Rosenfeld R. Grover N B.
Control of mini-R1 plasmid replication: A computer
simulation, Plasmid 29(2) :94-116, 1993.
Abstract
A molecular model for the control of plasmid R1 replication has been proposed
by Nordstrom, Molin and Light (Plasmid 12, 71-90, 1984), involving three
genes: repA, copA, copB. RepA codes for a polypeptide whose synthesis is
required for initiation; relication is controlled by regulating this
synthesis. CopA encodes a small, unstable, untranslated RNA molecule that
inhibits translation of the repA message between whereas copB produced a
protein that inhibits transcription from the repA promoter. We have recast
this model into precise mathematical terms and tested it by computer
simulation of a synchronous culture in steady-state balanced
growth, composed of individual Escherichia coli cells harboring the small,
unstable derivative, mini-RI. All single-cell steady-state distributions
obtained are independent of initial conditions, and the average values of
various plasmid-related variables are similar to those measured
experimentally. The relationship between the number of replication events per
cell and the copy numbers at birth, as predicted by the model, mitigates
against a sensitive correction mechanism for cells born with other than
average copy number and is much closer quantitatively to a nonresponse
system, although there is a weak dependence on copy number. The effect of the
convergnt transcription initiated at the repA and copB promoters on the
expression of the copA gene is found to contribute little to the sability of
mini-R1 replicons under steady-state growth conditions or to their potential
for survival following infection. In fact, the role of the entire CopB
control loop is shown to be quite minor, both in steady state and after
infection. It is pointed out that genetic manipulations are far more easily
performed in silico than in vivo but that results of the
kind presented here are very often possible only when simulating individaul
cells.
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