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

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）：在相当长的一段时间里，沉默突变或同义突变（不改变DNA编码的氨基酸的突变）被认为是自然选择的中性突变。最近对各种生物体的分析表明，这种假设并不总是正确的。几乎可以肯定，由于同义密码子在信息翻译效率上的差异，选择可以检测到同义突变。然而，理论和实证研究都表明，选择的水平非常弱，可能处于漂移或选择在决定动力学方面占主导地位的边缘。因此，对这种轻微有害突变（分子进化的一个主要特征）的大多数研究都局限于分析性统计审查（与经验实验操作相反）。12种果蝇的完整基因组序列的出现为研究分子进化的这一重要特征提供了一个迄今为止无法获得的机会。我们在这个建议集中在决定密码子使用的因素，特别是非随机或有偏差的密码子使用。研究包括，首先，确定12种果蝇的最佳密码子，以记录密码子的使用在大约40-50万年的进化过程中发生了多少变化。我们将探索密码子使用偏差水平与基因表达水平和时间（通过发育）的关系，假设高表达的基因具有更大的密码子使用偏差，以及这与在发育阶段有时发生变化的等容tRNA池的水平有关。这需要分析特定的氨基酸。系统发育的观点将解决诸如选择，突变和漂移在决定密码子使用变化中的相对作用等问题。一种关于密码子使用偏差的假设认为，氨基酸的错误结合是使用最佳密码子的主要驱动因素；这一假设将通过对新出现的完整基因组的分析得到验证。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上的作用。这是可能的，因为在大多数物种中，一条染色体（“点”）上的基因几乎是不重组的，但在d.w illistoni中，一条正常重组的染色体被合并了，这是正在测序的物种之一。