COMPARATIVE MOLECULAR POPULATION GENETICS OF DROSOPHILA

描述(由申请人提供)：我们的长期目标是了解物种内和物种之间不同水平的DNA序列多态的生物学意义和进化意义。特别令人感兴趣的是具有功能后果的变异的频率和性质，这些变异是适应性进化的目标。我们感兴趣的是塑造特定基因的进化力量，以及全基因组变异模式和分子进化的决定因素，因为它们受到重组率变化的影响。我们建议完成单基因和多基因分析，旨在推断作用于同义、非同义和内含子序列变体的选择效应在果蝇和拟果蝇之间的分布。将产生序列多态数据，以检验关于作用于不同类别的序列变体的选择的有效性和方向的假设。我们的主要关注点也将转移到基于微卫星的基因组扫描的扩展上，以进行适应性固定，重点放在黑腹毛虫和拟毛虫X染色体上的2Mb高重组区域。选择性扫描的证据将得到验证，这些选择性扫描的目标将使用更高分辨率的DNA序列多态扫描定位在基因组内。这些数据将允许估计选择的时机、强度和目标。最后，我们将在已确定的选择目标上对基因和相关变异进行分子表征。我们提出的研究将对我们理解基因组进化和生物体适应环境的过程做出重大贡献。它还将有助于基因注释工作，继续作为新的理论研究和统计测试的经验动机，并将提供一个概念框架，用于解释越来越多地从包括人类在内的其他生物获得的DNA多态数据。

DESCRIPTION (provided by applicant): Our long-term goal is to understand the biological significance and evolutionary implications of contrasting levels of DNA sequence polymorphism within and between species. Of particular interest are the frequency and nature of variants with functional consequences that are the targets of adaptive evolution. We are interested in the evolutionary forces shaping specific genes, and in the determinants of genome-wide patterns of variation and molecular evolution as they are influenced by variation in rates of recombination. We propose completing single and multi-gene analyses aimed at inferring the distribution of selective effects acting on synonymous, non-synonymous, and intron sequence variants within and between Drosophila melanogaster and D. simulans. Sequence polymorphism data will be generated in order to test hypotheses concerning the efficacy and direction of selection acting on different classes of sequence variants. Our primary focus will also shift to an extension of our microsatellite-based genome scan for adaptive fixations, focusing on a 2 Mb high-recombination region on the X chromosome of D. melanogaster and D. simulans. Evidence for selective sweeps will be verified and the targets of these selective sweeps localized within the genome using a finer resolution, DNA sequence polymorphism scan. These data will allow estimation of the timing, strength, and target of selection. Finally, we will carry out a molecular characterization of the genes and associated variation at identified targets of selection. Our proposed research will make significant contributions to our understanding of the processes by which genomes evolve and organisms adapt to their environments. It will also contribute to gene annotation efforts, continue to serve as empirical motivation for new theoretical studies and statistical tests, and will provide a conceptual framework in which to interpret DNA polymorphism data increasingly available from other organisms including humans.