Different groups of metabolic genes cluster around early and late firing origins of replication in budding yeast.

DNA replication is a fundamental process that is tightly regulated during the cell cycle. In budding yeast it starts from multiple origins of replication and proceeds in a timely fashion according to a reproducible temporal program until the entire DNA is replicated exactly once per cell cycle. In this program an origin seems to have an inherent firing probability at a specific time in S-phase that is conserved over the population. However, what exactly determines the origin initiation time remains obscure. In this work, we analyze the gene content that clusters around replication origins following the assumption that inherent origin properties that determine staggered initiation times could potentially be mirrored in the close origin proximity. We perform a Gene Ontology term enrichment test and find that metabolic genes are significantly over-represented in the regions that are close to the starting points of DNA replication. Furthermore, functional analysis also reveals that catabolic genes cluster around early firing origins, whereas anabolic genes can rather be found in the proximity of late firing origins of replication. We speculate that, in budding yeast, gene function around replication origins correlates with their intrinsic probability to initiate DNA replication at a given point in S-phase.