COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

这项工作的长期目标是理解 观察到的DNA序列变异的不同水平和模式 以及物种之间的差异。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 为了确定自然种群的基因组多样性水平， 尤其是对果蝇来说。研究表明， 全基因组范围内DNA变异水平与 果蝇中的重组和明确的中央 重组格局的知识对于 了解自然种群中的基因组多样性。具体目标 包括分离、定位和估计突变率 黑腹盘藻、拟黑腹盘藻和拟黑腹盘藻的微卫星基因座。 这些微卫星将用于遗传和物理测绘。 研究以确定这些物种的重组景观。 此外，还将对DNA序列和微卫星变异进行分析 在这些物种的自然种群中检查这些物种 变异/重组相关性及其对推论的影响 物种有效种群数量和物种合并时间。测试 一系列解释这种相关性的假设是基于 常染色体和X染色体变异的比较，以及 DNA序列和DNA序列的频率分布分析 微卫星在种群内和种群间的变异。不管 其原因，观察到的相关性表明，有效人口 大小(Ne)对于一个基因组中的所有基因来说并不相同，可以是 极大地降低了物种的有效种群数量 选择性扫描或背景导致的低复合区域 选择。我们将利用NE中的这种区域差异来测试 关于替换的适合性后果的替代假设， 沉默和非编码序列变体。这些类别中的每一类 根据预测，多态的行为与 种内变异与种间变异的相对比例取决于 关于他们是微弱的优势，严格的中性，还是轻微的 有害的。这些研究将使我们更深入地了解 随着时间的推移塑造种群遗传变化的进化力量 和空间，并将提供一个概念框架，在其中解释 来自其他生物和人类的DNA多态数据。

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.