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Published on: September 29, 2011
Mitochondrial Genome Instability in W303-SK1 Yeast Cytoplasmic Hybrids
Khoren K Epremyan1, Arteom A Burlaka2, Olga V Markova1
1A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskiye Gory, 1-40, 119234 Moscow, Russia.
Abstract:
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.
Insights
Mitochondrial DNA (mtDNA) suppressivity in yeast is determined by the mtDNA sequence itself, not the nuclear genome. This finding impacts our understanding of how mutant mtDNA variants can outcompete wild-type versions.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Some fungi, like baker's yeast, exhibit biparental inheritance of mitochondrial DNA (mtDNA).
- Mutant mtDNA (rho) with deletions can displace wild-type (rho+) mtDNA, a phenomenon known as suppressivity.
- Offspring of zygotes with rho mtDNA often inherit the mutant variant, influencing cellular function.
Purpose of the Study:
- To investigate the influence of mitochondrial and nuclear genomes on rho mtDNA suppressivity during yeast crosses.
- To determine whether mtDNA sequence or nuclear background dictates the suppressivity of mutant mitochondrial DNA.
Main Methods:
- Comparative analysis of suppressivity in crosses between different yeast strains (SK1 and W303) and rho strains.
- Creation of cytoplasmic hybrids by exchanging mtDNAs between strains.
- Measurement of respiration and growth rates on non-fermentable substrates.
Main Results:
- One rho strain exhibited significantly higher suppressivity when crossed with the SK1 strain compared to the W303 strain.
- mtDNA, not nuclear DNA, was identified as the primary determinant of high suppressivity in specific crosses.
- mtDNA replacement led to reduced respiration and growth rates, and increased loss of functional mtDNA.
Conclusions:
- The suppressivity of mutant mtDNA is predominantly determined by its own sequence, rather than the nuclear genome's context.
- This suggests that mtDNA sequence directly influences its ability to outcompete other mitochondrial DNA variants in heteroplasmic cells.
- Understanding suppressivity mechanisms is crucial for studying mitochondrial genetics and inheritance.
