Schematic of feedbacks into GRN from MN.

A. Example of the feedback from the MN to the GRN. The TF XylR (coded for by the gene xylR), when activated, binds to and switches on the gene xylA (which codes for the enzyme XylA). XylA catalyzes the metabolic reaction in which metabolite D-xylose is converted into D-xylulose. D-xylose binds to XylR and activates it namely, causes it to bind to its target gene). The two figures in A are representation of the above statements. The table categorizes each type of link involved and gives its physical interpretation. This feedback has the dynamical consequence that excess of D-xylose in the cell is regulated by enhancing its conversion into D-xylulose (through activation of XylR that up-regulates XylA which catalyzes the conversion). B. GRNs with feedbacks from metabolic network. C. Histograms (bin size 20) of potential impact of feedbacks from metabolic network into the respective GRNs of E. coli, (a), and B. subtilis, (b). Note that to avoid clutter we do not introduce separate nodes for a TF and the gene that codes for it. Thus the node representing a TF coding gene does double duty and represents both the genes and the corresponding TF. An arrow from a metabolite node (cyan) to a TF coding gene (pink) does not mean that the metabolite increases the expression of the gene. It means that the metabolite activates the TF coded for by the gene (namely, causes the TF to bind to its target genes and carry out its function—activating or inhibiting transcription of its target gene). However a green/red arrow (+ or −) from a TF coding gene (pink) to another TF coding gene (as in GRN of panel B) means that the former TF activates/inactivates the transcription of the latter gene.