Mitochondrial Genome Instability in <i>W303-SK1</i> 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 (<i>rho<sup>−</sup>...

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Main Authors: Khoren K. Epremyan, Arteom A. Burlaka, Olga V. Markova, Kseniia V. Galkina, Dmitry A. Knorre
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/13/11/927
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Summary: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 (<i>rho<sup>−</sup></i>), with large deletions in the nucleotide sequence, can displace wild-type (<i>rho<sup>+</sup></i>) mtDNA. Consequently, offspring of zygotes with such <i>rho<sup>−</sup></i> mtDNA predominantly carry the mutant variant. This phenomenon is called suppressivity. In this study, we investigated how the suppressivity of <i>rho<sup>−</sup></i> mtDNA depends on the mitochondrial and nuclear genomes of the <i>rho<sup>+</sup></i> strain during crossing. Comparing two diverged laboratory strains, <i>SK1</i> and <i>W303</i>, we measured suppressivity in crosses with four <i>rho<sup>−</sup></i> strains. One <i>rho<sup>−</sup></i> strain showed significantly higher suppressivity when crossed with <i>SK1</i> than with <i>W303</i>. We then created cytoplasmic hybrids by swapping mtDNAs between these strains. Surprisingly, we found that the mtDNA of the <i>rho<sup>+</sup></i> strain, rather than its nuclear DNA, determines high suppressivity in crosses of <i>SK1 rho<sup>+</sup></i> with the <i>rho<sup>−</sup></i> 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.
ISSN:2079-7737