Analysis of Eukaryotic Compositional and Codon Biases

真核生物组成和密码子偏差分析

• 批准号: 6609838
• 负责人: RICHARD M KLIMAN
• 金额: $ 7.67万
• 依托单位: CEDAR CREST COLLEGE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2004-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6609838
• 关键词: Caenorhabditis elegans; DNA; Drosophilidae; Saccharomyces cerevisiae; biochemical evolution; computer program /software; eukaryote; gene expression; gene mutation; genome; nucleic acid sequence; population genetics; statistics /biometry

DESCRIPTION (Applicant's Abstract): This project is aimed at characterizing the various influences on the composition of the genomes of important eukaryotic model organisms (yeast, Caenorhabditis elegans and Drosophila melanogaster). A genome can be viewed as a sequential arrangement of nucleotides, each of which can be replaced (by mutation) with any of the other nucleotides over the course of evolution. Depending on environmental and genetic context, mutations will be harmful, beneficial or neutral. Those mutations that do affect fitness (the capacity of the individual to contribute to future generations) are subject to selection, while all mutations are subject to mutational biases. Prior analyses, particularly on fruit flies and warm-blooded vertebrates have shown that base composition (the relative usage of the four nucleotides) varies across the genome. In fruit flies, there are several nested levels of compositional variation. Some compositional variation correlates with synonymous codon usage, which is subject to selection in many organisms on the basis of its influence on protein synthesis. A major limitation in the past for studies on codon usage and base composition has been the number of confidently sequenced genes. However, as the genome sequences of model organisms are largely complete, we can construct data sets of several thousand genes to better resolve the patterns of base composition variation. We can also better describe codon usage bias, and estimate the relative influences of natural selection and regional variation in compositional bias. It is in view of this that we propose to analyze compositional and codon biases in selected eukaryotes using relevant statistical methods that have been developed by the principal investigator, as well as new methods that will be developed as part of the project. A fuller understanding of DNA sequence evolution in model organisms will provide a useful contrast for future analyses on the completed human genome sequence. Furthermore, this project will provide a set of statistical tools, as well as computer programs, for compositional analysis of very large DNA sequence data sets.

描述（申请人的摘要）：该项目旨在描述 对重要真核生物基因组组成的各种影响 模式生物（酵母、秀丽隐杆线虫和果蝇）。一个 基因组可以被视为核苷酸的顺序排列，其中每个核苷酸 可以在整个过程中被任何其他核苷酸替换（通过突变） 进化论。根据环境和遗传背景，突变将 有害、有益或中性。那些确实影响健康的突变（ 个人为子孙后代做出贡献的能力）取决于 选择，而所有突变都受到突变偏差的影响。事先的 分析，特别是对果蝇和温血脊椎动物的分析表明 碱基组成（四种核苷酸的相对使用）不同 跨越基因组。在果蝇中，有几个嵌套的层次 成分变化。一些成分变化与 同义密码子的使用，在许多生物体中受到选择 其对蛋白质合成的影响。过去的一个主要限制 关于密码子使用和碱基组成的研究已经有很多 已测序的基因。然而，由于模式生物的基因组序列 基本完成了，我们可以构建数千个基因的数据集 更好地解决碱基组成变异的模式。我们还可以更好 描述密码子使用偏差，并估计自然密码子的相对影响 选择和成分偏差的区域差异。正是鉴于此 我们建议分析选定的成分和密码子偏差 真核生物使用由该组织开发的相关统计方法 首席研究员，以及将作为一部分开发的新方法 项目的。更全面地了解模型中的 DNA 序列进化 有机体将为未来对已完成的分析提供有用的对比 人类基因组序列。此外，该项目还将提供一套 用于成分分析的统计工具以及计算机程序 非常大的 DNA 序列数据集。