High nucleotide skew palindromic DNA sequences function as replication origins due to their unzipping propensity

Locations of DNA replication initiation in prokaryotes, called "origins of replication", are well-characterized. However, a mechanistic understanding of the sequence-dependence of the local unzipping of double-stranded DNA, the first step towards replication initiation, is lacking. Here, utilizing a Markov chain model that was created to address the directional nature of DNA unzipping and replication, we model the sequence dependence of local melting of double-stranded linear DNA segments. We show that generalized palindromic sequences with high nucleotide skews have a low kinetic barrier for local melting near melting temperatures. This allows for such sequences to function as replication origins. We support our claim with evidence for high-skew palindromic sequences within the replication origins of mitochondrial DNA, bacteria, archaea and plasmids.