On the localization of the origin of DNA replication in E. coli

Litwin, S.; Kallenbach, N.R.

Journal of Theoretical Biology 64(4): 747-760


ISSN/ISBN: 0022-5193
PMID: 321880
DOI: 10.1016/0022-5193(77)90273-9
Accession: 068526238

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The process of DNA replication in prokaryotes with a circular chromosome is analyzed in terms of a stochastic model with heterogeneity in the rate of DNA synthesis from cell to cell in a culture, any degree of positive or negative correlation between mother and daughter cells, and drift of the origin and terminus in a chromosome from 1 generation to the next over a specified region or set of points in the chromosome. The model is applied to experimental data on Escherichia 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 a remarkable latitude for drift of the origin from 1 generation to the next, with succeeding rounds capable of initiation at any site within a region of 1/2 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.