Department of Biology, American University, Washington, DC 20016, USA.
Genetics. 2010 Feb;184(2):547-55. doi: 10.1534/genetics.109.111294. Epub 2009 Dec 4.
Although most amino acids can be encoded by more than one codon, the synonymous codons are not used with equal frequency. This phenomenon is known as codon bias and appears to be a universal feature of genomes. The translational selection hypothesis posits that the use of optimal codons, which match the most abundant species of isoaccepting tRNAs, results in increased translational efficiency and accuracy. Previous work demonstrated that the experimental reduction of codon bias in the Drosophila alcohol dehydrogenase (Adh) gene led to a significant decrease in ADH protein expression. In this study we performed the converse experiment: we replaced seven suboptimal leucine codons that occur naturally in the Drosophila melanogaster Adh gene with the optimal codon. We then compared the in vivo ADH activities imparted by the wild-type and mutant alleles. The introduction of optimal leucine codons led to an increase in ADH activity in third-instar larvae. In adult flies, however, the introduction of optimal codons led to a decrease in ADH activity. There is no evidence that other selectively constrained features of the Adh gene, or its rate of transcription, were altered by the synonymous replacements. These results are consistent with translational selection for codon bias being stronger in the larval stage and suggest that there may be a selective conflict over optimal codon usage between different developmental stages.
尽管大多数氨基酸可以由多个密码子编码，但同义密码子的使用频率并不相同。这种现象被称为密码子偏好性，似乎是基因组的普遍特征。翻译选择假说认为，使用与最丰富的同功 tRNA 种类匹配的最佳密码子可以提高翻译效率和准确性。先前的工作表明，在果蝇醇脱氢酶（Adh）基因中实验性降低密码子偏好性会导致 ADH 蛋白表达显著减少。在这项研究中，我们进行了相反的实验：我们用最优密码子替换了果蝇 Adh 基因中自然存在的七个次优亮氨酸密码子。然后，我们比较了野生型和突变型等位基因赋予的体内 ADH 活性。引入最优亮氨酸密码子可增加三龄幼虫中的 ADH 活性。然而，在成年果蝇中，引入最优密码子会导致 ADH 活性降低。没有证据表明 Adh 基因的其他受选择限制特征或其转录率因同义替换而改变。这些结果与在幼虫阶段对密码子偏好性的翻译选择更强的观点一致，并表明在不同发育阶段，最优密码子使用可能存在选择冲突。
