Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast
Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast
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DOI：
10.1038/nature02636
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发表时间：
2004-06-10
期刊：
影响因子：
64.8
通讯作者：
Hurst, LD
中科院分区：
文献类型：
--
作者：
Papp, B;Pál, C;Hurst, LD
在实验室条件下，80% 的酵母基因似乎对于生存能力不是必需的(1)。这就提出了一个问题：可分配性的机械基础是什么，以及它是缓冲选择的结果还是偶然的副产品。在这里，我们使用酵母代谢网络的计算机通量模型 (2-5) 来分析这些问题。该模型正确预测了 88% 的研究基因 (4) 的敲除适应性效应和体内通量。可有可无的基因可能很重要，但在实验室尚未检查的条件下。我们的模型表明，这是对表观可有可无性的主要解释，占可有可无基因的 37 - 68%，而其中 15 - 28% 由重复基因补偿，只有 4 - 17% 通过代谢网络通量重组进行缓冲。对于一半以上在营养丰富的条件下不重要的情况，我们可以预测它们何时会变得重要。正如预期的那样，此类条件特异性基因具有更受限制的系统发育分布。对于必不可少的反应来说，催化相同反应的基因重复并不常见，这表明保留它们的原因不是为了提供补偿。相反，它们的存在可以通过选择高酶通量来更好地解释。
Under laboratory conditions 80% of yeast genes seem not to be essential for viability(1). This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model(2-5) of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied(4) and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37 - 68% of dispensable genes, whereas 15 - 28% of them are compensated by a duplicate, and only 4 - 17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.