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 用于测试进化的黑腹果蝇遗传背景的多样性 从一些黑腹果蝇种群中获得的遗传发现。 首先，它 建议选择五个广泛分离的物种来推迟衰老 果蝇属：D. melanogaster、D. simulans、D. 假暗斑 D. repleta 和 D. virilis。 每个物种都会被收集 来自野外，然后建立为远交实验室群体。 建立后，将对该物种进行寿命、年龄分析。 特定的繁殖力和生理特征。 将进行选择 在这些种群上创造 50 个（5 个物种 x 10 个品系）新品种 早期和晚期繁殖系的种群。 这些行将是 比较物种内部和物种之间的遗传模式和 与延迟衰老选择相关的生理适应。 这反过来又将解决相关物种具有共同点的程度 影响衰老的遗传机制，以及遗传影响的程度 可用于推迟小鼠衰老的机制可能普遍用于 其他哺乳动物物种。 其次，拟议的研究将组装替代电泳 通过电泳纯合黑腹果蝇杂交确定基因型 线，然后测试这些基因型对衰老的影响。 这 该方法涉及创建源自远交的近交系 种群，这些自交系针对不同的情况是固定的 电晶型。 然后可以将这些自交系进行多次杂交 组合以创建杂交基因型，该基因型 (a) 具有所需的 电泳基因型，（b）不是近交，（c）来自不同的 来源人群。 这样可以测试电泳的效果 与衰老相关的特征（长寿、生育力、压力）的等位基因 抗性等），没有近交抑制或混杂 意外连锁不平衡中附近等位基因的遗传效应， 当使用来自多个群体的数据时。 第一个位点 以这种方式检查的是超氧化物歧化酶。