Genomic Diversity and the Architectures of Adaptation and Incompatibility

基因组多样性以及适应和不相容的架构

• 批准号: 10593052
• 负责人: JOHN E POOL
• 金额: $ 38.03万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593052
• 关键词: Address; African; Architecture; Disease; Drosophila genus; European; Evolution; Future; Generations; Genes; Genetic; Genetic Drift; Genetic Epistasis; Genetic Variation; Genetic study; Genome; Genomics; Heart Diseases; Immune; Individual; Infertility; Maps; Medical; Natural Selections; Penetrance; Performance; Population; Portraits; Process; Reproduction; Research; Role; Shapes; Signal Transduction; Spontaneous abortion; System; Transgenic Organisms; Variant; Work; computer studies; cost effective; diabetes risk; disorder risk; experimental study; genetic architecture; genetic resource; genetic variant; genome annotation; genomic data; human disease; insect disease vector; novel strategies; programs; reproductive; scale up; tool; trait

Project Summary: Genomic Diversity and the Architectures of Adaptation and Incompatibility This research program addresses fundamental yet unresolved questions at the interface between genetic variation and evolutionary processes. In particular, it focuses on three interconnected research themes: (1) The Genetic Complexity of Adaptive Trait Evolution, (2) The Genetic Basis of Early Stage Reproductive Isolation, and (3) The Determinants of Genomic Diversity and Adaptive Potential. It fuses ambitious but cost-effective Drosophila experiments with novel approaches to the analysis of large genomic data sets. D. melanogaster offers critical advantages for this work. The global expansion of this species enables the study of adaptive trait differences, and partial reproductive isolation, between populations that diverged in the last ~10,000 years. Due to this recent time-scale, adaptive differences may be detected from genetic variation. The experimental efficiency of Drosophila allows the study of large lab populations across many generations. Its compact genome allows economical sequencing. Once relevant genes are found, functional confirmation and study are aided by a well-annotated genome and a wealth of genetic resources and transgenic tools. This research will bolster understanding of The Genetic Complexity of Adaptive Trait Evolution. Initial findings have suggested a portrait of adaptation that often begins with standing genetic variation, includes variants with larger effect sizes, and features variable genetic architectures among individuals. Proposed work will solidify and extend these inferences in multiple respects, including by launching scaled-up mapping studies for a wider range of adaptive traits, and pursuing previous hints of epistasis involving adaptive variants. Proposed work will also open up a promising new system for studying The Genetic Basis of Early Stage Reproductive Isolation. African and European D. melanogaster show evidence of incompatibilities impacting viability and reproduction, but these have received no genetic study. This research will deploy a combination of incompatibility mapping and population genomics to identify specific incompatibility genes for further study, and it will advance understanding of the genetic architecture of the earliest stages of reproductive isolation. Finally, this research will clarify The Determinants of Genomic Diversity and Adaptive Potential. This work will feature experimental and computational studies on the relative roles of neutral and adaptive genetic diversity in future adaptation, and the most relevant ways to quantify each. It will also investigate the relative importance of different types of natural selection in shaping genomic diversity, including by probing the utility of genetic differentiation between populations to separate the signals of positive and negative selection. Collectively, this research is highly consequential for basic evolutionary genetics. It also holds strong medical relevance in terms of the relevance of local adaptation and epistasis for the genetic basis of human disease and infertility, and for understanding the evolutionary dynamics of insect disease vectors.

项目摘要：基因组多样性以及适应性和不相容性的体系结构 该研究计划在遗传之间解决了基本但尚未解决的问题 变化和进化过程。特别是，它侧重于三个相互联系的研究主题：（1） 自适应性状进化的遗传复杂性，（2）早期生殖的遗传基础 分离，（3）基因组多样性和适应潜力的决定因素。它融合了雄心勃勃，但 具有成本效益的果蝇实验，采用了大型基因组数据集分析的新方法。 D. Melanogaster为这项工作提供了关键的优势。该物种的全球扩展使 研究自适应性状差异和部分生殖分离的研究 最后〜10，000年。由于最近的时间尺度，可以从遗传变异中检测到自适应差异。 果蝇的实验效率允许在许多世代研究大型实验室人群。 它的紧凑基因组允许经济测序。一旦找到相关基因，功能确认 和研究得到了良好的基因组以及大量遗传资源和转基因工具的帮助。 这项研究将增强对自适应性状进化的遗传复杂性的理解。最初的 调查结果提出了适应的肖像，通常始于立遗传变异，包括 具有较大效果大小的变体，并且具有个体之间的遗传体系结构。建议的工作 将在多个方面巩固和扩展这些推论，包括通过启动扩展映射研究 对于更广泛的自适应特征，并追求了涉及自适应变体的上学提示。 拟议的工作还将为研究早期的遗传基础开放一个有希望的新系统 生殖隔离。非洲和欧洲D. Melanogaster显示出影响不兼容的证据 生存力和繁殖，但这些尚未获得遗传研究。这项研究将部署一个组合 不兼容的映射和种群基因组学以识别特定的不兼容基因以进行进一步研究， 它将提高对生殖隔离最早阶段的遗传结构的理解。 最后，这项研究将阐明基因组多样性和适应潜力的决定因素。这 工作将具有有关中性和适应性遗传相对作用的实验和计算研究 将来适应的多样性，以及量化每个的最相关方法。它还将调查亲戚 不同类型的自然选择在塑造基因组多样性中的重要性，包括探测效用 种群之间的遗传分化以分离阳性和负选择的信号。 总的来说，这项研究对基本进化遗传学是高度的。它也保持强大 医学相关性就局部适应和上学与人类遗传基础的相关性而言 疾病和不育，以及了解昆虫疾病载体的进化动力学。