COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

关于大多数突变是否导致 天然存在的多态性是中性的，轻微有害的，或 优势的平均选择中这些看似细微的差异 系数对我们关于哪些过程的世界观有重大影响 推动分子进化提出的许多实验来自 发现DNA水平之间存在显着的正相关性， 限制性位点多态性和区域重组率 果蝇不同选择效应的突变是 预测在高与低的区域表现不同 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， 在D. melanogaster和D. 模拟。所获得的数据将提供新的见解， 在水平和分布的重组率的差异， DNA变异，并将允许测试替代假设，以解释 对于DNA变异水平之间的一般相关性， 重组率X连锁非编码位点变异的比较 与第三个染色体基因将允许歧视的相对 “选择性扫描”的贡献与固定的 有利的突变相对于“背景选择”， 消除有害的突变。所得结果之间的对比 在津巴布韦和马里兰州， 这是伴随着D.黑腹菌的 假设区域水平的连锁不平衡是一个简单的 将测试区域重组率的功能。缺乏 这种关系表明上位选择作用很强。的 还将检查新突变的选择性效应的分布 通过比较内的多态性水平和之间的差异， D. simulans和D.黑腹菌三个基因的相对速率检验 高重组率，使用D.雅库巴作为外群体，将提供一个 框架，以测试突变率和有效性的差异， 人口规模，以及选择效果之间的差异 替换、同义和非编码变异。水平和 多态性的分布将提供额外的区分， 群体大小和突变率的差异。的重要性 群体遗传学方法来解决这些问题是，它提供了 信息的历史水平的选择，而不仅仅是那些在 礼物了解影响遗传变化的力量， 人口在时间和空间上的变化对于更深入地理解 人类遗传疾病的动力学， 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.