Deutscher David, Meilijson Isaac, Kupiec Martin, Ruppin Eytan
School of Computer Science, Tel Aviv University, PO Box 39040, Tel Aviv 69978, Israel.
Nat Genet. 2006 Sep;38(9):993-8. doi: 10.1038/ng1856.
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.
遗传稳健性体现了表型在面对可遗传扰动时的稳定性。以往的研究利用全面的单基因和双基因敲除来研究酿酒酵母中的基因必需性和基因对之间的相互作用。在此，我们对酵母代谢网络的通量平衡分析模型进行了计算机模拟多重敲除研究。通过对提供相互功能备份的基因集进行编目，我们识别出多达八个相互作用基因的集合，并对每个基因的“k稳健性”（备份相互作用的深度）进行了表征。我们发现，74%（360个）的代谢基因参与了在标准实验室环境中对生长至关重要的过程，相比之下，之前通过单基因敲除发现只有13%的基因是必需的。研究表明，基因的k稳健性是其生物缓冲能力的可靠指标，并且与基因的环境特异性及其进化保留都相关。
