  Genome replication, a key process for a cell, relies on stochastic initiation
by replication origins, causing a variability of replication timing from cell
to cell. While stochastic models of eukaryotic replication are widely
available, the link between the key parameters and overall replication timing
has not been addressed systematically.We use a combined analytical and
computational approach to calculate how positions and strength of many origins
lead to a given cell-to-cell variability of total duration of the replication
of a large region, a chromosome or the entire genome.Specifically, the total
replication timing can be framed as an extreme-value problem, since it is due
to the last region that replicates in each cell. Our calculations identify two
regimes based on the spread between characteristic completion times of all
inter-origin regions of a genome. For widely different completion times, timing
is set by the single specific region that is typically the last to replicate in
all cells. Conversely, when the completion time of all regions are
comparable,an extreme-value estimate shows that the cell-to-cell variability of
genome replication timing has universal properties. Comparison with available
data shows that the replication program of three yeast species falls in this
extreme-value regime.
