Evolution of codon usage bias in the genus Drosophila

果蝇属密码子使用偏差的进化

• 批准号: 7080559
• 负责人: Jeffrey R POWELL
• 金额: $ 15.79万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7080559
• 关键词: Drosophilidae; arthropod genetics; developmental genetics; gene mutation; natural selections; protein sequence; species difference; transfer RNA; Drosophilidae; arthropod genetics; developmental genetics; gene mutation; natural selections; protein sequence; species difference; transfer RNA

DESCRIPTION (provided by applicant): For a considerable time, silent or synonymous mutations (mutations that do not change the amino acid being coded by DNA) were assumed to be neutral with respect to natural selection. Recent analyses of a variety of organisms indicate that this assumption is not always correct. Almost certainly due to the fact that synonymous codons confer differences in efficiency of translation of messages, selection can detect synonymous mutations. However, both theoretical and empirical studies indicate that the level of selection is very weak, probably on the border of when drift or selection predominates in determining the dynamics. Thus, most studies of such slightly deleterious mutations, a major feature of molecular evolution, are confined to analytical statistical scrutiny (as opposed to empirical experimental manipulations). The emerging set of complete genome sequences for twelve species of well understood Drosophila provides a heretofore unavailable opportunity to study this important feature of molecular evolution. We focus in this proposal on the factors that determine codon usage, especially non-random or biased codon usage. Studies include, first, defining optimal codons for the twelve species of Drosophila to document how much codon usage has changed during the approximately 40-50 MY of evolution. The relationship of level of codon usage bias to both the level and timing (through development) of expression of genes will be explored, with the hypothesis that genes with higher expression have greater codon usage bias as well as this being related to levels of isoaccepting tRNA pools that sometimes change across developmental stages. This will require analysis of specific amino acids. A phylogenetic perspective will address issues such as the relative role of selection, mutation, and drift in determining changes in codon usage. One hypothesis for codon usage bias asserts that misincorporation of amino acids is a major driving factor for usage of optimal codons; this hypothesis will be tested by analysis of the emerging new complete genomes. Finally, we will examine the role of levels of recombination on level and patterns of molecular variation including codon usage. This is made possible by the fact that genes on one chromosome (the "dot") are nearly non- recombining in most species, but have been incorporated into a normally recombining chromsome in D. willistoni, one of the species being sequenced.

描述（由申请人提供）：在相当长的时间内，假定相对于自然选择，假定静音或同义突变（不改变由DNA编码的氨基酸）是中性的。对各种生物的最新分析表明，这种假设并不总是正确的。几乎可以肯定，由于同义密码子赋予了消息翻译效率差异，因此选择可以检测同义突变。但是，理论和经验研究都表明，选择水平非常弱，可能在确定动力学时占主导地位的边界。因此，大多数对这种有害突变的研究（分子进化的主要特征）仅限于分析统计检查（与经验实验操作相对）。十二种知识良好的果蝇的新兴基因组序列集提供了一个迄今无法可用的机会，可以研究分子进化的这一重要特征。我们将重点放在确定密码子使用情况的因素上，尤其是非随机或偏见的密码子使用情况。研究首先定义了十二种果蝇的最佳密码子，以记录在大约40-50我的进化过程中使用多少密码子的使用情况。将探索密码子使用偏见与定时和定时（通过发展）基因表达的水平的关系，假设具有较高表达的基因具有较大的密码子使用偏置，以及与有时在整个发育阶段变化的ISOACOCECECT的tRNA库水平有关的基因。这将需要分析特定的氨基酸。系统发育的观点将解决诸如选择，突变和漂移在确定密码子使用变化中的相对作用之类的问题。密码子使用偏见的一种假设断言，氨基酸的掺杂是使用最佳密码子的主要驱动因素。该假设将通过分析新出现的完整基因组来检验。最后，我们将研究重组水平在包括密码子使用在内的分子变异水平和模式中的作用。一个事实是，一个染色体上的基因（“点”）在大多数物种中几乎不重组，但已被掺入正常重新组合的D. Willistoni中，这是一个被测序的物种之一。