| 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. |
- D'Angiolo, M., et al.
(författare)
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A yeast living ancestor reveals the origin of genomic introgressions
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- A yeast clonal descendant of an ancient hybridization event is identified and sheds light on the early evolution of the Saccharomyces cerevisiae Alpechin lineage and its abundant Saccharomyces paradoxus introgressions. Genome introgressions drive evolution across the animal(1), plant(2) and fungal(3) kingdoms. Introgressions initiate from archaic admixtures followed by repeated backcrossing to one parental species. However, how introgressions arise in reproductively isolated species, such as yeast(4), has remained unclear. Here we identify a clonal descendant of the ancestral yeast hybrid that founded the extant Saccharomyces cerevisiae Alpechin lineage(5), which carries abundant Saccharomyces paradoxus introgressions. We show that this clonal descendant, hereafter defined as a 'living ancestor', retained the ancestral genome structure of the first-generation hybrid with contiguous S. cerevisiae and S. paradoxus subgenomes. The ancestral first-generation hybrid underwent catastrophic genomic instability through more than a hundred mitotic recombination events, mainly manifesting as homozygous genome blocks generated by loss of heterozygosity. These homozygous sequence blocks rescue hybrid fertility by restoring meiotic recombination and are the direct origins of the introgressions present in the Alpechin lineage. We suggest a plausible route for introgression evolution through the reconstruction of extinct stages and propose that genome instability allows hybrids to overcome reproductive isolation and enables introgressions to emerge.
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| 3. |
- 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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| 4. |
- Fredén Jansson, Karl-Johan, 1988, et al.
(författare)
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Bone Conduction Stimulated VEMP Using the B250 Transducer
- 2021
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Ingår i: Medical Devices: Evidence and Research. - 1179-1470. ; 14, s. 225-237
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Bone conduction (BC) stimulation is rarely used for clinical testing of vestibular evoked myogenic potentials (VEMPs) due to the limitations of conventional stimulation alternatives. The aim of this study is to compare VEMP using the new B250 transducer with the Minishaker and air conduction (AC) stimulation. Methods: Thirty normal subjects between 20 and 37 years old and equal gender distribution were recruited, 15 for ocular VEMP and 15 for cervical VEMP. Four stimulation conditions were compared: B250 on the mastoid (FM); Minishaker and B250 on the forehead (FZ); and AC stimulation using an insert earphone. Results: It was found that B250 at FM required a statistically significant lower hearing level than with AC stimulation, in average 41 dB and 35 dB lower for ocular VEMP and cervical VEMP, respectively, but gave longer n10 (1.1 ms) and n23 (1.6 ms). No statistical difference was found between B250 at FM and Minishaker at FZ. Conclusion: VEMP stimulated with B250 at FM gave similar response as the Minishaker at FZ and for a much lower hearing level than AC stimulation using insert earphones.
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| 5. |
- Fredén Jansson, Karl-Johan, 1988, et al.
(författare)
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Electroacoustic evaluation of the bone conduction transducer B250 for vestibular and hearing diagnostics in comparison with Radioear B71 and B81
- 2024
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Ingår i: International Journal of Audiology. - 1499-2027 .- 1708-8186. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective is to evaluate the electroacoustic performance of the B250 transducer and to compare it with the two most widely used audiometric transducers B71 and B81. Design: The electroacoustic performance was evaluated in terms of sensitivity level, distortion, maximum hearing level and electrical impedance. Study sample: Six B250 prototype transducers were evaluated and compared with published data of B71 and B81 together with complementary measurements of maximum hearing level at 125 Hz and phase of electrical impedance. Differences in reference equivalent threshold vibratory force levels were estimated by comparing hearing threshold measurements of 60 healthy ears using B81 and B250. Results: B250 has approximately 27 dB higher sensitivity levels than both B71 and B81 at 250 Hz and can generate higher maximum hearing level at low frequencies: 11.8 to 35.8 dB (125–1000 Hz) higher than B71, and 1.4 to 18.6 dB (125–750 Hz) higher than B81. The maximum average difference in reference threshold force levels was 13.5 ± 8.7 dB higher for B250 at 250 Hz compared to B81. Conclusions: B250 can produce higher output force with less distortion than B71 and B81, especially at 125 and 250 Hz, which could possibly improve low frequency investigations of the audio-vestibular system.
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| 6. |
- Håkansson, Bo, 1953, et al.
(författare)
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The bone conduction implant - a review and 1-year follow-up
- 2019
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Ingår i: International Journal of Audiology. - : Informa UK Limited. - 1499-2027 .- 1708-8186. ; 58:12, s. 945-955
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this study is to evaluate its safety and effectiveness of the bone conduction implant (BCI) having an implanted transducer and to review similar bone conduction devices. Design: This is a consecutive prospective case series study where the patients were evaluated after 1, 3, 6 and 12 months. Outcome measures were focussed on intraoperative and postoperative safety, the effectiveness of the device in terms of audiological performance and patient's experience. Study sample: Sixteen patients with average age of 40.2 (range 18-74) years have been included. Thirteen patients were operated in Gothenburg and three in Stockholm. Results: It was found that the procedure for installing the BCI is safe and the transmission condition was stable over the follow-up time. No serious adverse events or severe adverse device effects occurred. The hearing sensitivity, speech in noise and the self-assessment as compared with the unaided condition improved significantly with the BCI. These patients also performed similar or better than with a conventional bone conduction reference device on a softband. Conclusions: In summary, it was found that the BCI can provide a safe and effective hearing rehabilitation alternative for patients with mild-to-moderate conductive or mixed hearing impairments.
