| 1. |
- Barré, Benjamin P., et al.
(författare)
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Intragenic repeat expansion in the cell wall protein gene HPF1 controls yeast chronological aging
- 2020
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 30:5, s. 697-710
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Tidskriftsartikel (refereegranskat)abstract
- Aging varies among individuals due to both genetics and environment, but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct quantitative trait loci (QTLs) that control chronological life span (CLS) in calorie-rich and calorie-restricted environments and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes but through different genetic variants. We tracked the two major QTLs to the cell wall glycoprotein genes FLO11 and HPF1. We found that massive expansion of intragenic tandem repeats within the N-terminal domain of HPF1 was sufficient to cause pronounced life span shortening. Life span impairment by HPF1 was buffered by rapamycin but not by calorie restriction. The HPF1 repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation altered methionine, lipid, and purine metabolism, and inhibited quiescence, which explains the life span shortening. We conclude that fast-evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular lifestyle and longevity.
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| 2. |
- De Chiara, Matteo, et al.
(författare)
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Domestication reprogrammed the budding yeast life cycle
- 2022
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X .- 2397-334X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Domestication of plants and animals is the foundation for feeding the world human population but can profoundly alter the biology of the domesticated species. Here we investigated the effect of domestication on one of our prime model organisms, the yeast Saccharomyces cerevisiae, at a species-wide level. We tracked the capacity for sexual and asexual reproduction and the chronological life span across a global collection of 1,011 genome-sequenced yeast isolates and found a remarkable dichotomy between domesticated and wild strains. Domestication had systematically enhanced fermentative and reduced respiratory asexual growth, altered the tolerance to many stresses and abolished or impaired the sexual life cycle. The chronological life span remained largely unaffected by domestication and was instead dictated by clade-specific evolution. We traced the genetic origins of the yeast domestication syndrome using genome-wide association analysis and genetic engineering and disclosed causative effects of aneuploidy, gene presence/absence variations, copy number variations and single-nucleotide polymorphisms. Overall, we propose domestication to be the most dramatic event in budding yeast evolution, raising questions about how much domestication has distorted our understanding of the natural biology of this key model species.
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| 3. |
- Mozzachiodi, Simone, et al.
(författare)
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Aborting meiosis overcomes hybrid sterility
- 2020
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Hybrids between species or diverged lineages contain fundamentally novel genetic combinations but an impaired meiosis often makes them evolutionary dead ends. Here, we explored to what extent and how an aborted meiosis followed by a return-to-growth (RTG) promotes recombination across a panel of 20 yeast diploid backgrounds with different genomic structures and levels of sterility. Genome analyses of 284 clones revealed that RTG promoted recombination and generated extensive regions of loss-ofheterozygosity in sterile hybrids with either a defective meiosis or a heavily rearranged karyotype, whereas RTG recombination was reduced by high sequence divergence between parental subgenomes. The RTG recombination preferentially occurred in regions with local sequence homology and in meiotic recombination hotspots. The loss-of-heterozygosity had a profound impact on sexual and asexual fitness, and enabled genetic mapping of phenotypic differences in sterile lineages where linkage or association analyses failed. We propose that RTG gives sterile hybrids access to a natural route for genome recombination and adaptation.
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| 4. |
- Stenberg, Simon, et al.
(författare)
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Control of mitochondrial superoxide production includes programmed mtDNA deletion and restoration
- 2020
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Deletion of mitochondrial DNA in eukaryotes is mainly attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that the regulatory circuitry underlying this editing critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. Our results may therefore be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.One-Sentence SummaryGenetically controlled editing of mitochondrial DNA is an integral part of the yeast’s defenses against oxidative damage.
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| 5. |
- Stenberg, Simon, et al.
(författare)
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Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation
- 2022
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Ingår i: eLife. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.
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| 6. |
- Stenberg, Simon, et al.
(författare)
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Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation.
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.
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| 7. |
- Tellini, Nicolo, et al.
(författare)
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Ancient and recent origins of shared polymorphisms in yeast
- 2024
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Ingår i: NATURE ECOLOGY & EVOLUTION. - 2397-334X. ; 8, s. 761-776
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Tidskriftsartikel (refereegranskat)abstract
- Shared genetic polymorphisms between populations and species can be ascribed to ancestral variation or to more recent gene flow. Here, we mapped shared polymorphisms in Saccharomyces cerevisiae and its sister species Saccharomyces paradoxus, which diverged 4-6 million years ago. We used a dense map of single-nucleotide diagnostic markers (mean distance 15.6 base pairs) in 1,673 sequenced S. cerevisiae isolates to catalogue 3,852 sequence blocks (>= 5 consecutive markers) introgressed from S. paradoxus, with most being recent and clade-specific. The highly diverged wild Chinese S. cerevisiae lineages were depleted of introgressed blocks but retained an excess of individual ancestral polymorphisms derived from incomplete lineage sorting, perhaps due to less dramatic population bottlenecks. In the non-Chinese S. cerevisiae lineages, we inferred major hybridization events and detected cases of overlapping introgressed blocks across distinct clades due to either shared histories or convergent evolution. We experimentally engineered, in otherwise isogenic backgrounds, the introgressed PAD1-FDC1 gene pair that independently arose in two S. cerevisiae clades and revealed that it increases resistance against diverse antifungal drugs. Overall, our study retraces the histories of divergence and secondary contacts across S. cerevisiae and S. paradoxus populations and unveils a functional outcome. Analysis of 1,673 sequenced Saccharomyces cerevisiae isolates identifies 3,852 sequence blocks introgressed from Saccharomyces paradoxus, most of which are recent and clade-specific. By contrast, divergent Chinese strains of S. cerevisiae show little evidence of introgression but do share ancient polymorphisms with S. paradoxus due to incomplete lineage sorting.
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