Evolutionary systems biology of amino acid biosynthetic cost in yeast.
Evolutionary systems biology of amino acid biosynthetic cost in yeast.
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DOI：
10.1371/journal.pone.0011935
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发表时间：
2010-08-17
期刊：
影响因子：
3.7
通讯作者：
Bergman CM
中科院分区：
文献类型：
--
作者：
Barton MD;Delneri D;Oliver SG;Rattray M;Bergman CM
每一种蛋白质对细胞都有生物合成成本，这是基于其组成氨基酸的合成。为了优化生长和繁殖，在可能的情况下，自然选择倾向于使用生产成本较低的蛋白质，因为降低的生物合成成本可能赋予生物体适应性优势。量化氨基酸生物合成的成本提出了挑战，因为能量需求可能在不同的细胞和环境条件下发生变化。我们开发了一种基于基因组尺度代谢模型的系统生物学方法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，我们使用了两个新的和六个先前报道的氨基酸成本测量方法，结合密码子使用偏差，tRNA基因数量和原子组成来确定哪些因素最能预测转录物和蛋白质水平。其次，我们比较了糖酵母菌属中四个物种的氨基酸成本和氨基酸取代率。无论使用哪种成本测量方法，氨基酸生物合成成本与转录物和蛋白质水平的相关性都很弱。相比之下，我们发现生物合成成本和氨基酸取代率呈负相关，但只是成本措施的一个子集。在酵母细胞的经济中，我们发现与翻译优化相比，氨基酸合成的成本在塑造转录本和蛋白质表达水平方面起着有限的作用。然而，生物合成成本似乎确实影响了酵母菌中氨基酸的进化速度，这表明昂贵的氨基酸可能只在它们在蛋白质序列中具有特定的结构或功能作用时才被使用。然而，由于似乎没有单一货币来计算所有细胞和环境条件下氨基酸合成的成本，我们得出结论，有必要采用系统方法来揭示复杂生物系统中氨基酸生物合成成本的全部影响。
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.
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