Regulation of DNA replication time is crucial for appropriate gene expression

Eukaryotic genomes are replicated in a reproducible temporal order, however, the physiological significance is poorly understood. We compared replication dynamics in divergent yeast species and identified genomic features with conserved replication times. Histone genes were amongst the earliest replicating loci in all species. We delayed the replication of HTA1-HTB1 and discovered that this halved the histone gene expression. Finally, we show that histone and cell cycle genes in general are exempt from dosage compensation mechanisms. Thus we have uncovered one of the first physiological requirements for regulated replication time and demonstrate a direct link between replication time and gene expression. Overall design: Measurement of genome replication time from 6 budding yeast species (Candida glabrata, Naumovozyma castellii, Tetrapisispora blattae, Zygosaccharomyces rouxii, Kluyveromyces lactis, Lachancea kluyveri) and a Saccharomyces cerevisiae strain (triple origin mutant with ARS427.5, ARS428 and ARS429 inactivated). For each strain two samples were analysed: a replicating sample (from S phase) and a non-replicating sample (from G2 phase).