Department of Biochemistry, University of Zürich, Zürich, Switzerland.
PLoS Comput Biol. 2009 Dec;5(12):e1000613. doi: 10.1371/journal.pcbi.1000613. Epub 2009 Dec 18.
Genome-scale metabolic networks are highly robust to the elimination of enzyme-coding genes. Their structure can evolve rapidly through mutations that eliminate such genes and through horizontal gene transfer that adds new enzyme-coding genes. Using flux balance analysis we study a vast space of metabolic network genotypes and their relationship to metabolic phenotypes, the ability to sustain life in an environment defined by an available spectrum of carbon sources. Two such networks typically differ in most of their reactions and have few essential reactions in common. Our observations suggest that the robustness of the Escherichia coli metabolic network to mutations is typical of networks with the same phenotype. We also demonstrate that networks with the same phenotype form large sets that can be traversed through single mutations, and that single mutations of different genotypes with the same phenotype can yield very different novel phenotypes. This means that the evolutionary plasticity and robustness of metabolic networks facilitates the evolution of new metabolic abilities. Our approach has broad implications for the evolution of metabolic networks, for our understanding of mutational robustness, for the design of antimetabolic drugs, and for metabolic engineering.
基因组规模的代谢网络对于酶编码基因的消除具有高度的鲁棒性。它们的结构可以通过消除这些基因的突变和通过添加新的酶编码基因的水平基因转移而迅速进化。使用通量平衡分析，我们研究了代谢网络基因型的广阔空间及其与代谢表型的关系，即能够在可用碳源谱定义的环境中维持生命的能力。两种这样的网络通常在其大多数反应中都不同，并且很少有共同的必需反应。我们的观察结果表明，大肠杆菌代谢网络对突变的鲁棒性是具有相同表型的网络的典型特征。我们还证明，具有相同表型的网络形成了可以通过单个突变遍历的大集合，并且具有相同表型的不同基因型的单个突变可以产生非常不同的新表型。这意味着代谢网络的进化可塑性和鲁棒性促进了新代谢能力的进化。我们的方法对代谢网络的进化、对突变鲁棒性的理解、抗代谢药物的设计以及代谢工程都具有广泛的意义。
