GC skew and mitochondrial origins of replication.

The comprehensive understanding of mitochondrial genome evolution requires a detailed mechanistic picture of mitogenomic replication. Despite many previous efforts it has remained a non-trivial problem to determine the origins of replication and trace their fate across rearrangements of the gene order even in the small genomes of animal mitochondria. We elaborate here on the observation that the GC skew is correlated with the distance from the replication origins. This effect has been explained as a consequence of the standard model of mitochondrial DNA replication, i.e. the strand displacement model. According to this model chemical damage accumulates proportional to the duration that DNA is exposed in single-stranded form during replication (Dssh) which depends on the relative position with respect to the replication origins. Based on this model we developed a computational method to infer the positions of both the heavy strand and the light strand origin from nucleotide skew data. In a comprehensive survey of deuterostome mitochondria we infer conserved replication origins for the vast majority of vertebrates and cephalochordates. Deviations from the consensus picture are presumably associated with genome rearrangements.