The conflict within: origin, proliferation and persistence of a spontaneously arising selfish mitochondrial genome

Mitochondrial genomes can sustain mutations that are simultaneously detrimental to individual fitness and yet, can proliferate within individuals owing to a replicative advantage. We analysed the fitness effects and population dynamics of a mitochondrial genome containing a novel 499 bp deletion in the cytochrome b(1) (ctb-1) gene (Δctb-1) encoding the cytochrome b of complex III in Caenorhabditis elegans. Δctb-1 reached a high heteroplasmic frequency of 96% in one experimental line during a mutation accumulation experiment and was linked to additional spontaneous mutations in nd5 and tRNA-Asn. The Δctb-1 mutant mitotype imposed a significant fitness cost including a 65% and 52% reduction in productivity and competitive fitness, respectively, relative to individuals bearing wild-type (WT) mitochondria. Deletion-bearing worms were rapidly purged within a few generations when competed against WT mitochondrial DNA (mtDNA) bearing worms in experimental populations. By contrast, the Δctb-1 mitotype was able to persist in large populations comprising heteroplasmic individuals only, although the average intracellular frequency of Δctb-1 exhibited a slow decline owing to competition among individuals bearing different frequencies of the heteroplasmy. Within experimental lines subjected to severe population bottlenecks (n = 1), the relative intracellular frequency of Δctb-1 increased, which is a hallmark of selfish drive. A positive correlation between Δctb-1 and WT mtDNA copy-number suggests a mechanism that increases total mtDNA per se, and does not discern the Δctb-1 mitotype from the WT mtDNA. This study demonstrates the selfish nature of the Δctb-1 mitotype, given its transmission advantage and substantial fitness load for the host, and highlights the importance of population size for the population dynamics of selfish mtDNA. This article is part of the theme issue 'Linking the mitochondrial genotype to phenotype: a complex endeavour'.