From DNA Sequence Analysis to Modeling Replication in the Human Genome

We explore the large-scale behavior of nucleotide compositional strand asymmetries along human chromosomes. As we observe for 7 of 9 origins of replication experimentally identified so far, the (TA+GC) skew displays rather sharp upward jumps, with a linear decreasing profile in between two successive jumps. We present a model of replication with well positioned replication origins and random terminations that accounts for the observed characteristic serrated skew profiles. We succeed in identifying 287 pairs of putative adjacent replication origins with an origin spacing ∼1–2  Mbp that are likely to correspond to replication foci observed in interphase nuclei and recognized as stable structures that persist throughout subsequent cell generations.