COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

了解不同层次和模式的重要性 自然种群DNA序列变异的组织 是理解基因组进化的核心。我们的建议 实验的动机是我们发现了强烈对比的 DNA限制性内切酶切点和蛋白质多态的水平 黑腹多食线虫和拟态多食线虫，显著连锁 3号染色体上多达10个图谱单位的不平衡。 黑素基因及其在染色体和物种间的相关性 在强连锁不平衡和多态倒置之间， 并通过发展中性分子的统计检验 基于种内DNA序列比较的进化 种间差异的变异。我们会得到准确的 种内和种间DNA序列变异的估计。 Blackogaster和D.Simans检验假说来解释 观察到的这些物种内部和之间的变异模式。 这包括玫瑰花的4刀限制酶切点分析， 1(3)这些物种种群样本中的S12和蛇基因， 以及对每个等位基因的随机样本进行直接测序 1(3)S12和玫瑰色基因的物种。我们还将定义 连锁性不平衡的水平和物理极限 第三和第二个基因定位的序列变异 黑腹盘藻和拟盘尾轮虫的染色体研究 连锁不平衡与区域特殊性的关系 重组率的变化(包括由于 存在多态倒置)。这将涉及到得分 用四刀和聚合酶链式反应扩增多态DNA变异体 按经验确定的速率的间隔进行排序 重组是可用的，检查连接的模式 内部和之间的不平衡和序列可变性 倒位染色体，以及染色体倒位比率的测定 倒位杂合子中的重组，看看他们是否 与观察到的连锁不平衡一致，或者是否有些 需要调用选择的形式。

Knowledge of the significance of the diverse levels and patterns of organization of DNA sequence variation in natural populations is central to understanding genome evolution. Our proposed experiments are motivated by our finding of strongly contrasting levels of DNA restriction site and protein polymorphism between Dorscophila melanogaster and D. simulans, significant linkage disequilibrium over as much as 10 map units on chromosome 3 of D. melanogaster and a correlation across chromosomes and species between strong linkage disequilibrium and polymorphic inversions, and by the development of a statistical test of neutral molecular evolution based on the comparison on intra-specific DNA sequence variation with inter-specific divergence. We will obtain accurate estimates of intra-and interspecific DNA sequence variation in D. melanogaster and D. simulans to examine hypotheses to explain the patterns of variation observed within and between these species. This includes a 4-cutter restriction site analysis of the rosy, 1(3)S12 and snake genes in populations samples of these species, and the direct sequencing of a random sample of alleles from each species for the 1(3)S12 and rosy genes. We will also define the levels and physical limits of linkage disequilibrium among genetically mapped sequence variants on the third and second chromosomes of D. melanogaster and D. simulans to examine the relationship between linkage disequilibrium and region-specific variation in rates of recombination (including that due to the presence of polymorphic inversions). This will involve scoring polymorphic DNA variants using 4-cutters and PCR amplification sequencing at intervals for which empirically determined rates of recombination are available, examining patterns of linkage of disequilibrium and sequence variability within and between inversion chromosomes, and the determination of rates of recombination in inversion heterozygotes to see if they are compatible with the linkage disequilibrium observed or whether some form of selection need be invoked.