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内，沉默或同义突变（不改变 DNA 编码的氨基酸的突变）被认为对于自然选择是中性的。最近对多种生物体的分析表明，这种假设并不总是正确的。几乎可以肯定的是，由于同义密码子赋予信息翻译效率差异，选择可以检测同义突变。然而，理论和实证研究都表明，选择水平非常弱，可能处于漂移或选择在决定动态过程中占主导地位的边界。因此，大多数对这种稍微有害的突变（分子进化的一个主要特征）的研究仅限于分析统计审查（而不是经验实验操作）。新出现的十二种果蝇完整基因组序列为研究分子进化的这一重要特征提供了迄今为止无法获得的机会。我们在此提案中重点关注决定密码子使用的因素，特别是非随机或有偏见的密码子使用。研究包括，首先，为 12 种果蝇定义最佳密码子，以记录在大约 40-50 年的进化过程中密码子使用发生了多少变化。将探讨密码子使用偏倚水平与基因表达水平和时间（通过发育）的关系，假设表达较高的基因具有较大的密码子使用偏倚，并且这与同接受 tRNA 的水平有关有时在不同的发展阶段会发生变化。这将需要对特定氨基酸进行分析。系统发育的视角将解决诸如选择、突变和漂移在决定密码子使用变化方面的相对作用等问题。密码子使用偏差的一种假设认为，氨基酸的错误掺入是使用最佳密码子的主要驱动因素。这一假设将通过对正在出现的新的完整基因组的分析来检验。最后，我们将研究重组水平对分子变异水平和模式（包括密码子使用）的作用。这是因为在大多数物种中，一条染色体（“点”）上的基因几乎不重组，但在 D. willistoni（正在测序的物种之一）中，它们已被纳入正常重组的染色体中。