Multiple knockout analysis of genetic robustness in the yeast metabolic network
Multiple knockout analysis of genetic robustness in the yeast metabolic network
复制标题
DOI：
10.1038/ng1856
复制
发表时间：
2006-09-01
期刊：
影响因子：
30.8
通讯作者：
Ruppin, Eytan
中科院分区：
文献类型：
--
作者：
Deutscher, David;Meilijson, Isaac;Ruppin, Eytan
遗传稳健性表征了面对遗传扰动时表型的稳定性。以前的研究已经使用全面的单基因和双基因敲除来研究酵母中基因的必要性和成对的基因相互作用。在这里，我们对酵母代谢网络的通量平衡分析模型进行了硅多重敲除研究。编目提供相互功能备份的基因集，我们确定了多达八个相互作用的基因集，并表征了每个基因的“k鲁棒性”（备份相互作用的深度）。我们发现74%（360）的代谢基因参与了在标准实验室环境中生长所必需的过程，相比之下，以前使用单敲除方法发现只有13%的代谢基因是必需的。基因的k稳健性被证明是其生物缓冲能力的可靠指标，并且与基因的环境特异性和它们的进化保留有关。
Genetic robustness characterizes the constancy of the phenotype in face of heritable perturbations. Previous investigations have used comprehensive single and double gene knockouts to study gene essentiality and pairwise gene interactions in the yeast Saccharomyces cerevisiae. Here we conduct an in silico multiple knockout investigation of a flux balance analysis model of the yeast's metabolic network. Cataloging gene sets that provide mutual functional backup, we identify sets of up to eight interacting genes and characterize the 'k robustness' ( the depth of backup interactions) of each gene. We find that 74% ( 360) of the metabolic genes participate in processes that are essential to growth in a standard laboratory environment, compared with only 13% previously found to be essential using single knockouts. The genes' k robustness is shown to be a solid indicator of their biological buffering capacity and is correlated with both the genes' environmental specificity and their evolutionary retention.