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.

项目摘要 这项研究的目的是对适应遗传学的更深入，更细微的理解 已经有可能了。虽然现在已经通过基因组检测到许多与性状相关的变体 关联研究，这些SNP中很少有与适应性表型直接相关的 控制其影响是否可见的遗传相互作用。这样的知识对 组成现实且可检验的模型，以了解种群中常规遗传变异的广泛模型 通过自然选择的筛子进行漏斗。 高海拔果蝇中的黑人主义的演变，可提供几种 这项工作的关键优势。首先，该物种提供关键的功能遗传和人口 基因组资源，以及井井有条的基因组。第二，先前的分子和进化研究 已经提供了有关特征的强大背景知识，包括一组引人注目的候选基因。第三， 对同一物种种群之间的最新适应性演变的研究最大化了遗传的效用 等位基因的映射，种群遗传学和功能比较。这些功能将允许解剖 该模型的自适应特征是无与伦比的细节，产生了有关： 1。因果变体的功能性质， 2。自适应反应的遗传变异性， 3。自适应变体中上毒的患病率和分子逻辑， 4。神秘变化在自适应变化中的作用， 5。在特质进化中静态遗传变异的重要性。 这项研究的结果将提高对自适应进化过程的基本理解。会 还可以告知遗传背景在评估遗传变异的表型影响的重要性，A 了解包括人类疾病在内的复杂性状的遗传结构的关键步骤。调查 这些关键主题将受到一项深刻综合的研究计划的支持，该计划利用研究者的 融合新的分子实验，基因组分析和统计推断的互补背景。 这项研究将确定埃塞俄比亚D. melanogaster中黑色素的基础遗传变异， 将基因组映射和变异分析与转基因测试融合，以查明致病性变化（AIM 1）。它 还将超越该目标，以揭示调节表型影响的复杂互动 致病变异（AIM 2），检查组织和人群特异性基因调节以及非添加性 黑色素变体之间的相互作用。这些调查将提供一项关键的案例研究，以阐明 在分子和遗传水平上自适应性状进化的复杂性。