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: 10368935
• 负责人: JOHN E POOL
• 金额: $ 22.88万
• 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/10368935
• 关键词: Address; African; Architecture; Consequentialism; Disease; Drosophila genus; European; Evolution; Future; Generations; Genes; Genetic; Genetic Drift; Genetic Epistasis; Genetic Variation; Genetic study; Genome; Genomics; Heart Diseases; Immune; Individual; Infertility; Medical; Natural Selections; Penetrance; Performance; Population; Portraits; Process; Reproduction; Research; Role; Shapes; Signal Transduction; Spontaneous abortion; System; Time; Transgenic Organisms; Variant; Work; computer studies; cost effective; diabetes risk; disorder risk; experimental study; genetic architecture; genetic resource; genetic variant; 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和不相容的架构 该研究计划解决了遗传与遗传之间相互作用的基本但尚未解决的问题。 变异和进化过程。它特别关注三个相互关联的研究主题：(1) 适应性性状进化的遗传复杂性，（2）早期生殖的遗传基础 隔离，以及（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 使用分析大型基因组数据集的新方法进行具有成本效益的果蝇实验。 黑腹果蝇为这项工作提供了关键的优势。该物种的全球扩张使得 研究不同群体之间的适应性特征差异和部分生殖隔离 过去约一万年。由于最近的时间尺度，可以从遗传变异中检测到适应性差异。 果蝇的实验效率允许对多代的大型实验室群体进行研究。 其紧凑的基因组可以实现经济的测序。一旦找到相关基因，进行功能确认 和研究得到了注释良好的基因组和丰富的遗传资源和转基因工具的帮助。 这项研究将加深对适应性特质进化的遗传复杂性的理解。最初的 研究结果表明，适应的描绘通常始于长期的遗传变异，包括 具有更大效应量的变体，并且具有个体之间可变的遗传结构。拟议的工作 将在多个方面巩固和扩展这些推论，包括启动扩大测绘研究 以获得更广泛的适应性特征，并追寻先前涉及适应性变体的上位性暗示。 拟议的工作还将开辟一个有前途的新系统来研究早期的遗传基础 生殖隔离。非洲和欧洲黑腹果蝇显示出不相容性影响的证据 生存能力和繁殖能力，但这些都没有接受过遗传学研究。本研究将采用组合 不相容性作图和群体基因组学，以确定特定的不相容基因以供进一步研究， 它将促进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 工作将以对中性遗传和适应性遗传的相对作用进行实验和计算研究为特色 未来适应的多样性，以及量化每种多样性的最相关方法。还将对相关人员进行调查 不同类型的自然选择在塑造基因组多样性方面的重要性，包括探索 种群之间的遗传分化，以区分正选择和负选择的信号。 总的来说，这项研究对于基础进化遗传学具有非常重要的意义。也能保持坚挺 就局部适应和上位性与人类遗传基础的相关性而言，医学相关性 疾病和不孕症，以及了解昆虫疾病媒介的进化动态。