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

描述（由申请人提供）：基因复制是真核生物基因组普遍存在的特征。然而，我们对它们在基因组中保存或丢失的进化力量所知相对较少。这项拟议的研究包括对三种果蝇（D. melanogaster， D. simulans和D. yakuba）的重复位点进行重测序调查。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物种进行重复分离。重测序数据集将用于量化重复位点内的选择约束程度和自适应差异。此外，这些数据将为该属异位基因转换的程度提供有价值的见解。配偶对数据将用于推断所有三个物种的编码和非编码复制的频谱，并量化这种分离变异可能是有害的还是自适应的程度。我们还将使用这些数据来寻找基因组中多态性和复制分化可能不耦合的区域，这表明自然选择在基因家族进化中的作用。

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