Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
PLoS One. 2010 Aug 17;5(8):e11935. doi: 10.1371/journal.pone.0011935.
Every protein has a biosynthetic cost to the cell based on the synthesis of its constituent amino acids. In order to optimise growth and reproduction, natural selection is expected, where possible, to favour the use of proteins whose constituents are cheaper to produce, as reduced biosynthetic cost may confer a fitness advantage to the organism. Quantifying the cost of amino acid biosynthesis presents challenges, since energetic requirements may change across different cellular and environmental conditions. We developed a systems biology approach to estimate the cost of amino acid synthesis based on genome-scale metabolic models and investigated the effects of the cost of amino acid synthesis on Saccharomyces cerevisiae gene expression and protein evolution. First, we used our two new and six previously reported measures of amino acid cost in conjunction with codon usage bias, tRNA gene number and atomic composition to identify which of these factors best predict transcript and protein levels. Second, we compared amino acid cost with rates of amino acid substitution across four species in the genus Saccharomyces. Regardless of which cost measure is used, amino acid biosynthetic cost is weakly associated with transcript and protein levels. In contrast, we find that biosynthetic cost and amino acid substitution rates show a negative correlation, but for only a subset of cost measures. In the economy of the yeast cell, we find that the cost of amino acid synthesis plays a limited role in shaping transcript and protein expression levels compared to that of translational optimisation. Biosynthetic cost does, however, appear to affect rates of amino acid evolution in Saccharomyces, suggesting that expensive amino acids may only be used when they have specific structural or functional roles in protein sequences. However, as there appears to be no single currency to compute the cost of amino acid synthesis across all cellular and environmental conditions, we conclude that a systems approach is necessary to unravel the full effects of amino acid biosynthetic cost in complex biological systems.
每种蛋白质的生物合成成本都取决于其组成氨基酸的合成，基于这一点，细胞会进行优化选择，尽可能选择使用组成氨基酸成本更低的蛋白质，因为降低生物合成成本可能会给生物体带来适应性优势。由于能量需求可能会因不同的细胞和环境条件而发生变化，因此量化氨基酸生物合成的成本具有一定的挑战性。我们开发了一种系统生物学方法，根据基因组规模的代谢模型来估计氨基酸合成的成本，并研究了氨基酸合成成本对酿酒酵母基因表达和蛋白质进化的影响。首先，我们使用了两种新的和之前报告的六种氨基酸成本度量方法，结合密码子使用偏好、tRNA 基因数量和原子组成，来确定这些因素中哪些因素能最好地预测转录本和蛋白质水平。其次，我们比较了氨基酸成本与四个酿酒酵母属物种中的氨基酸替换率。无论使用哪种成本度量方法，氨基酸生物合成成本与转录本和蛋白质水平都呈弱相关。相比之下，我们发现生物合成成本与氨基酸替换率呈负相关，但仅对于部分成本度量方法而言。在酵母细胞的经济体系中，与翻译优化相比，我们发现氨基酸合成的成本在塑造转录本和蛋白质表达水平方面所起的作用有限。然而，生物合成成本似乎确实会影响酿酒酵母中氨基酸的进化速率，这表明在蛋白质序列中，只有当昂贵的氨基酸具有特定的结构或功能作用时，才会使用它们。然而，由于在所有细胞和环境条件下计算氨基酸生物合成成本似乎没有单一的货币，因此我们得出结论，需要采用系统方法才能揭示氨基酸生物合成成本在复杂生物系统中的全部影响。
