CONSEQUENCES OF DELETERIOUS MUTATION

有害突变的后果

• 批准号: 2684830
• 负责人: Michael R LYNCH
• 金额: $ 16.02万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2684830
• 关键词: Branchiopoda; Escherichia coli; animal breeding; animal population genetics; bacterial genetics; biochemical evolution; computer simulation; fertility; gene mutation; genetic models; genetic strain; inbreeding; microorganism culture; microorganism growth; natural selections

DESCRIPTION: Dr. Michael Lynch requests funds for a 5-year project to investigate the nature and consequences of deleterious mutations. The project is comprised of an empirical component and a theoretical component. Empirical studies are proposed to determine the nature and rate of accumulation of mutations in Daphnia and Escherichia coli. Theoretical analyses of the effects of deleterious mutations on extinction rates will be conducted through computer simulation. The accumulation of spontaneous mutations will be monitored in lines derived from natural populations of Daphnia and maintained as clones. Inbred D. pulex and D. pulicaria lines will be generated by inducing sexual reproduction and self-fertilization through 15 generations, and four clonal replicates will be generated from each line. In order to permit the accumulation of mutations without selective elimination, each culture will be maintained by transferring a single randomly chosen offspring to produce the next generation. Fitness, defined as survival and reproduction through six clutches, will be assayed at 10-generation intervals. The rate of change in fitness and the variance in fitness among lines will be estimated. The nature and effects of the mutations that accumulate will be characterized. Aspects to be analyzed include environmental sensitivity, dominance, epistasis, and magnitude of deleterious effects. Estimates obtained from Dr. Lynch's "four-equation" method using clones derived directly from natural populations will be compared to comparable estimates obtained from the mutation-accumulation experiments. A second empirical study will continue and expand on-going mutation- accumulation experiments using E. coli. All lines will be passed through a single-cell bottleneck each generation, with representative cells frozen every 25 cycles. Various growth characteristics of each line relative to representatives of the line in the initial cycle will be assayed. Aspects of the accumulated mutations that will be estimated include the distribution of effects on growth parameters, sensitivity to environmental conditions, and epistasis. The experiment will be repeated using growth-inhibiting and growth-enhancing environments in order to explore the effects of stress on the rate of generation and nature of mutations. Another extension involves monitoring strains carrying known deficiencies in repair pathways. Numerical simulations will be conducted to characterize the effects of deleterious mutations on extinction rates under various breeding systems including random mating, obligate asexuality, and obligate self- fertilization. Mutational effects will be allowed to vary according to a specified distribution, which may include beneficial as well as deleterious mutations. The effects of the nature of epistasis (positively or negatively synergistic) on the rate of accumulation will be addressed. Mutations affecting fertility as well as viability will be studied. The effects on extinction rates of variation in population size and reproductive rate due to environmental factors as well as mutations will be explored.

描述：迈克尔·林奇博士请求为一个为期5年的项目提供资金 调查有害突变的性质和后果。这个 项目由经验部分和理论部分组成 组件。建议进行实证研究，以确定性质和 突变在水蚤和大肠杆菌中累积的速率。 有害突变对人体健康影响的理论分析 消光率将通过计算机模拟进行。 将对自发突变的积累进行连续监测 源自水蚤的自然种群，并以克隆的形式保存。 通过诱导诱变，将产生近交系普氏杜鹃和杜氏杜鹃。 经过15代的有性繁殖和自交，以及 每一株系将产生四个克隆复制。为了 允许在没有选择性消除的情况下积累突变，每个 文化将通过转移一个随机选择的单一 后代生育下一代。健康，定义为生存 并通过六窝繁殖，将在10代时进行测试 间隔时间。适合度的变化率和适合度的变化 行数将会被估计。突变的性质和影响 这一积累将被描述为特征。要分析的方面包括 环境敏感性、优势、上位性和大小 有害的影响。从林奇博士的“四方程式”中获得的估计 使用直接来自自然种群的克隆的方法将是 与通过突变-积累获得的可比估计进行比较 实验。 第二项实证研究将继续并扩大正在进行的突变- 利用大肠杆菌进行的蓄积实验。所有线路都将通过 通过每一代的单细胞瓶颈，具有代表性 细胞每25个周期冷冻一次。每个品种的不同生长特征 线条代表的线条在初始周期中将 接受化验。将被估计的累积突变的各个方面 包括分布对生长参数、灵敏度的影响 与环境条件和上位性有关。这项实验将是 重复使用抑制生长和促进生长的环境 目的：探讨应激对产卵率和产卵率的影响。 突变的本质。另一项扩展涉及监测菌株 在修复途径上带有已知的缺陷。 将进行数值模拟，以表征 不同繁育制度下有害突变对物种灭绝率的影响 包括随机交配、专性无性和专性自我 受精。突变效果将被允许根据 指定的分配，其中可能包括受益分配以及 有害的突变。上位性的影响 (正面或负面协同作用)对累积速度的影响 被称呼为。影响生育能力和生存能力的突变将 被研究。种群变异对物种灭绝率的影响 大小和繁殖率由环境因素和 我们将探索突变。