Nature Genetics
- 38, 993 - 998 (2006)
Published online: 29 August 2006; | doi:10.1038/ng1856
Multiple knockout analysis of genetic robustness in the yeast metabolic networkDavid Deutscher1, Isaac Meilijson2, Martin Kupiec3 & Eytan Ruppin1, 41
School of Computer Science, Tel Aviv University, PO Box 39040, Tel Aviv 69978, Israel. 2
School of Mathematical Sciences, Tel Aviv University, PO Box 39040, Tel Aviv 69978, Israel. 3
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, PO Box 39040, Tel Aviv 69978, Israel. 4
School of Medicine, Tel Aviv University, PO Box 39040, Tel Aviv 69978, Israel.
Correspondence should be addressed to Eytan Ruppin ruppin@post.tau.ac.il 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.
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