COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

关于大多数突变是否会导致 自然发生的多态是中性的，稍微有害的，或者 有利的。这些看似细微的平均选择差异 系数对我们关于什么过程的世界观有重大影响 推动分子进化。许多提出的实验都是从 发现DNA水平之间存在显著的正相关 限制性内切酶切点多态与区域重组率 黑腹果蝇。具有不同选择效应的突变有 预计在高海拔地区和低海拔地区表现不同 重组。这些不同的行为被用来检验假设 关于自然选择效应的相对分布 黑腹毛虫和黑腹毛虫自然种群发生变异。 人形动物。获得的数据将为我们提供新的视角来了解 重组速度在水平和分布上的差异 DNA变异，并将允许对替代假设的测试 对于DNA变异水平和 重组率。X连锁非编码区变异的比较 对第三条染色体的基因将允许对亲属的歧视 与固定有关的“选择性扫视”的贡献 与“背景选择”相关的有利突变 消除有害的突变。获得的结果之间的对比 在津巴布韦和马里兰州可能会提供对选择水平的洞察 这伴随着D.Blackogaster建立温带地区。这个 假设区域联系不平衡的水平是一个简单的 将测试区域重组率的函数。缺乏 这种关系将意味着强烈的上位性选择。这个 还将检查新突变的选择效应的分布情况。 通过比较基因内的多态水平和基因之间的差异 D.Simans和D.Blackogaster。三个基因的相对比率检验 使用D.Yakuba作为外群的高重组率将提供 用于测试突变率和有效性差异的框架 种群大小，以及不同种群之间选择效应的差异 替换、同义和非编码变体。水平和 多态的分布将提供额外的歧视 种群大小和突变率的差异。重要的是一个 对这些问题的群体遗传学方法是它提供了 有关历史层级的选择的信息，而不仅仅是那些在 现在时。了解影响基因变化的因素 人口随时间和空间的变化是加深理解的基础 人类遗传病的动力学和对为什么 我们的基因组是可变的。

There is considerable debate over whether most mutations leading to naturally occurring polymorphisms are neutral, slightly deleterious, or advantageous. These seemingly subtle differences in average selection coefficient have a major impact on our world view about what processes drive molecular evolution. Many of the experiments proposed follow from the finding of a significant positive correlation between levels of DNA restriction site polymorphism and the regional rate of recombination in Drosophila melanogaster. Mutations of different selective effects are predicted to behave differently in regions of high versus low recombination. These different behaviors are used to test hypotheses concerning the relative distribution of selective effects of naturally occurring variation in natural populations of D. melanogaster and D. simulans. The data obtained will provide new insight into the impact of differences in the rate of recombination on the level and distribution of DNA variation, and will allow tests of alternative hypotheses to account for the general correlation between levels of DNA variation and recombination rates. Comparison of noncoding site variation at X-linked vs. third chromosomal genes will allow discrimination of the relative contributions of "selective sweeps" associated with the fixation of advantageous mutations versus "background selection" associated with the elimination of deleterious mutations. Contrasts between results obtained in Zimbabwe and Maryland may provide insight into the level of selection that accompanied the founding of temperate regions by D. melanogaster. The hypothesis that regional levels of linkage disequilibrium are a simple function of regional rates of recombination will be tested. The lack of such a relationship would suggest strong epistatic selection. The distribution of selective effects of new mutations will also be examined by comparison of levels of polymorphism within and differentiation between D. simulans and D. melanogaster. Relative rate tests of three genes with high recombination rates, using D. yakuba as the outgroup, will provide a framework in which to test for differences in mutation rate and effective population size, as well as differences in selective effects between replacement, synonymous and noncoding variation. The level and distribution of polymorphism will provide additional discrimination of population size and mutation rate differences. The importance of a population genetic approach to these questions is that it provides information on historical levels of selection, not simply those acting at present. Understanding the forces that influence genetic change in populations over time and space is fundamental to a deeper understanding of the dynamics of human genetic disease and to an understanding of why our genome is variable.