From DNA sequence analysis to modeling replication in the human genome

TL;DR

This study analyzes nucleotide strand asymmetries in human chromosomes, proposing a replication model that explains observed skew profiles and identifies potential replication origin pairs with specific spacing.

Contribution

It introduces a model of replication origins and terminations that accounts for skew profiles and predicts replication origin pairs in the human genome.

Findings

Sharp upward jumps in (TA+GC) skew at replication origins

Identification of 287 pairs of putative replication origins

Replication origin spacing of approximately 1-2 Mbp

Abstract

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 approximately 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.