The maintenance of self-replicating plasmids in Saccharomyces cerevisiae: mathematical modelling, computer...

A distributive model has been constructed to describe the maintenance of the native 2 microns and 2 micron-based plasmids in the yeast Saccharomyces cerevisiae. This model includes elements which represent the influence of selection, segregation, replication and amplification on plasmid stability. A computer program has been written in TURBO PASCAL to implement the model and a number of simulation experiments have been carried out. These simulations permitted the choice of a form of the model which is compatible with the available experimental evidence. The form chosen involves an amplification system in which the RAF gene product binds to the Rep1/Rep2 dimer to prevent the latter acting to repress the activity of the FLP gene. At the same time an upper limit (or 'ceiling') was imposed on the number of plasmid molecules able to replicate. Maternal bias was accommodated by 'tagging' a small proportion of molecules for inheritance by the mother nucleus and these tags being removed (or 'cleared') by the Rep1/Rep2 dimers. This final form of the model makes specific predictions about the stability of 2 microns and YEp plasmids in yeast populations and about the distribution of plasmid copy number between cells in such populations. The predictions on stability have been subjected to experimental test and results provide good support for the model.