Role of mutation rate variation in patterns of molecular evolution in Drosophia

突变率变异在果蝇分子进化模式中的作用

• 批准号: 7463832
• 负责人: Nadia D Singh
• 金额: $ 4.96万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7463832
• 关键词: Address; Class; Code; DNA; DNA Sequence; DNA Transposable Elements; Data; Drosophila genome; Drosophila genus; Drosophila melanogaster; Elements; Environment; Evolution; Gene Conversion; Generations; Genes; Genetic Drift; Genetic Polymorphism; Genetic Recombination; Genetic Variation; Genome; Genomics; Goals; Heterogeneity; Insecta; Introns; Light; Link; Long Terminal Repeats; Mammals; Modeling; Molecular; Molecular Evolution; Mutation; Natural Selections; Nucleotides; Organism; Pattern; Process; Public Health; Rate; Relative (related person); Research; Research Training; Role; Shapes; Site; Surveys; Testing; Variant; comparative; insight; novel; pathogen; sex; theories; tool development

DESCRIPTION (provided by applicant): The long-term goal of the proposed research is to disentangle the contributions of the forces that govern the evolution of the Drosophila genome. In particular, this project focuses on the role of mutation rate variation in patterns of molecular evolution in Drosophila melanogaster. Since mutational generation of novel allelic variants is the first step of the molecular evolutionary process, understanding the effects of heterogeneity in mutation rate on the evolution of coding and noncoding sequences will contribute greatly to the understanding of molecular evolutionary dynamics of the D. melanogaster genome. To address this question, I will first establish an appropriate neutral mutational model for DNA sequence evolution and then use this null model for hypothesis-driven testing to investigate patterns of evolution in functional portions of the genome. Specifically, I propose to characterize the neutral mutational spectrum in the Drosophila melanogaster genome by surveying polymorphism in unconstrained dead-on arrival (DOA) non-long-terminal-repeat (non-LTR) retrotransposable elements. By comparing the polymorphism and divergence spectra of these sequences I can test whether these sequences are evolving in a manner that is consistent with neutrality and potentially validate the approach of using substitutional patterns from unconstrained sequences to infer the underlying mutational process. Beyond characterizing the mutational spectrum and validating the neutrality of DOA sequences, these polymorphism and divergence data can inform our understanding of the role of single-nucleotide mutations in generating observed substitutional patterns at adjacent coding and noncoding regions, and will therefore be applied in two additional contexts. I will first test whether mutation rate variation alone is sufficient to explain the extensively documented heterogeneity in rates and patterns of substitution in this organism by comparing polymorphism and divergence spectra from different parts of the genome previously documented to have significantly different substitutional profiles. Second, I will use these polymorphism and divergence data from the DOA elements to evaluate the contribution of mutation rate variation and selection to rates of evolution in adjacent coding and noncoding sequences in the D. melanogaster genome. This proposed research is relevant to public health in that the findings will deepen our understanding of the forces that shape genome evolution, and will contribute to the development of tools for comparative functional annotation of genomes of organisms as diverse as insects, mammals, and pathogens.

描述（由申请人提供）：拟议的研究的长期目标是解除控制果蝇基因组进化的力的贡献。特别是，该项目的重点是突变率变化在果蝇中分子进化模式中的作用。由于新型等位基因变体的突变产生是分子进化过程的第一步，因此了解异质性在突变速率中的影响对编码和非编码序列的演变的影响将极大地有助于理解D. melanogaster基因组的分子进化动力学。 为了解决这个问题，我将首先建立一个适当的DNA序列演化中性突变模型，然后将此空模型用于假设驱动的测试来研究基因组功能部分的进化模式。具体而言，我建议通过调查无约束的死亡到达（DOA）非长末端重复（非LTR）后逆转录元件中的多态性来表征果蝇中性突变谱。通过比较这些序列的多态性和差异光谱，我可以测试这些序列是否以与中性一致的方式演变，并有可能验证使用不受约束序列的替代模式来推断基本突变过程的方法。 除了表征突变光谱并验证DOA序列的中立性外，这些多态性和差异数据还可以告知我们对单核苷酸突变在相邻编码和非编码区域产生观察到的替代模式中的作用的理解，因此将在另外两个环境中应用。我将首先测试是否仅凭突变率变化足以解释该生物体中替代速率和替代模式的广泛记录的异质性，通过比较以前记录的基因组的多态性和差异光谱，这些基因组的不同部分具有明显不同的取代曲线。其次，我将使用来自DOA元素的这些多态性和差异数据来评估突变速率变化和选择对近相邻的编码和非编码序列进化速率的贡献。 这项拟议的研究与公共卫生有关，因为这些发现将加深我们对塑造基因组进化的力的理解，并将有助于开发工具，用于对像昆虫，哺乳动物和病原体这样多样化的生物体基因组进行比较功能注释。