Volume 91, Issue 8, Pages (October 2006)

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Volume 91, Issue 8, Pages 2833-2843 (October 2006) In Silico Evolved lac Operons Exhibit Bistability for Artificial Inducers, but Not for Lactose  M.J.A. van Hoek, P. Hogeweg  Biophysical Journal  Volume 91, Issue 8, Pages 2833-2843 (October 2006) DOI: 10.1529/biophysj.105.077420 Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 1 A screen-shot of the grid. (A) Glucose concentration. (B) Lactose concentration. (C) The cells on the grid. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 2 (A) The initial promoter function of every simulation. (B) Two corresponding bifurcation diagrams, for maximal cAMP, i.e., low glucose (solid line) and minimal cAMP, i.e., high glucose (dashed line). For the bifurcation diagram at high-cAMP, low-glucose concentration, a growth rate of μ=0/min is used, while for the bifurcation diagram at low-cAMP, high-glucose, a growth rate of μ=0.01/min is used. Bifurcation diagrams, however, are very similar for different growth rates, because we took γL=γA ≫μ. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 3 (A) Population average of the cusp parameter λ(Cmax), i.e., low glucose, (solid line) and λ(Cmin), i.e., high glucose (dotted line). (B) Population average of the cAMP concentration at which the cusp bifurcation occurs. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 4 (A) The promoter function of the last common ancestor with cost of 3%. All evolved promoter functions are only plotted over the cAMP and allolactose concentration the bacterium experiences, which depend on the promoter function itself. (B) The experimentally measured promoter function (4). Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 5 Two bifurcation diagrams of the promoter function of Fig. 4 A, using lactose (A) or IPTG (B) as inducer. The solid lines represent maximal cAMP concentration, and the dashed lines minimal cAMP concentration. The same growth rates were used as in Fig. 2. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 6 Phase diagram corresponding with the promoter function of Fig. 4 A. For this picture we used a growth rate of μ=0.01/min. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 7 Results of evolution with high cost for promoter activity. (A) Population average of the cusp parameter λ(Cmax) (solid line) and λ(Cmin) (dotted line). (B) Population average of the cAMP concentration at which the cusp bifurcation occurs. (C) Histogram of the number of visits of the promoter function shown in Fig. 7 D in cAMP-allolactose space. (D) The promoter function of the last common ancestor. (E) The bifurcation diagram, corresponding to the promoter function in Fig. 7 D, when growing on lactose, for maximal-cAMP, low-glucose (solid line) and minimal-cAMP, high-glucose (dashed line). Again the same growth rates were used as in Fig. 2. (F) Bifurcation diagrams using IPTG as inducer. Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 8 (A) The promoter function of one of the two most competitive last common ancestors. (B) Population average of the cusp parameter λ(Cmax) (solid line) and λ(Cmin) (dashed line). Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions

Figure 9 Dynamics of Lext, M, and P during a shift from a lactose-poor to a lactose-rich environment. The different lines correspond to different promoter functions, which are only different in one parameter, which determines PA(0, C). Biophysical Journal 2006 91, 2833-2843DOI: (10.1529/biophysj.105.077420) Copyright © 2006 The Biophysical Society Terms and Conditions