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

线粒体对桡足类 Tigriopus californicus 雄性和雌性健康的影响

• 批准号: 1656048
• 负责人: Suzanne Edmands
• 金额: $ 62.58万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1656048&HistoricalAwards=false
• 关键词: Mitochondrial; effects; male; female; fitness

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.

这个项目测试了一个假设，即对雄性有害的突变可以在基因组的线粒体部分积累，而线粒体只能通过雌性遗传。这些对雄性有害的突变没有被去除，因为自然选择对雄性的影响没有传递给下一代。大多数熟悉的生物体都有一个位于细胞核中的大基因组，它从父母双方遗传而来，另外还有一个位于线粒体中的小基因组。线粒体是每个细胞的电池，它只从母亲那里遗传。线粒体基因产物与核基因产物相互作用，执行关键的生命功能。据预测，对男性有害的突变会在线粒体基因组中积累，并导致其适应性降低。该项目将研究核和线粒体基因组之间的相互作用，以及一种小型海洋贝类——加利福尼亚虎足类——对雄性和雌性健康的影响。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。这一假设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个衰老过程有关。除了研究本身，该项目还将培养一名博士后研究员、博士生和本科生研究员。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的合作（旨在提高公众对进化论的认识），以及与面向初高中学生的大学项目的合作（旨在加强为少数族裔服务的班级的进化论课程）。雄性特异性突变负荷将通过创建12个细胞质杂交种来评估，其中来自12个不同种群的线粒体将通过大约15代回交转移到相同的等基因核背景上。这12个品系将包括11个种群间杂交品种和1个对照品种。12个品系中的每一个品系都将用于测定性别特异性生育能力和全生命周期（180天以上）的存活率。这些数据将用于测试线粒体效应中性别差异的大小，测试性别差异对生育能力的影响是否大于对寿命的影响，以及测试这种性别差异是否会在生命后期和更高的代谢需求（例如更高的温度）下加剧。12个线粒体基因组将被完全测序，从而可以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，基因表达将在一个种群间杂交和对照中进行评估，以确定与性别特异性核分裂冲突相关的核基因。

项目成果

Mitonuclear interactions alter sex-specific longevity in a species without sex chromosomes

• DOI: 10.1098/rspb.2021.1813
• 发表时间: 2021-11-10
• 期刊: PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
• 影响因子: 4.7
• 作者: Flanagan, Ben A.;Li, Ning;Edmands, Suzanne
• 通讯作者: Edmands, Suzanne

Exogenous oxidative stressors elicit differing age and sex effects in Tigriopus californicus

• DOI: 10.1016/j.exger.2022.111871
• 发表时间: 2022-07-02
• 期刊: EXPERIMENTAL GERONTOLOGY
• 影响因子: 3.9
• 作者: Flanagan，Ben A.;Huang，Elaine;Edmands，Suzanne
• 通讯作者: Edmands，Suzanne

Genomic signatures of mitonuclear coevolution across populations of Tigriopus californicus

• DOI: 10.1038/s41559-018-0588-1
• 发表时间: 2018-08-01
• 期刊: NATURE ECOLOGY & EVOLUTION
• 影响因子: 16.8
• 作者: Barreto, Felipe S.;Watson, Eric T.;Burton, Ronald S.
• 通讯作者: Burton, Ronald S.

Sex-specific stress tolerance, proteolysis, and lifespan in the invertebrate Tigriopus californicus

• DOI: 10.1016/j.exger.2019.02.006
• 发表时间: 2019-05-01
• 期刊: EXPERIMENTAL GERONTOLOGY
• 影响因子: 3.9
• 作者: Foley, Helen B.;Sun, Patrick Y.;Edmands, Suzanne
• 通讯作者: Edmands, Suzanne