The Blavatnik School of Computer Sciences, Faculty of Life Sciences, Ramat Aviv, Israel.
PLoS Comput Biol. 2010 Feb 26;6(2):e1000690. doi: 10.1371/journal.pcbi.1000690.
The evolutionary origins of genetic robustness are still under debate: it may arise as a consequence of requirements imposed by varying environmental conditions, due to intrinsic factors such as metabolic requirements, or directly due to an adaptive selection in favor of genes that allow a species to endure genetic perturbations. Stratifying the individual effects of each origin requires one to study the pertaining evolutionary forces across many species under diverse conditions. Here we conduct the first large-scale computational study charting the level of robustness of metabolic networks of hundreds of bacterial species across many simulated growth environments. We provide evidence that variations among species in their level of robustness reflect ecological adaptations. We decouple metabolic robustness into two components and quantify the extents of each: the first, environmental-dependent, is responsible for at least 20% of the non-essential reactions and its extent is associated with the species' lifestyle (specialized/generalist); the second, environmental-independent, is associated (correlation = approximately 0.6) with the intrinsic metabolic capacities of a species-higher robustness is observed in fast growers or in organisms with an extensive production of secondary metabolites. Finally, we identify reactions that are uniquely susceptible to perturbations in human pathogens, potentially serving as novel drug-targets.
它可能是由于环境条件变化所带来的要求而产生的，也可能是由于代谢需求等内在因素，或者是由于有利于使物种能够耐受遗传扰动的基因的适应性选择而直接产生的。对每种起源的个体效应进行分层，需要在多种条件下对许多物种的相关进化力量进行研究。在这里，我们进行了首次大规模的计算研究，绘制了数百种细菌物种在许多模拟生长环境中的代谢网络鲁棒性水平。我们提供的证据表明，物种之间在鲁棒性水平上的差异反映了生态适应。我们将代谢鲁棒性分解为两个组成部分，并量化了每个组成部分的程度：第一个是环境依赖的，负责至少 20%的非必需反应，其程度与物种的生活方式（专业化/通用型）有关；第二个是环境独立的，与物种的内在代谢能力有关（相关性约为 0.6）——在快速生长的生物或具有广泛次生代谢产物生产的生物中观察到更高的鲁棒性。最后，我们确定了人类病原体中易受干扰的反应，这些反应可能成为新的药物靶点。
