Mitochondrial Genome Instability in W303-SK1 Yeast Cytoplasmic Hybrids

Unlike most animals, some fungi, including baker's yeast, inherit mitochondrial DNA (mtDNA) from both parents. When haploid yeast cells fuse, they form a heteroplasmic zygote, whose offspring retain one or the other variant of mtDNA. Meanwhile, some mutant mtDNA (rho), with large deletions in the nucleotide sequence, can displace wild-type (rho) mtDNA. Consequently, offspring of zygotes with such rho mtDNA predominantly carry the mutant variant. This phenomenon is called suppressivity. In this study, we investigated how the suppressivity of rho mtDNA depends on the mitochondrial and nuclear genomes of the rho strain during crossing. Comparing two diverged laboratory strains, SK1 and W303, we measured suppressivity in crosses with four rho strains. One rho strain showed significantly higher suppressivity when crossed with SK1 than with W303. We then created cytoplasmic hybrids by swapping mtDNAs between these strains. Surprisingly, we found that the mtDNA of the rho strain, rather than its nuclear DNA, determines high suppressivity in crosses of SK1 rho with the rho strain. Additionally, mtDNA replacement reduced respiration rate and growth rate on non-fermentable substrates while increasing the likelihood of functional mtDNA loss. Our data demonstrate that a mutant mtDNA variant's ability to displace another mitochondrial DNA variant in a heteroplasmic cell depends more on mtDNA sequences than on the biochemical and structural context created by the nuclear genome background.