 | Figure 2
Nature Biotechnology
22, 86 - 92 (2003)
Published online: 30 November 2003; | doi:10.1038/nbt918
Principles of transcriptional control in the metabolic network of Saccharomyces cerevisiaeJan Ihmels, Ronen Levy
& Naama Barkai | | | | Figure 2. Coexpressed enzymes often catalyze a linear chain of reactions.
(a) Coregulation between enzymes associated with central metabolic pathways. Each branch corresponds to several enzymes whose identity is given on our web page. In the cases shown, only one of the branches downstream of the junction point is coregulated with upstream genes. (b) Coregulation pattern in three-point junctions. All junctions corresponding to metabolites that participate in exactly three reactions (according to the KEGG database) were identified and the correlations between the genes associated with each such junction were calculated. The junctions were grouped according to the directionality of the reactions, as shown. Divergent junctions, which allow the flow of metabolites in two alternative directions, predominantly show a linear coregulation pattern, where one of the emanating reaction is correlated with the incoming reaction (linear regulatory pattern) or the two alternative outgoing reactions are correlated in a context-dependent manner with a distinct isozyme catalyzing the incoming reaction (linear switch). By contrast, the linear regulatory pattern is significantly less abundant in convergent junctions, where the outgoing flow follows a unique direction, and in conflicting junctions that do not support metabolic flow. Most of the reversible junctions comply with linear regulatory patterns. Indeed, similar to divergent junctions, reversible junctions allow metabolites to flow in two alternative directions. Reactions were counted as coexpressed if at least two of the associated genes were significantly correlated (correlation coefficient >0.25). As a random control, we randomized the identity of all metabolic genes and repeated the analysis. (c) The connectivity of a given metabolite was defined as the number of reactions connecting it to other metabolites. Shown are the distributions of connectivity between metabolites in an unrestricted network ( ) and in a network where only correlated reactions are considered ( ). In accordance with previous results25, the connectivity distribution between metabolites follows a power law (log-log plot). In contrast, when coexpression is used as a criterion to distinguish functional links, the connectivity distribution becomes exponential (log-linear plot). We verified that neither the functional exponential form nor the range of the distribution depend strongly on the correlation threshold used (see authors' website).
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