Reverse your mtDNA control region and you’ll reverse your mutation bias.

The Inversion of the Control Region in Three Mitogenomes Provides Further Evidence for an Asymmetric Model of Vertebrate mtDNA Replication, PlosOne 2014

As many of you are probably aware of there is an ongoing debate regarding the mechanism of mitochondrial DNA (mtDNA) replication (see for instance Holt and Reyes, 2012). The models were summarized well in a recent paper from Fonseca et al. in PlosOne 2014.

 

Fonseca MM et al. PlosOne 2014

They analyzed the base composition of the mtDNA protein-coding genes (2500 mtDNAs) and found a clear bias, which correlated with the direction of the control region. Based on this they concluded that the strand-displacement model (SDM) or the ribonucleotides-incorporation throughout the lagging strand model (RITOLS) is likely to be the replication mechanism instead of the strand-coupled model (SCM).

Of course one can always hypothesize that the SCM is specific for cell cultures (as in the original paper describing this model) or is tissue specific. However, from the evolutionary point of view the strand-displacement model seems to be the more important one. Whether the single-strand DNA is covered by mtSSB or RNA remains to be seen.