Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.
PLoS One. 2012;7(11):e48542. doi: 10.1371/journal.pone.0048542. Epub 2012 Nov 7.
Different codons encoding the same amino acid are not used equally in protein-coding sequences. In bacteria, there is a bias towards codons with high translation rates. This bias is most pronounced in highly expressed proteins, but a recent study of synthetic GFP-coding sequences did not find a correlation between codon usage and GFP expression, suggesting that such correlation in natural sequences is not a simple property of translational mechanisms. Here, we investigate the effect of evolutionary forces on codon usage. The relation between codon bias and protein abundance is quantitatively analyzed based on the hypothesis that codon bias evolved to ensure the efficient usage of ribosomes, a precious commodity for fast growing cells. An explicit fitness landscape is formulated based on bacterial growth laws to relate protein abundance and ribosomal load. The model leads to a quantitative relation between codon bias and protein abundance, which accounts for a substantial part of the observed bias for E. coli. Moreover, by providing an evolutionary link, the ribosome load model resolves the apparent conflict between the observed relation of protein abundance and codon bias in natural sequences and the lack of such dependence in a synthetic gfp library. Finally, we show that the relation between codon usage and protein abundance can be used to predict protein abundance from genomic sequence data alone without adjustable parameters.
不同的密码子编码相同的氨基酸在蛋白质编码序列中使用并不平等。在细菌中,存在着对高翻译速率密码子的偏好。这种偏好在高表达蛋白中最为明显,但最近对合成 GFP 编码序列的研究并没有发现密码子使用与 GFP 表达之间的相关性,这表明在自然序列中这种相关性不是翻译机制的简单特性。在这里,我们研究进化力量对密码子使用的影响。基于密码子偏好是为了确保核糖体有效利用这一假设,对密码子偏好与蛋白质丰度的关系进行了定量分析,核糖体是快速生长细胞的宝贵资源。根据细菌生长规律,建立了一个明确的适应度景观,将蛋白质丰度和核糖体负荷联系起来。该模型得出了密码子偏好与蛋白质丰度之间的定量关系,该关系解释了大肠杆菌中观察到的偏好的很大一部分。此外,通过提供一种进化联系,核糖体负荷模型解决了在自然序列中观察到的蛋白质丰度和密码子偏好之间的明显冲突,以及在合成 gfp 文库中缺乏这种依赖性的问题。最后,我们表明,密码子使用与蛋白质丰度之间的关系可以用来仅从基因组序列数据预测蛋白质丰度,而无需可调参数。