Analysis of Eukaryotic Compositional and Codon Biases

真核生物组成和密码子偏差分析

• 批准号: 6315784
• 负责人: RICHARD M KLIMAN
• 金额: $ 3.25万
• 依托单位: KEAN UNIVERSITY
• 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 2002-07-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6315784
• 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）：该项目旨在表征 对重要真核基因组组成的各种影响 模型生物（酵母菌，秀丽隐杆线虫和果蝇Melanogaster）。一个 基因组可以看作是核苷酸的顺序排列，每个核苷酸 可以在整个过程中用任何其他核苷酸替换（突变） 进化。根据环境和遗传环境，突变将是 有害，有益或中立。那些确实会影响健康的突变（ 个人有能力为子孙后代做出贡献） 选择，而所有突变都存在突变偏见。事先的 分析，特别是在水果蝇和温血脊椎动物上的分析 该碱基组成（四个核苷酸的相对使用）各种 跨基因组。在水果苍蝇中，有几个嵌套的水平 组成变化。一些组成变化与 同义密码子的使用，该密码子在许多生物中都可以选择 其对蛋白质合成的影响的基础。过去的主要限制 关于密码子使用和基础组成的研究一直是自信的数量 测序基因。但是，由于模型生物的基因组序列是 在很大程度上完成，我们可以构建数千个基因的数据集 更好地解析碱成分变化的模式。我们也可以更好 描述密码子的使用偏见，并估计自然的相对影响 组成偏差的选择和区域变化。考虑到这一点 我们建议分析选定的组成和密码子偏见 真核生物使用相关统计方法已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。对模型中DNA序列演变的更深入了解 有机体将为未来的分析提供有用的对比度 人类基因组序列。此外，该项目将提供一组 统计工具以及计算机程序，用于组成分析 非常大的DNA序列数据集。