Structural similarities between a mitochondrially encoded polypeptide and a family of prokaryotic respiratory toxins involved in plasmid maintenance suggest a novel mechanism for the evolutionary maintenance of mitochondrial DNA.

Subunit 8 of mitochondrial ATP synthase (A8), a mitochondrially encoded polypeptide, has no known homologue in any prokaryotic or plastid ATP synthase, suggesting that it has been recruited to its present role in the enzyme from an extraneous source. The polypeptide is poorly conserved at the primary sequence level, but shows a well-conserved hydropathy profile. The hydropathy profiles of A8 from diverse taxa were compared with those of the hok family of prokaryotic respiratory toxins, some of whose members are involved in plasmid maintenance, through postsegregational killing of cells that lose the plasmid at cell division. Such comparisons revealed a highly significant degree of similarity, suggesting a functional relationship. Based on these findings, it is proposed that A8 evolved from a hok-like protein, whose original role was the maintenance of an extrachromosomal replicon in the endosymbiont ancestor of mitochondria. An aggressive mechanism for the evolutionary maintenance of mitochondrial DNA overcomes many of the failings of traditional explanations for its retention as a separate genome.