FIGURE 3.

Schematic models of co-evolution between selfish mtDNA and the nuclear genome. Yeast cell lines with various mitochondrial mutation rates are constructed using different mutant forms of the mitochondrial DNA replication protein Mip1 and mismatch repair protein Msh1. Parallel sexual cultures are then set up to evolve in different population sizes. Outcrossed sex exposes mitochondrial genomes to competition and allows selfish mtDNA to spread despite organismal fitness costs. In addition, other deleterious mutations (shown as blue circles) have the opportunity to hitchhike with the selfish mtDNA when it is spreading through the population. When the frequency of deleterious mutations in mtDNA is increasing in the population, it results in a fitness valley. Subsequently, compensatory mutations in the nuclear genome will be selected to restore the host fitness unless the fitness valley is too deep to be recovered. This system allows us to assay the influence of different evolutionary parameters (i.e., mutation rate, population size and outcrossing frequency) on the co-evolution patterns between mitochondrial and nuclear genomes.