Comparative Molecular Population Genetics of Drosophila

我们的目标是估计核苷酸变异的频率、位置和功能意义 果蝇基因组中潜在的适应“足迹”。建议数 研究建立在我们成功的初始扫描基础上，使用分散的微卫星基因座的变异 揭示了在X染色体的一个区域预测的六个选择目标。本地化 对其中三个区域的重新测序发现了影响同义词的正选择 位点(在Notch)，氨基酸序列多样化(在CG18508)和两次选择性扫描 推测与转录因子结合位点有关。我们的初步分析还显示， 需要更完整、更高质量的序列覆盖，以具有统计能力来区分 从非均衡人口结构中进行选择，并对选择对象进行精确定位。我们会 使用新开发的选择足迹统计测试来公开分析最近 已发布(www.dpgp.org，Langley Pers。通信。)对39个大麦自交系进行了全序列测定。 产于北美的黑猩猩。我们还将对50行的非洲样本进行重新排序 2 Mb区域的X染色体，以估计时间，强度和靶点 在这两个地理和生态不同的种群中进行选择。我们将进行化验 来自中国的22个额外总体样本中假定目标周围的序列变异 以定义发生扫掠的地理区域。这些数据将 提供对选择性活动的生态/地理背景的洞察。最后，我们会 从功能上描述三个已确定的选择目标。我们将检验以下假设 与Notch异常同义位点进化相关的翻译调控 组织培养和生殖系转化转录检测。我们将测试主持人的角色- CG18508的防御和/或局部天然免疫功能，并评估功能 选择性固定尾部转录因子结合位点差异的后果 CG18508上游的种群。我们的结果为理解 果蝇适应的频率和分子基础，提供了一个基准 来检验我们关于其他基因组适应性进化的假设。

Our goal is to estimate the frequency, location, and functional significance of nucleotide variation underlying "footprints" of adaptation in the Drosophila melanogaster genome. The proposed research builds on our successful initial scan using variation at dispersed microsatellite loci that revealed six predicted targets of selection in one region of the X-chromosome. Localized resequencing of three of these regions has uncovered positive selection affecting synonymous sites (at Notch), amino acid sequence diversification (at CG18508) and two selective sweeps putatively associated with transcription factor binding sites. Our initial analyses also revealed the need for more complete, high-quality sequence coverage to have statistical power to distinguish selection from non-equilibrium demography and to precisely localize targets of selection. We will use newly developed statistical tests for footprints of selection to analyze recently publically released (www.dpgp.org, Langley pers. Comm.) complete re-sequencing of 39 inbred lines of D. melanogaster from North American. We will also re-sequence an African sample of 50 lines for a 2 Mb region of the X-chromosome in order to estimate the timing, strength, and targets of selection in these two geographically and ecologically distinct populations. We will assay sequence variation around putative targets in twenty-two additional population samples from around the world to define the geographic regions in which the sweeps occurred. These data will provide insight into the ecological/geographic context of the selective event. Finally, we will functionally characterize three identified targets of selection. We will test hypotheses of translational regulation associated with unusual synonymous site evolution at Notch using both tissue culture and germline transformation transcription assays. We will test for a role in host- defense and/or local innate immune function at CG18508, and evaluate the functional consequences of selectively fixed Caudal transcription factor binding site difference between populations upstream of CG18508. Our results lay the foundation for understanding the frequency and molecular basis of adaptation in Drosophila, providing a benchmark against which to test our assumptions about adaptive evolution in other genomes.