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积累在基因组的一部分，即线粒体中，这些线粒体只能通过女性遗传。这些伤害雄性的突变没有被消除，因为自然选择对雄性的影响不会传递给下一代。大多数常见的生物体都有一个大的基因组，位于细胞核中，这是从父母双方遗传的，加上线粒体中的一个小基因组。线粒体是每个细胞的电池，只从母亲那里遗传。线粒体基因产物与核基因产物相互作用以执行关键的生命功能。据预测，伤害男性的突变会在线粒体基因组中积累，并导致其适应性降低。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（桡足类动物Tigriopus californicus）雄性和雌性适应性的影响。研究结果将测试假设的对男性健康的负面影响是否普遍存在，并研究核-线粒体相互作用是否以及如何影响这些影响。这一假说对性别特异性医疗干预具有深远的意义，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体衰老过程有关。除了研究本身之外，该项目还将培养一名博士后研究员、博士学生和本科研究人员。此外，该项目还将支持对不同洛杉矶社区的外联活动，包括与太平洋水族馆合作（旨在提高公众对进化论的认识），以及与针对初中和高中学生的大学方案合作（旨在加强为代表性不足的少数群体服务的班级的进化论课程）。将通过创建12个细胞质杂种来评估雄性特异性突变负荷，其中来自12个不同群体的线粒体将通过大约15代回交各自转移到相同的等基因核背景上。这12个品系将包括11个种群间杂种和1个对照。12个品系中的每一个将用于整个寿命（180天以上）内的性别特异性生育力和存活率测定。这些数据将用于测试线粒体效应中性别差距的大小，测试生育能力的性别差距是否大于寿命，并测试这种性别差距是否在生命后期和更高的代谢需求下加剧（例如更高的温度）。12个线粒体基因组将被完全测序，允许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，将在一个种群间杂种和对照中评估基因表达，以鉴定与性别特异性线粒体-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.