The process of DNA replication in procaryotes with a circular chromosome is analyzed in terms of a stochastic model including the following features: (1) heterogeneity in the rate of DNA synthesis from cell to cell in a culture, (2) any degree of positive or negative correlation between mother and daughter cells and (3) drift of the origin and terminus in a chromosome from one generation to the next over a specified region or set of points in the chromosome. The model is applied to experimental data on E. coli cells in balanced growth, assuming the bidirectional replication process can be simulated by independent unidirectional processes along each arm. Comparison of calculated recovery profiles for label in a density pulse experiment reveals that there is remarkable latitude for drift of the origin from one generation to the next, with succeeding rounds capable of initiation at any site within a region of one half the total chromosomal length. The marker frequencies of genes at different positions on the chromosome measured by "equilibrium" assays similarly can be reconciled with unidirectional or bidirectional processes with a wandering origin. If as is suggested by results from kinetic experiments on populations with aligned chromosomes replication is bidirectional with a unique fixed site of origin, the results of the label recovery experiments are inconsistent with the available evidence for heterogeneity in replication times and growth rates.
ASJC Scopus subject areas
- Statistics and Probability
- Modeling and Simulation
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)
- Agricultural and Biological Sciences(all)
- Applied Mathematics