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Abstract
摘要 |
Genome replication, a key physiological process for a living cell, typically relies on intrinsically stochastic initiation by replication origins, causing a variability of replication timing from cell to cell. Over evolution, an organism can control only the propensity of origins to initiate and their position, but it does not eliminate completely this uncertainty. While widely accepted mathematical models of eukaryotic replication as a stochastic process are available, the question of the link between the controllable parameters and the resulting distribution of global replication timing has not been addressed systematically.
Here, we propose a combined analytical and computational approach to this question. Our calculations give a simple way to understand how positions and strengths of many origins lead to a given distribution 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 lead us to 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 (and is hence "fragile"). Conversely, when the completion times 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 two yeast species falls in this extreme-value regime. |
