude of the gender gap in mitochondrial effects, to test if the gender gap is larger for fertility than longevity, and to test whether this gender gap is aggravated in later life stages and under higher metabolic demand (e.g. higher temperature). The 12 mitochondrial genomes will be fully sequenced, allowing tests of the genomic extent of mitochondrial mutations with sex-specific effects. Further, gene expression will be assessed in one interpopulation hybrid and the control to identify nuclear genes associated with sex-specific mito-nuclear conflict.