DNA replication and the nucleation-and-growth model. (A) When water freezes, for example, nucleation sites grow to fill the entire volume (only one spatial dimension is shown as a function of time increasing upwards). (B) In cells, the last coalescent event at time t between the growing replication bubbles determines the duration of DNA replication. The distribution of ρ(t) depends on the “nucleation” rate I(x,t) as well as the growth rate v. (C) If origin firing is randomly distributed in space and time, occasional large gaps will greatly delay the completion of replication. (D) Yang and Bechhoefer have shown rigorously how the optimal timing can be achieved so all the bubbles finish at the same time . Even with a random distribution of origin firing in space, if the probability of origin firing increases with time, large gaps are efficiently replicated. Because large gaps are rare, this increased origin firing late in the replication phase does not significantly increase the total number of origins fired.