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: 7901679
• 负责人: Kevin R. Thornton
• 金额: $ 23.91万
• 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/7901679
• 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）：基因重复是真核基因组的普遍特征。但是，我们对负责其在基因组中保存或损失的进化力量相对较少。拟议的研究涉及对三种果蝇种类的重复基因座进行重新陈述的调查。我们还将使用Illumina Genome Analyzer平台获得序列对测序数据，以调查D. simulans和D. Yakuba物种，以分离重复。重新定制数据集将用于量化内部选择性约束的程度以及重复的基因座之间的自适应差异。此外，这些数据将提供有关该属异位基因转换程度的宝贵见解。配对对数据将用于推断所有三个物种中编码和非编码重复的频率频谱，并量化这种分离变异可能是有害或适应性的程度。我们还将使用这些数据来寻找基因组的区域，在这些区域中，可以取消多态性和复制的差异，这表明自然选择在基因家族的演变中起作用。 公共卫生相关性：随着时间的推移，基因的增益和丧失是基因组结构演变的主要贡献者，基因数量的变化是人群中表型变异和疾病的贡献者。这项研究将使用果蝇果蝇Melanogaster作为模型系统，以阐明作用于最近重复的基因的各种进化力，包括固定在物种中的基因以及将多态性隔离为多态性的基因。拟议的研究的设计旨在补充果蝇种群基因组学项目（DPGP，http://www.dpgp.org），该项目将其近期的努力集中在D. Melanogaster上，通过在其他两个物种中的重复位点和结构性聚合中的比较数据中提供了比较数据，该物种来自基因和D. simp. d. simp. d. simp. d. simp. d. yakuba and d. y。 1