COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

这项工作的长期目标是了解 不同水平和模式的DNA序列变异中观察到的 和物种之间。 实验和理论工作已经开始， 揭示自然选择和遗传连锁相互作用的方式 为了确定自然种群中基因组多样性的水平， 尤其是果蝇。 研究表明， DNA变异水平与基因组DNA变异率之间的相关性 在果蝇中的重组，并明确了中央 重组景观知识的重要性， 了解自然种群的基因组多样性。 具体目标 包括分离、定位和估计突变率， 在黑腹果蝇、拟黑腹果蝇和拟暗腹果蝇中发现了微卫星位点。 这些微型卫星将用于遗传和物理绘图 研究来确定这些物种的重组景观。 此外，还将分析DNA序列和微卫星变异 在这些物种的自然种群中， 变异/重组的相关性和推论的含义 物种有效种群大小和物种聚结时间。 测试 提出了解释相关性的假设， 常染色体和X染色体上的变异比较， DNA序列的频率分布分析， 群体内和群体间的微卫星变异。 无论 其原因，观察到的相关性表明，有效人口 大小（Ne）对于基因组中的所有基因是不相同的，并且可以是不同的。 大大减少到物种有效种群规模以下， 由于选择性扫描或背景而导致的低复合区域 选择. 我们将利用Ne的这种区域变化来检验 关于替代的适应性后果的替代假设， 沉默和非编码序列变体。 上述各类 多态性被预测为关于 种内与种间变异的相对比例取决于 他们是否是弱有利的，严格中立的，还是轻微的， 有害的 这些研究将使人们更深入地了解 随着时间的推移， 并将提供一个概念框架来解释 来自其他生物和人类的DNA多态性数据。

The long term goal of this work is to understand the significance of the diverse levels and patterns of DNA sequence variation observed within and between species. Experimental and theoretical work has begun to reveal the ways in which natural selection and genetic linkage interact to determine levels of genomic diversity in natural populations, particularly for Drosophila. Studies have demonstrated a positive genome-wide correlation between levels of DNA variation and rates of recombination in Drosophila melanogaster and have made clear the central importance of the knowledge of the recombinational landscape for understanding genomic diversity in natural populations. Specific aims include the isolation, localization and estimation of mutation rates for microsatellite loci in D.melanogaster, D.simulans and D.pseudoobscura. These microsatellites will be used in both genetic and physical mapping studies to determine the recombinational landscapes for these species. In addition, DNA sequence and microsatellite variation will be assayed in natural populations of these species to examine the generality of the variation/recombination correlation and implications for inferences of species effective population size and species coalescent times. Tests of hypotheses to explain the correlation are proposed based on comparisons of variation on autosomes and X-chromosomes, and the analyses of the frequency distribution of DNA sequence and microsatellite variation within and between populations. Regardless of its cause, the observed correlation indicates that effective population size (Ne) is not the same for all genes across a genome, and can be dramatically reduced below the species effective population size in regions of low recombination due to selective sweeps or background selection. We will exploit this regional variation in Ne to test alternative hypotheses as to the fitness consequences of replacement, silent and noncoding sequence variants. Each of these classes of polymorphism is predicted to behave differently with regard to the relative proportion of variation within versus between species depending on whether they are weakly advantageous, strictly neutral, or slightly deleterious. These studies will provide a deeper understanding of the evolutionary forces that shape genetic change in populations over time and space and will provide a conceptual framework in which to interpret DNA polymorphism data from other organisms and humans.