COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

了解不同层次和模式的重要性 自然种群中DNA序列变异的组织 是理解基因组进化的核心 我们提出的 实验的动机是我们发现的强烈对比 DNA限制性位点和蛋白质多态性水平之间 Dorscophila melanogaster和D. simulans，重大联系 在D. 3号染色体上的不平衡可达10个图位单位。 黑腹鱼与染色体和物种之间的相关性 强连锁不平衡和多态倒位之间的关系， 通过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。 我们将获得准确的 D.种内和种间DNA序列变异估计 melanogaster和D. simulans检验假设来解释 在这些物种内部和之间观察到的变化模式。 这包括对玫瑰的4-切割酶限制性位点分析， 1（3）S12和蛇基因在这些物种的群体样品， 并对来自每个人的等位基因的随机样本进行直接测序， 1（3）S12和rosy基因。 我们还将定义 连锁不平衡的水平和物理界限 第三和第二基因组上的基因图谱序列变异 D. melanogaster和D. simulans检查 连锁不平衡与区域特异性的关系 重组率的变化（包括由于 多态倒位的存在）。 这将涉及得分 使用4-切割器和PCR扩增的多态性DNA变体 在根据经验确定的 重组是可用的，检查连锁模式， 内部和之间的不平衡和序列变异性 倒位染色体，以及确定 倒位杂合子中的重组，看看它们是否 与观察到的连锁不平衡相一致，或者一些 需要进行选择。

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.