COMPARATIVE BIOLOGY AND GENETICS OF POSTPONED AGING

延迟衰老的比较生物学和遗传学

• 批准号: 3790467
• 负责人: Joseph L. Graves
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3790467
• 关键词: Drosophilidae; aging; alleles; animal breeding; animal population genetics; biomarker; chromosome movement; evolution; fertility; gel electrophoresis; gene frequency; genetic polymorphism; genotype; geographic site; growth media; linkage mapping; longevity; phenotype; physiologic stressor; species difference; superoxide dismutase

The proposed research would employ a diversity of Drosophila species and a diversity of D. melanogaster genetic backgrounds to test evolutionary genetic findings obtained from a few D. melanogaster stocks. Firstly, it is proposed to select for postponed aging in five widely separated species within the Drosophila genus: D. melanogaster, D. simulans, D. pseudoobcura, D. repleta, and D. virilis. Each species would be collected from the wild and then established as an outbred laboratory population. Upon establishment, the species would be assayed for longevity, age- specific fecundity and physiological traits. Selection would be carried out on these populations to create 50 (5 species x 10 lines) new populations of early- and late-reproduced lines. These lines would then be compared both within and between species for patterns of genetic and physiological adaptations associated with selection for postponed aging. This in turn would address the extent to which related species have common genetic mechanisms affecting aging, and thus the extent to which genetic mechanisms that can be used to postpone aging in mice might be general to other mammalian species. Secondly, the proposed research would assemble alternative electrophoretic genotypes by hybridizing electrophoretically homozygous D. melanogaster lines, and then test these genotypes for their effects upon aging. This method involves the creation of inbred lines derived from outbred populations, where these inbred lines are fixed for different electromorphs. These inbred lines can then be crossed in multiple combinations to create hybrid genotypes that (a) possess the desired electrophoretic genotype, (b) are not inbred, and (c) come from different source populations. This allows tests for the effect of electrophoretic alleles upon aging-related characters (longevity, fecundity, stress resistance, and so on) without either inbreeding depression or confounding genetic effects of nearby alleles in accidental linkage disequilibrium, when data from multiple populations are used. The first locus that would be examined in this manner is superoxide dismutase.

拟议的研究将采用多种果蝇物种和 D. melanogaster遗传背景的多样性测试进化 遗传发现是从几个D. melanogaster股票获得的。 首先，它 建议在五个广泛分开的物种中选择推迟衰老 在果蝇属中：D。Melanogaster，D。Simulans，D。 Pseudoobcura，D。Pepleta和D.Virilis。 每个物种将被收集 从野外开始，然后建立为近代实验室人口。 建立后，该物种将被分析以长寿，年龄 - 特定的繁殖力和生理特征。 选择会携带 在这些人群上创建50个（5种x 10行）新的 早期和晚期生产线的种群。 这些线将是 比较物种内部和物种之间的遗传模式和 与选择推迟衰老有关的生理适应性。 反过来，这将解决相关物种具有共同的程度 影响衰老的遗传机制，因此遗传的程度 可用于推断小鼠衰老的机制可能是一般的 其他哺乳动物。 其次，拟议的研究将组装替代电泳 通过杂交电泳纯合的基因型D. melanogaster 线，然后测试这些基因型对衰老的影响。 这 方法涉及创建源自近交的近交系 种群，这些近交系的固定为不同 静电杆。 然后可以将这些近交系列交叉多个 组合创建（a）具有所需的混合基因型 电泳基因型，（b）不是近交，（c）来自不同 来源人群。 这允许测试电泳的影响 等位基因与衰老相关的角色（长寿，繁殖力，压力） 阻力等）没有近亲抑郁或混淆 附近等位基因在意外连锁不平衡中的遗传作用， 当使用来自多个人群的数据时。 第一个基因座 以这种方式检查是超氧化物歧化酶。