A nonlinear technique for the analysis of plasmid instability in micro-organisms.

A nonlinear technique to calculate parameters for segregational instability and differences in cellular growth-rate for plasmid-bearing micro-organisms growing in batch or continuous culture is presented. This method is compared with an approximate technique based upon linear regression. The accuracy and sensitivity of the results are evaluated by use of simulated data and biological data taken from experiments with Pseudomonas aeruginosa(pGSS15) and Escherichia coli(pHSG415). It is demonstrated that the nonlinear analysis gives results which are significantly more accurate and which show much better agreement with the data. Consequently, the new analysis leads to quite different conclusions with regard to the nature of the instability of the plasmid-bearing strain. This method offers an opportunity to study the genetic and physiological aspects of plasmid instability and so aid the design and optimization of cloning vectors.