Unraveling the Molecular and Population Genetic Complexity of Adaptive Trait Evolution

项目摘要 这项研究的目的是为了更深入和更细致的了解适应遗传学，而不是 是可能的。虽然现在已经通过全基因组检测到了许多与性状相关的变异， 关联研究中，这些SNP中很少有直接与适应性表型相关， 基因间的相互作用决定了它们的影响是否对选择是可见的。这些知识对于 构建现实的和可测试的模型，以了解种群内的遗传变异有多普遍 通过自然选择的筛子。 高海拔果蝇种群黑化的进化提供了几个 这一奋进的关键优势。首先，该物种提供了关键的功能遗传和人口 基因组资源，沿着注释良好的基因组。第二，先前的分子和进化研究 已经提供了关于该性状的强有力的背景知识，包括一组引人注目的候选基因。第三、 对同一物种种群之间最近适应性进化的研究， 作图、群体遗传学和等位基因的功能比较。这些特征将允许解剖 该模型的自适应特性的无与伦比的细节，产生的见解： 1.使役变体的功能性质， 2.适应性反应的遗传变异性， 3.适应性变异中上位性的流行和分子逻辑， 4.隐性变异在适应性变化中的作用， 5.持续遗传变异在性状进化中的重要性。 本研究的结果将促进对适应性进化过程的基本理解。它将 还告知遗传背景在评估遗传变异的表型影响方面的重要性， 理解包括人类疾病在内的复杂性状的遗传结构的关键一步。调查 这些关键主题将得到一个深刻的综合研究计划的支持，该计划利用了研究人员的 互补的背景融合新的分子实验，基因组分析和统计推断。 这项研究将确定遗传变异的基础黑适应埃塞俄比亚D。黑腹动物， 融合基因组定位和变异分析与转基因检测，以查明致病变化（目标1）。它 也将超越这一目标，揭示调节表型影响的复杂相互作用， 致病变异（目标2），检查组织和人群特异性基因调控， 黑色素变体之间的相互作用。这些调查将提供一个关键的案例研究，将澄清 在分子和遗传水平上适应性性状进化的复杂性。

Project Summary This research aims for a deeper and more nuanced understanding of the genetics of adaptation than has been possible to date. While many trait-associated variants have now been detected by genome-wide association studies, very few of these SNPs have been directly connected to adaptive phenotypes, and the genetic interactions that govern whether their effects are visible to selection. Such knowledge is crucial to composing realistic and testable models for how widespread standing genetic variation within populations is funneled through the sieve of natural selection. The evolution of melanism in high altitude Drosophila melanogaster populations offers several critical advantages for this endeavor. First, the species offers key functional genetic and population genomic resources, along with a well-annotated genome. Second, prior molecular and evolutionary studies have provided strong background knowledge on the trait, including a compelling set of candidate genes. Third, the study of recent adaptive evolution between populations of the same species maximizes the utility of genetic mapping, population genetics, and functional comparisons of alleles. These features will allow the dissection of this model adaptive trait in unparalleled detail, yielding insights regarding: 1. the functional nature of causative variants, 2. genetic variability of the adaptive response, 3. the prevalence and molecular logic of epistasis among adaptive variants, 4. roles of cryptic variation in adaptive change, 5. the importance of standing genetic variation in trait evolution. Results of this research will advance basic understanding of the adaptive evolutionary process. It will also inform on the importance of genetic background in assessing the phenotypic impact of genetic variants, a key step in understanding the genetic architecture of complex traits including human disease. Investigation of these critical topics will be bolstered by a profoundly integrative research plan that leverages the investigators' complementary backgrounds to fuse novel molecular experiments, genomic analysis, and statistical inference. This research will identify genetic variants underlying melanic adaptation in Ethiopian D. melanogaster, fusing genomic mapping and variation analysis with transgenic tests to pinpoint causative changes (Aim 1). It will also advance beyond that goal to reveal the complex interactions that modulate the phenotypic impact of causative variants (Aim 2), examining tissue- and population-specific gene regulation, and non-additive interactions among melanic variants. These investigations will provide a critical case study that will clarify the complexity of adaptive trait evolution at molecular and genetic levels.