Unraveling the Molecular and Population Genetic Complexity of Adaptive Trait Evolution

揭示适应性特征进化的分子和群体遗传复杂性

• 批准号: 10343824
• 负责人: JOHN E POOL
• 金额: $ 32.01万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10343824
• 关键词: Abdomen; African; Alleles; Altitude; Biological Assay; Biological Models; Biology; CRISPR/Cas technology; Candidate Disease Gene; Case Study; Chromosome Mapping; Color; Complement; Complex; Data; Diabetes Mellitus; Disease; Dissection; Drosophila genus; Drosophila melanogaster; Enzymes; Ethiopia; Ethiopian; Evolution; Gene Expression Regulation; Genes; Genetic; Genetic Complementation Test; Genetic Drift; Genetic Epistasis; Genetic Heterogeneity; Genetic Predisposition to Disease; Genetic Variation; Genetic study; Genome; Genomic Segment; Genomics; Goals; Grain; Heart Diseases; Human; Inbreeding; Investigation; Knowledge; Light; Logic; Melanosis; Methods; Modeling; Modernization; Molecular; Molecular Genetics; Mutation; Natural Selections; Nature; Participant; Phenotype; Pigmentation physiologic function; Play; Population; Population Genetics; Prevalence; Process; Property; Quantitative Trait Loci; Recombinants; Recurrence; Research; Research Personnel; Research Project Summaries; Resolution; Resources; Role; System; Testing; Time; Tissues; Transgenic Organisms; UV protection; Variant; Work; causal variant; experimental study; genetic architecture; genetic variant; genome editing; genome wide association study; genomic variation; human disease; improved; insight; novel; personalized genomic medicine; predictive test; response; skills; trait; transcription factor; transcriptome sequencing

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.

项目概要 这项研究旨在比其他研究更深入、更细致地了解适应遗传学。 迄今为止已成为可能。虽然现在已经通过全基因组检测到许多与性状相关的变异 关联研究中，很少有这些 SNP 与适应性表型直接相关，并且 遗传相互作用决定了它们的影响是否对选择可见。这些知识对于 构建现实且可测试的模型来了解群体内遗传变异的广泛程度 通过自然选择的筛子。 高海拔果蝇种群黑色素病的进化提供了几个线索 这项努力的关键优势。首先，该物种提供关键的功能遗传和种群 基因组资源，以及注释良好的基因组。二、先前的分子和进化研究 提供了有关该性状的丰富背景知识，包括一组引人注目的候选基因。第三， 对同一物种种群之间近期适应性进化的研究最大化了遗传的效用 等位基因的绘图、群体遗传学和功能比较。这些功能将允许解剖 以无与伦比的细节对该模型的适应性特征进行了研究，产生了以下方面的见解： 1. 致病变异的功能性质， 2. 适应性反应的遗传变异性， 3. 适应性变异中上位性的普遍性和分子逻辑， 4. 适应性变化中神秘变异的作用， 5. 长期遗传变异在性状进化中的重要性。 这项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中的重要性， 理解包括人类疾病在内的复杂特征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综合的研究计划的支持，该计划利用了研究人员的 互补的背景融合新颖的分子实验、基因组分析和统计推断。 这项研究将鉴定埃塞俄比亚黑腹果蝇黑色素适应背后的遗传变异， 将基因组作图和变异分析与转基因测试相结合，以查明致病变化（目标 1）。它 还将超越这一目标，揭示调节表型影响的复杂相互作用 致病变异（目标 2），检查组织和群体特异性基因调控以及非累加性 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，以澄清 分子和遗传水平上适应性特征进化的复杂性。