Comparative Molecular Population Genetics of Drosophila

果蝇的比较分子群体遗传学

• 批准号: 7587713
• 负责人: CHARLES F AQUADRO
• 金额: $ 32.66万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7587713
• 关键词: Affect; African; American; Amino Acid Sequence; Benchmarking; Binding Sites; Biological; Biological Assay; Biological Process; Codon Nucleotides; Conflict (Psychology); Coupled; DNA Resequencing; DNA Sequence; Data; Data Set; Demography; Drosophila genus; Drosophila melanogaster; Environment; Equilibrium; Evaluation; Event; Evolution; Foundations; Frequencies; Gene Frequency; Genes; Genetic Transcription; Genome; Geographic Locations; Goals; Host Defense; Human; Link; Location; Mediating; Microsatellite Repeats; Modeling; Molecular; Natural Immunity; Natural Selections; Nucleotides; Organism; Population; Population Genetics; Research; Role; Sampling; Scanning; Site; Testing; Time; Translational Regulation; Validation; Variant; Work; X Chromosome; base; comparative; follow-up; immune function; insight; notch protein; pathogen; sample fixation; simulation; success; tissue culture; transcription factor; translation assay

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.

我们的目标是估计核苷酸变异的频率、位置和功能意义 果蝇基因组中适应的潜在“足迹”。拟议的 研究建立在我们成功的初步扫描基础上，利用分散的微卫星位点的变异 揭示了 X 染色体某一区域的 6 个预测选择目标。本地化 对其中三个区域的重新测序发现了影响同义的正选择 位点（Notch）、氨基酸序列多样化（CG18508）和两次选择性扫描 推测与转录因子结合位点相关。我们的初步分析还揭示了 需要更完整、高质量的序列覆盖，以具有统计能力来区分 从非均衡人口统计中进行选择，并精确定位选择目标。我们将 使用新开发的统计测试对选择的足迹进行最近的公开分析 发布了（www.dpgp.org，Langley pers. Comm.）39 个 D. 近交系的完整重测序。 来自北美的黑腹果蝇。我们还将对 50 个品系的非洲样本进行重新测序 X 染色体的 2 Mb 区域，以估计 X 染色体的时间、强度和目标 对这两个地理和生态上不同的种群进行选择。我们将化验 来自另外 22 个群体样本中假定目标的序列变异 世界各地以确定发生扫描的地理区域。这些数据将 提供对选择性事件的生态/地理背景的洞察。最后，我们将 功能上描述了三个确定的选择目标。我们将测试以下假设 与 Notch 异常同义位点进化相关的翻译调控 组织培养和种系转化转录测定。我们将测试主机中的角色- CG18508 的防御和/或局部先天免疫功能，并评估功能 选择性固定尾端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 测试我们关于其他基因组适应性进化的假设。