Structural variation population size and the evolution of genome complexity

项目摘要 这项建议的主要目标是确定突变如何改变基因组结构(例如， 染色体片段的复制或删除)被获取和保存。要做到这一点， 决定这种突变命运的进化力量将通过对种群进行测序来推断 果蝇的几个种群。结构变异是基因新颖性的重要来源，而且 认为在遗传复杂性的起源中起着重要作用。对结构的总体认识 变异很重要，因为它在癌症的病因学、病原体的出现等方面发挥着重要作用 抗药性，以及动植物病虫害的抗药性起源，以及许多其他主题 与人类健康和福祉相关。 该项目将通过研究亲缘关系密切的果蝇物种对的基因组变异来实施。在……里面 为了理清遗传漂移和自然选择的影响，全基因组测序数据 将收集种群数量差异较大的物种对。这种方法行得通。 因为，随着种群变得越来越小，遗传漂移越来越多地主导着遗传变异。相反， 随着种群的扩大，遗传漂移对遗传变异的影响越来越小。因此， 据预测，当自然选择驱动结构突变的获得和维持时， 与较小的种群相比，较大的种群将获得和保持更多的变异。然而，如果基因漂移是 主要因素，那么较小的种群比较大的种群获得和保持更多的变异。 该项目分为三个主要阶段。第一个是收集和组装参考基因组数据 每个物种，这将使用长分子测序策略来完成。第二个是收集 用于对结构变异进行基因分型的群体测序数据。最后一个阶段是基因组合。 和基因注释，并对它们进行进化分析，以解决上面提出的问题。

Project Summary The primary goal for this proposal is to determine how mutations that change genome structure (e.g. duplications or deletions of sections of chromosomes) are acquired and preserved. To accomplish this, the evolutionary forces that govern the fate of such mutations will be inferred by sequencing populations within several species groups of Drosophila. Structural variation is an important source of genetic novelty and is thought to play an important role in the origin of genetic complexity. A general understanding of structural variation is important because it plays major roles in the etiology of cancer, the emergence of pathogen resistance, and the origin of pesticide resistance for plant and animal crop pests, among many other topics of relevance to human health and well-being. The project will be executed by studying genomic variation in pairs of closely related Drosophila species. In order to disentangle the influence of genetic drift and natural selection, genome-wide sequencing data for species pairs that exhibit large differences in their population sizes will be collected. This approach works because, as populations become smaller, genetic drift dominates genetic variation more and more. Conversely, as populations become larger, genetic drift's influence on genetic variation becomes weaker and weaker. Thus, it is predicted that, when natural selection drives the acquisition and maintenance of structural mutations, larger populations will acquire and maintain more variants than smaller ones. However, if genetic drift is the major factor, then smaller populations acquire and maintain more variants than larger ones. The project is split into three major phases. The first is collection of and assembly of reference genome data for each species, which will be done using long molecule sequencing strategies. The second is collection of population sequencing data for use in genotyping structural variants. The final phase is to combine genotype and gene annotations and subject them to evolutionary analysis to address the questions proposed above.