Genetic variation, admixture and genome structure evolution through the lense of Drosophila genomics

对遗传模式生物的研究是表征突变和 产生遗传和表型多样性的选择性过程。特别是，果蝇结合了 有效的人口抽样优势，成熟的实验技术，强大的基因组 工程学的方法，因此是唯一有价值的系统来表征的贡献 自然群体遗传变异对表型变异和适合度变异的影响。为了这个宏大的目标，这个 研究计划将利用D.Blackogaster系统来： (1)增强果蝇基因组连接(DGN)，这是一个广泛使用的数据库，均匀分布 精选和高质量的果蝇种群基因组变异数据集。具体来说，通过开发 包括已知遗传变异的方法，而不是映射到单个单倍体参考基因组，这 研究计划将增强单核苷酸多态的变异调用以及扩大我们的 能够发现和准确描述结构变化。同样，研究将开发和应用 准确描绘近交系基因组杂合区的方法。以极大的 通过对数据库的完善，这一研究将对广泛使用的DGN进行新一轮的深入分析。 (2)揭示结构和连锁等位基因变异的适合度和基因表达结果 与自然的染色体倒置有关。基因组工程技术使构建 在基因同源背景上具有受控断点的倒置。与…形成鲜明对比 自然发生的染色体倒置，研究将区分结构等位基因和连锁等位基因的影响 基因表达模式的变异。此外，研究将调查罚款对健康的影响- 断点位置的刻度变化。染色质构象捕获测序，Hi-C，将使 生产测序文库，其大的插入大小能够进行反转断点作图。研究将会 将此方法应用于映射罕见反转的断点。通过将断点结构与 常见的反转，这些数据将使人们能够直接洞察产生反转的突变力量 以及这些因素如何影响对新的染色体安排的自然选择。 (3)研究不同基因间混合对基因组和表型的影响 亚群。通过对几个混合的黑腹果蝇种群进行测序，研究将确定 基因-基因相互作用在推动不同混合种群的自然选择中的相对重要性。 此外，通过利用来自一个混合种群的表型数据，该混合种群已经使用了许多 协会研究，研究将评估混合物在形成复杂表型方面的重要性 在最初的基因流动事件之后，开发当地祖先意识的方法来定位复杂的性状 联想。

Studies in genetic model organisms are an indispensible mechanism for characterizing the mutational and selective processes that generate genetic and phenotypic diversity. In particular, Drosophila combines the advantages of efficient population sampling, well developed experimental techniques, with powerful genome engineering approaches and is therefore a uniquely valuable system for characterizing the contributions of genetic variation to phenotypic and fitness variation in natural populations. Towards this broad goal, this research program will leverage the D. melanogaster system to: (1) Enhance the Drosophila Genome Nexus (DGN), a widely used database that distributes a uniformly curated and high quality Drosophila population genomic variation dataset. Specifically, by developing methods that include known genetic variation rather than mapping to a single haploid reference genome, this research program will enhance both variation calls at single nucleotide polymorphisms as well as expand our ability to detect and accurately characterize structural variation. Similarly, research will develop and apply approaches for accurately delineating heterozygous regions in the genomes of inbred lines. By vastly improving the database, this reseach will enable a new wave of in-depth analyses of the widely-used DGN. (2) Reveal the fitness and gene expression consequences of the structural and linked allelic variation associated with natural chromosomal inversions. Genome engineering techniques enable the construction of inversions with controlled breakpoints on a genetically homogenous background. Through contrasts with naturally occurring chromosomal inversions, research will distinguish the impacts of structural and linked allelic variation on gene expression patterns. In addition, research will investigate the fitness consequences of fine- scale variation in breakpoint location. Chromatin conformation capture sequencing, Hi-C, will enable the production of sequencing libraries whose large insert sizes enable inversion breakpoint mapping. Research will apply this approach to map breakpoints of rare inversions. By comparing breakpoint structures with those of common inversions, these data will enable direct insights into the mutational forces that generate inversions as well as how these factors influence natural selection on new chromosomal arrangements. (3) Investigate the genomic and phenotypic consequences of admixture between genetically divergent subpopulations. By sequencing several admixed populations of D. melanogaster, research will determine the relative importance of gene-gene interactions in driving natural selection across diverse admixed populations. Furthermore, by leverage phenotypic data from one admixed population that has been used for a number of association studies, research will evaluate the importance of admixture in shaping complex phenotypes long after the initial gene flow event and develop local ancestry aware approaches for mapping complex trait associations.