Mitochondrial Genome Instability in 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 (), with large deletions in the nucleotide sequence, can displace wild-type () mtDNA. Consequently, offspring of zygotes with such mtDNA predominantly carry the mutant variant. This phenomenon is called suppressivity. In this study, we investigated how the suppressivity of mtDNA depends on the mitochondrial and nuclear genomes of the strain during crossing. Comparing two diverged laboratory strains, and , we measured suppressivity in crosses with four strains. One strain showed significantly higher suppressivity when crossed with than with . We then created cytoplasmic hybrids by swapping mtDNAs between these strains. Surprisingly, we found that the mtDNA of the strain, rather than its nuclear DNA, determines high suppressivity in crosses of with the 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.