大肠杆菌中高度丰富的蛋白质基因避免了促进核糖体启动的5'编码子
Loveday E Lewin1, Kate G Daniels1, Laurence D Hurst1
1The Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, United Kingdom.
PLoS computational biology
|October 25, 2023
概括
高度表达的基因在开始时不会使用"最佳"密码子. 相反,在开始附近的编码子使用会影响蛋白质水平,但由于相互冲突的选择压力,本地基因会避免最佳编码子.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 高表达基因 (HEGs) 经常使用同义代码与丰富的tRNA相匹配,称为"翻译最佳"代码.
- 然而,细菌转基因实验表明,这些最佳的编码子对蛋白质水平的影响最小.
- 核糖体启动被认为是限制速率的,这表明上游编码子显著影响蛋白质输出,可能通过RNA稳定性.
研究的目的:
- 为了确定使用HEGs的5'码子丰富的可行性,以定义"启动最佳性" (IO) 评分.
- 通过计算来预测蛋白质水平,并了解细菌转基因设计对同义突变的选择.
- 通过对大肠杆菌进行大规模的转基因实验,客观地定义导致高蛋白质丰度的5'编码子.
主要方法:
- 对本地大肠杆菌基因进行了广泛的蛋白质丰度数据分析.
- 使用一个大规模的细菌转基因密码子随机化实验.
- 将高度表达的本地基因与低表达基因的5'编码子使用情况进行比较.
主要成果:
- 令人惊的是,原生HEGs启动高度丰富的蛋白质避免了它们的5'端的翻译性最佳子.
- 相互矛盾的选择压力,如有利于较低的启动率来提高核糖体效率和降低噪声,可能解释了本地HEG中这种观察.
- 经典的HEG丰富方法未能预测来自5'编码子含量的原生蛋白质丰度.
结论:
- 使用原生HEGs的5'编码丰富的经典方法对于预测蛋白质丰富性是不可行的.
- 从转基因实验中获得的启动最佳性得分可能与体细菌转基因设计相关.
- 了解5'端的编码子使用对于控制蛋白质水平至关重要,但本地基因策略与简单的最佳性原则有所不同.
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