| 1. |
- Gjuvsland, Arne B, et al.
(författare)
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Disentangling genetic and epigenetic determinants of ultrafast adaptation.
- 2016
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Ingår i: Molecular systems biology. - : EMBO. - 1744-4292. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- A major rationale for the advocacy of epigenetically mediated adaptive responses is that they facilitate faster adaptation to environmental challenges. This motivated us to develop a theoretical-experimental framework for disclosing the presence of such adaptation-speeding mechanisms in an experimental evolution setting circumventing the need for pursuing costly mutation-accumulation experiments. To this end, we exposed clonal populations of budding yeast to a whole range of stressors. By growth phenotyping, we found that almost complete adaptation to arsenic emerged after a few mitotic cell divisions without involving any phenotypic plasticity. Causative mutations were identified by deep sequencing of the arsenic-adapted populations and reconstructed for validation. Mutation effects on growth phenotypes, and the associated mutational target sizes were quantified and embedded in data-driven individual-based evolutionary population models. We found that the experimentally observed homogeneity of adaptation speed and heterogeneity of molecular solutions could only be accounted for if the mutation rate had been near estimates of the basal mutation rate. The ultrafast adaptation could be fully explained by extensive positive pleiotropy such that all beneficial mutations dramatically enhanced multiple fitness components in concert. As our approach can be exploited across a range of model organisms exposed to a variety of environmental challenges, it may be used for determining the importance of epigenetic adaptation-speeding mechanisms in general.
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| 2. |
- Gjuvsland, Arne B., et al.
(författare)
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Statistical epistasis is a generic feature of gene regulatory networks
- 2007
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 175:1, s. 411-420
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Tidskriftsartikel (refereegranskat)abstract
- Functional dependencies between genes are a defining characteristic of gene networks underlying quantitative traits. However, recent studies show that the proportion of the genetic variation that can be attributed to statistical epistasis varies from almost zero to very high. It is thus of fundamental as well as instrumental importance to better understand whether different functional dependency patterns among polymorphic genes give rise to distinct statistical interaction patterns or not. Here we address this issue by combining a quantitative genetic model approach with genotype-phenotype models capable of translating allelic variation and regulatory principles into phenotypic variation at the level of gene expression. We show that gene regulatory networks with and without feedback motifs can exhibit a wide range of possible statistical genetic architectures with regard to both type of effect explaining phenotypic variance and number of apparent loci underlying the observed phenotypic effect. Although all motifs are capable of harboring significant interactions, positive feedback gives rise to higher amounts and more types of statistical epistasis. The results also suggest that the inclusion of statistical interaction terms in genetic models will increase the chance to detect additional QTL as well as functional dependencies between genetic loci over a broad range of regulatory regimes. This article illustrates how statistical genetic methods can fruitfully be combined with nonlinear systems dynamics to elucidate biological issues beyond reach of each methodology in isolation.
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| 3. |
- Ibstedt, Sebastian, 1983, et al.
(författare)
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Concerted Evolution of Life Stage Performances Signals Recent Selection on Yeast Nitrogen Use.
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 32:1, s. 153-161
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Tidskriftsartikel (refereegranskat)abstract
- Exposing natural selection driving phenotypic and genotypic adaptive differentiation is an extraordinary challenge. Given that an organism's life stages are exposed to the same environmental variations, we reasoned that fitness components, such as the lag, rate, and efficiency of growth, directly reflecting performance in these life stages, should often be selected in concert. We therefore conjectured that correlations between fitness components over natural isolates, in a particular environmental context, would constitute a robust signal of recent selection. Critically, this test for selection requires fitness components to be determined by different genetic loci. To explore our conjecture, we exhaustively evaluated the lag, rate, and efficiency of asexual population growth of natural isolates of the model yeast Saccharomyces cerevisiae in a large variety of nitrogen-limited environments. Overall, fitness components were well correlated under nitrogen restriction. Yeast isolates were further crossed in all pairwise combinations and coinheritance of each fitness component and genetic markers were traced. Trait variations tended to map to quantitative trait loci (QTL) that were private to a single fitness component. We further traced QTLs down to single-nucleotide resolution and uncovered loss-of-function mutations in RIM15, PUT4, DAL1, and DAL4 as the genetic basis for nitrogen source use variations. Effects of SNPs were unique for a single fitness component, strongly arguing against pleiotropy between lag, rate, and efficiency of reproduction under nitrogen restriction. The strong correlations between life stage performances that cannot be explained by pleiotropy compellingly support adaptive differentiation of yeast nitrogen source use and suggest a generic approach for detecting selection.
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| 4. |
- Lien, Sigbjorn, et al.
(författare)
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The Atlantic salmon genome provides insights into rediploidization
- 2016
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 533:7602, s. 200-205
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Tidskriftsartikel (refereegranskat)abstract
- The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.
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| 5. |
- 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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| 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. - : 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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| 7. |
- 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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| 8. |
- Warringer, Jonas, 1973, et al.
(författare)
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Trait variation in yeast is defined by population history.
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism.
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| 9. |
- Zörgö, Enikö, 1968, et al.
(författare)
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Life History Shapes Trait Heredity by Accumulation of Loss-of-Function Alleles in Yeast.
- 2012
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 29:7, s. 1781-1789
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Tidskriftsartikel (refereegranskat)abstract
- A fundamental question in biology is whether variation in organisms primarily emerges as a function of adaptation or as a function of neutral genetic drift. Trait variation in the model organism baker's yeast follows population bottlenecks rather than environmental boundaries suggesting that it primarily results from genetic drift. Based on the yeast life history, we hypothesized that population-specific loss-of-function mutations emerging in genes recently released from selection is the predominant cause of trait variation within the species. As retention of one functional copy of a gene in diploid yeasts is typically sufficient to maintain completely unperturbed performance, we also conjectured that a crossing of natural yeasts from populations with different loss-of-function mutations would provide a further efficient test bed for this hypothesis. Charting the first species-wide map of trait inheritance in a eukaryotic organism, we found trait heredity to be strongly biased toward diploid hybrid performance exactly mimicking the performance of the best of the parents, as expected given a complete dominance of functional over nonfunctional alleles. Best parent heterosis, partial dominance, and negative nonadditivity were all rare phenomena. Nonadditive inheritance was observed primarily in crosses involving at least one very poor performing parent, most frequently of the West African population, and when molecularly dissected, loss-of-function alleles were identified as the underlying cause. These findings provide support for that population-specific loss-of-function mutations do have a strong impact on genotype-phenotype maps and underscores the role of neutral genetic drift as a driver for trait variation within species.
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