Population genetics of gene duplications and copy-number variants in the Drosophi

果蝇基因重复和拷贝数变异的群体遗传学

• 批准号: 8111703
• 负责人: Kevin R. Thornton
• 金额: $ 23.63万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111703
• 关键词: African; Automobile Driving; Biological Models; Biological Preservation; Cations; Cells; Chromosome Arm; Code; Communities; Complement; DNA Resequencing; Data; Data Set; Detection; Disease; Drosophila genus; Drosophila melanogaster; Evolution; Family member; Frequencies; Functional RNA; Gene Conversion; Gene Duplication; Gene Family; Genes; Genetic Polymorphism; Genome; Genomics; Goals; Hot Spot; Human; Methods; Natural Selections; Nucleotides; Partner in relationship; Pattern; Population; Population Genetics; Process; Publishing; Recording of previous events; Research; Research Design; Role; Sampling; Site; Statistical Methods; Structure; Subgroup; Surveys; Technology; Time; Variant; comparative; design; duplicate genes; genome sequencing; insight; paralogous gene; public health relevance

DESCRIPTION (provided by applicant): Gene duplications are a ubiquitous feature of eukaryotic genomes. However, we know relatively little about the evolutionary forces responsible for their preservation in, or loss from, the genome. The proposed research involves a resequencing survey of duplicated loci in three Drosophila species, D. melanogaster, D. simulans, and D. yakuba. We will also obtain mate pair sequencing data using the Illumina Genome Analyzer platform to survey D. simulans and D. yakuba species for segregating duplications. The resequencing data set will be used to quantify the extent of selective constraint within, and adaptive divergence between duplicated loci. Additionally, these data will provide valuable insight on the extent of ectopic gene conversion in the genus. The mate pair data will be used to infer the frequency spectrum of coding and non-coding duplications in all three species, and to quantify the extent to which such segregating variation may be deleterious or adaptive. We will also use these data to look for regions of the genome where polymorphism and divergence for duplication may be uncoupled, indicating a role for natural selection on the evolution of gene families. PUBLIC HEALTH RELEVANCE: The gain and loss of genes over time is a major contributor to the evolution of genome structure, and variation in the number of genes is a contributor to phenotypic variation and disease within human populations. This study will use the fruit fly Drosophila melanogaster as a model system to elucidate the various evolutionary forces acting on recently duplicated genes, including those that are fixed within species as well as those segregating as polymorphisms. The design of the proposed research is intended to complement the Drosophila Population Genomics Project (DPGP, http://www.dpgp.org), which is focusing its near-term effort on D. melanogaster, by providing comparative data on duplicate loci and structural polymorphism in two other species from the genus, D. simulans and D. yakuba. 1

描述（由申请人提供）：基因复制是真核生物基因组的普遍特征。然而，我们对它们在基因组中保存或丢失的进化力量知之甚少。这项研究涉及对三种果蝇的重复基因座进行重测序。melanogaster、黑腹杜父鱼D. simulans和D.日本料理。我们还将使用Illumina基因组分析仪平台获得配偶对测序数据，以调查D。simulans和D. yakuba种分离重复。重测序数据集将用于量化重复基因座内的选择性约束程度和重复基因座之间的适应性分歧。此外，这些数据将提供有价值的见解的程度异位基因转换的属。配偶对数据将被用来推断在所有三个物种的编码和非编码重复的频谱，并量化这种分离的变化可能是有害的或适应的程度。我们还将使用这些数据来寻找基因组的多态性和重复的分歧可能是解耦的区域，表明自然选择对基因家族进化的作用。 公共卫生相关性：随着时间的推移，基因的获得和丢失是基因组结构进化的主要贡献者，基因数量的变化是人类群体中表型变异和疾病的贡献者。本研究将使用果蝇作为一个模型系统来阐明各种进化力量作用于最近复制的基因，包括那些固定在物种内，以及那些分离的多态性。这项研究的设计是为了补充果蝇种群基因组学项目（DPGP，http://www.dpgp.org），该项目的近期工作重点是D。melanogaster的重复基因座和结构多态性的比较数据。simulans和D.日本料理。1