comparative analysis of dna replication timing reveals conserved large-scale chromosomal architecture比较分析dna复制的时间显示守恒的大型染色体结构.pdfVIP

Comparative Analysis of DNA Replication Timing Reveals Conserved Large-Scale Chromosomal Architecture 1. 2. 3 4,5 1 Eitan Yaffe , Shlomit Farkash-Amar , Andreas Polten , Zohar Yakhini , Amos Tanay *, Itamar Simon2* 1 Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel, 2 Department of Microbiology and Molecular Genetics, the Institute for Medical Research – Israel-Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel, 3 Agilent Technologies, Waldbronn, Germany, 4 Department of Computer Sciences, Technion – Israel Institute of Technology, Haifa, Israel, 5 Agilent Laboratories, Tel-Aviv, Israel 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 nuc