title: Comparative analysis of DNA replication timing reveals conserved large-scale chromosomal architecture.
abstract: Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes, yet the importance of this aspect of genome organization is unclear. Here we show that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged. This conservation is both tissue-specific and independent of the genomic G+C content conservation. Moreover, we show that time of replication is globally conserved despite numerous large-scale genome rearrangements. We systematically identify rearrangement fusion points and demonstrate that replication time can be locally diverged at these loci. Conversely, rearrangements are shown to be correlated with early replication and physical chromosomal proximity. These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome.
authors.affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Eitan
authors.initials: E
authors.lastname: Yaffe
authors.forename: Shlomit
authors.initials: S
authors.lastname: Farkash-Amar
authors.forename: Andreas
authors.initials: A
authors.lastname: Polten
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Amos
authors.initials: A
authors.lastname: Tanay
authors.forename: Itamar
authors.initials: I
authors.lastname: Simon
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D042522:DNA Replication Timing; D019143:Evolution, Molecular; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice