Gabaldón Toni, Peretó Juli, Montero Francisco, Gil Rosario, Latorre Amparo, Moya Andrés
Bioinformatics Department, Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler, 16. 46013 València, Spain.
Philos Trans R Soc Lond B Biol Sci. 2007 Oct 29;362(1486):1751-62. doi: 10.1098/rstb.2007.2067.
By integrating data from comparative genomics and large-scale deletion studies, we previously proposed a minimal gene set comprising 206 protein-coding genes. To evaluate the consistency of the metabolism encoded by such a minimal genome, we have carried out a series of computational analyses. Firstly, the topology of the minimal metabolism was compared with that of the reconstructed networks from natural bacterial genomes. Secondly, the robustness of the metabolic network was evaluated by simulated mutagenesis and, finally, the stoichiometric consistency was assessed by automatically deriving the steady-state solutions from the reaction set. The results indicated that the proposed minimal metabolism presents stoichiometric consistency and that it is organized as a complex power-law network with topological parameters falling within the expected range for a natural metabolism of its size. The robustness analyses revealed that most random mutations do not alter the topology of the network significantly, but do cause significant damage by preventing the synthesis of several compounds or compromising the stoichiometric consistency of the metabolism. The implications that these results have on the origins of metabolic complexity and the theoretical design of an artificial minimal cell are discussed.
通过整合比较基因组学和大规模缺失研究的数据，我们之前提出了一个由206个蛋白质编码基因组成的最小基因集。为了评估由这样一个最小基因组编码的代谢的一致性，我们进行了一系列计算分析。首先，将最小代谢的拓扑结构与从天然细菌基因组重建的网络的拓扑结构进行比较。其次，通过模拟诱变评估代谢网络的稳健性，最后，通过从反应集自动推导稳态解来评估化学计量一致性。结果表明，所提出的最小代谢具有化学计量一致性，并且它被组织成一个复杂的幂律网络，其拓扑参数落在与其大小相当的天然代谢的预期范围内。稳健性分析表明，大多数随机突变不会显著改变网络的拓扑结构，但会通过阻止几种化合物的合成或损害代谢的化学计量一致性而造成重大损害。讨论了这些结果对代谢复杂性起源和人工最小细胞理论设计的影响。
