The evolution of the temporal program of genome replication

Abstract

Comparative analyses of temporal programs of genome replication revealed either a nearly complete conservation between closely related species or a comprehensive reprogramming between distantly related species. Therefore, many important questions on the evolutionary remodeling of replication timing programs remain unanswered. To address this issue, we generated genome-wide replication timing profiles for ten yeast species from the genus Lachancea, covering a continuous evolutionary range from closely related to more divergent species. The comparative analysis of these profiles revealed that the replication program linearly evolves with increasing evolutionary divergence between these species. We found that the evolution of the timing program mainly results from a high evolutionary turnover rate of the cohort of active replication origins. We detected about one thousand evolutionary events of losses of active replication origins and gains of newborn origins since the species diverged from their last common ancestor about 80 million years ago. We show that the relocation of active replication origins is independent from synteny breakpoints, suggesting that chromosome rearrangements did not drive the evolution of the replication programs.Rather, origin gains and losses are linked both in space, along chromosomes, and in time, along the same branches of the phylogenetic tree. New origins continuously arise with on average low to medium firing efficiencies and increase in efficiency and earliness as they evolutionarily age. Yet, a subset of newborn origins emerges with high firing efficiency and origin losses occur concomitantly to their emergence and preferentially in their direct chromosomal vicinity. These key findings on the evolutionary birth, death and conservation of active replication origins provide the first description of how the temporal program of genome replication has evolved in eukaryotes.

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints

“…Thus, this model would explain why replication origins appear to be under purifying selection on a short time-scale but not conserved over the long term. A similar model has recently been proposed to explain the evolution of yeast replication origins (Agier et al 2017). This peculiar temporal conservation pattern is not specific to replication origins: for many functional elements located in non-coding regions, signatures of selection are better revealed by analysis of polymorphisms than by inter-species comparisons (di Iulio et al 2018).…”

“…Alternatively, the observation that replication origin density is high in early replication domains and low in late replicating ones could lead to another explanation. Indeed, if origin losses are replaced by origin gains in close proximity, as suggested in a recent study in yeast (Agier et al 2017), the origin density of replication domains -and hence, their replication timing -would be maintained despite the rapid turnover of origins.…”