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

描述(申请人提供)：基因复制是真核生物基因组中普遍存在的特征。然而，我们对导致它们保存在基因组中或从基因组中丢失的进化力量知之甚少。这项拟议的研究涉及对三个果蝇物种--黑腹果蝇、拟果蝇和雅库巴果蝇的重复基因座进行重新测序。我们还将使用Illumina Genome Analyzer平台获得配对测序数据，以调查D.Simans和D.Yakuba物种的分离复制。重测序数据集将用于量化重复基因座内选择性约束的程度和重复基因座之间的适应性差异。此外，这些数据将为该属异位基因转化的程度提供有价值的见解。配对数据将被用来推断所有三个物种的编码和非编码重复的频谱，并量化这种分离变异可能有害或适应的程度。我们还将使用这些数据来寻找基因组中多态和复制分歧可能分离的区域，表明自然选择在基因家族进化中的作用。 公共卫生相关性：随着时间的推移，基因的得失是基因组结构进化的主要因素，而基因数量的变化是人类群体中表型变异和疾病的一个因素。这项研究将以果蝇黑腹果蝇为模型系统，阐明作用于最近复制的基因的各种进化力量，包括那些固定在物种内的基因以及那些分离的多态基因。拟议研究的设计是为了补充果蝇种群基因组计划(DPGP，http://www.dpgp.org)，)，该计划近期的重点是研究黑腹果蝇，提供该属另外两个物种--拟果蝇和雅库巴果蝇的重复基因座和结构多态的比较数据。1

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