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: 9901541
• 负责人: JOHN E POOL
• 金额: $ 32.39万
• 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 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901541
• 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 这项研究旨在更深入、更细微地理解适应的遗传学，而不是 到目前为止都是可能的。虽然现在已经在全基因组范围内检测到了许多与性状相关的变异 关联研究表明，这些SNP中很少有与适应性表型直接相关的，而且 基因交互作用决定了它们的影响对选择是否可见。这样的知识对于 构建真实和可测试的模型，以了解种群内长期遗传变异的广泛性 穿过了自然选择的筛子。 在高海拔果蝇种群中黑化的进化提供了几个 这一努力的关键优势。首先，该物种提供了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。第二，先前的分子和进化研究 提供了关于该性状的强大背景知识，包括一组令人信服的候选基因。第三, 对同一物种种群间最近适应性进化的研究最大限度地利用了遗传 作图、群体遗传学和等位基因的功能比较。这些功能将允许解剖 这一模型的适应性特征的无与伦比的细节，产生了关于以下方面的见解： 1.致因变体的功能性质， 2.适应性反应的遗传可变性， 3.适应变异体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.保持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。会的 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，a 了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深度整合的研究计划的支持，该计划利用调查人员的 互补背景，融合新颖的分子实验、基因组分析和统计推断。 这项研究将确定埃塞俄比亚黑腹鼠黑色适应的遗传变异， 将基因组图谱和变异分析与转基因测试相结合，以确定引起变化的原因(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 致病变异体(目标2)，检查组织和群体特有的基因调控，以及非加性 黑色变种之间的相互作用。这些调查将提供一个关键的案例研究，将澄清 分子和遗传水平上适应性性状进化的复杂性。