Extend the repressilator idea to a ring of four repressor genes: gene 1 represses gene 2

PHYSICS · Multi-part · Fermi University Physics · Biophysics & Medical Physics · Genetic circuits, regulation and biological information · Genetic circuits, regulation and biological information

Forces, Machines and Signals, Ch Genetic circuits and biological pattern

Problem

Extend the repressilator idea to a ring of four repressor genes: gene 1 represses gene 2, gene 2 represses gene 3, gene 3 represses gene 4, and gene 4 represses gene 1, each obeying the same scaled kinetics x˙i=f(xi−1)−xi\dot x_i = f(x_{i-1}) - x_i. Linearising about the symmetric steady state, each gene's own decay contributes −1-1 on the diagonal and the repression from its neighbour contributes an off-diagonal slope g<0g<0 (with ∣g∣|g| increasing with promoter strength and cooperativity). By the same reasoning used for the ring of three, the eigenvalues of the linearised system are λk=−1+g ωk,ωk=e2πik/4,k=0,1,2,3,\lambda_k = -1 + g\,\omega_k, \qquad \omega_k = e^{2\pi i k/4}, \quad k=0,1,2,3, the fourth roots of unity. ((a)) Evaluate ωk\omega_k for k=0,1,2,3k=0,1,2,3 and give the four eigenvalues λk\lambda_k in terms of gg. ((b)) Identify which eigenvalue(s) can acquire a positive real part as ∣g∣|g| increases from zero, and find the value of ∣g∣|g| at which this first happens. ((c)) State whether the mode that goes unstable first is real or part of a complex-conjugate pair, and use that to decide whether a ring of four repressors is expected to oscillate like the ring of three or to show a toggle-like instability like the ring of two.

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