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| 7. |
- Johansson, Nina, 1983, et al.
(författare)
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Comparative sequence analysis and mutagenesis of Ethylene Forming Enzyme (EFE) 2-oxoglutarate/Fe(II)-dependent dioxygenase homologs
- 2014
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Ingår i: BMC Biochemistry. - : Springer Science and Business Media LLC. - 1471-2091. ; 15:1, s. Art. no. 22-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ethylene is one of the most used chemical monomers derived from non-renewable sources and we are investigating the possibility of producing it in yeast via the ethylene forming enzyme (EFE) from Pseudomonas syringae. To enable engineering strategies to improve the enzyme, it is necessary to identify the regions and amino acid residues involved in ethylene formation.Results: We identified the open reading frame for the EFE homolog in Penicillium digitatum and also showed its capability of mediating ethylene production in yeast. The sequence of the EFE homologs from P. digitatum and P. syringae was compared to that of the non-functional EFE-homolog from Penicillium chrysogenum and ten amino acids were found to correlate with ethylene production. Several of these amino acid residues were found to be important for ethylene production via point mutations in P. syringae EFE. The EFE homolog from P. chrysogenum was engineered at 10 amino acid residues to mimic the P. syringae EFE, but this did not confer ethylene producing capability. Furthermore, we predicted the structure of EFE by homology to known structures of 2-oxoglutarate/Fe(II) dependent dioxygenases. Three of the amino acids correlating with ethylene production are located in the predicted 2 oxoglutarate binding domain. A protein domain specific for the EFE class was shown to be essential for activity. Based on the structure and alanine substitutions, it is likely that amino acids (H189, D191 and H268) are responsible for binding the Fe(II) ligand.Conclusion: We provide further insight into the structure and function of the ethylene forming (EFE) - subclass of 2-oxoglutarate/Fe(II) dependent dioxygenases. We conclude that residues in addition to the 10 identified positions implicated in ethylene production by sequence comparison, are important for determining ethylene formation. We also demonstrate the use of an alternative EFE gene. The data from this study will provide the basis for directed protein engineering to enhance the ethylene production capability and properties of EFE.
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| 8. |
- Johansson, Nina, 1983, et al.
(författare)
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Ethylene production in relation to nitrogen metabolism in Saccharomyces cerevisiae
- 2014
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Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 14:7, s. 1110-1118
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that ethylene production in Saccharomyces cerevisiae expressing the ethylene-forming enzyme (EFE) from Pseudomonas syringae is strongly influenced by variations in the mode of cultivation as well as the choice of nitrogen source. Here, we have studied the influence of nitrogen metabolism on the production of ethylene further. Using ammonium, glutamate, glutamate/arginine, and arginine as nitrogen sources, it was found that glutamate (with or without arginine) correlates with a high ethylene production, most likely linked to an observed increase in 2-oxoglutarate levels. Arginine as a sole nitrogen source caused a reduced ethylene production. A reduction of arginine levels, accomplished using an arginine auxotrophic ARG4-deletion strain in the presence of limiting amounts of arginine or through CAR1 overexpression, did however not correlate with an increased ethylene production. As expected, arginine was necessary for ethylene production as ethylene production in the ARG4-deletion strain ceased at the time when arginine was depleted. In conclusion, our data suggest that high levels of 2-oxoglutarate and a limited amount of arginine are required for successful ethylene production in yeast.
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| 9. |
- Johansson, Nina, 1983, et al.
(författare)
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Expression of NADH-oxidases enhances ethylene productivity in Saccharomyces cerevisiae expressing the bacterial EFE
- 2017
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Ingår i: Biotechnology and Bioprocess Engineering. - : Springer Science and Business Media LLC. - 1226-8372 .- 1976-3816. ; 22:2, s. 195-199
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Tidskriftsartikel (refereegranskat)abstract
- Ethylene is a major petrochemical for which biotechnological production methods are an attractive alternative. Here we use a system based on a bacterial ethylene forming enzyme (EFE) expressed in Saccharomyces cerevisiae. Metabolic modelling performed in a previous study identified re-oxidation of NADH as a factor limiting ethylene production in S. cerevisiae. In line with this, we here found that strains with multicopy plasmid expression of the heterologous oxidases nox and Aox1 led to significantly increased specific ethylene productivity, up 12 and 36%, respectively, compared to the control strain with empty plasmid. However the productivity and yield was only improved in the AOX expressing strain compared to that of the control strain. Both oxidase expressing strains also exhibited increased respiration rates compared to the reference strain, with specific oxygen consumption rates being roughly doubled in both strains. The AOX strain furthermore exhibited a significant increase in the EFE substrate 2-oxoglutarate formation compared to the reference strain, linking an improvement in ethylene production to both increased respiratory capacity and increased substrate availability, thereby corroborating our previous finding.
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| 10. |
- Li, Jing, et al.
(författare)
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Shared Molecular Targets Confer Resistance over Short and Long Evolutionary Timescales
- 2019
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 36:4, s. 691-708
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Tidskriftsartikel (refereegranskat)abstract
- Pre-existing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the evolutionary dynamics in drug-treated yeast populations with different levels of pre-existing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of pre-existing variation alone boosts the adaptation by 64.1% and 51.5% in hydroxyurea and rapamycin, respectively. The causative pre-existing and de novo variants were selected on shared targets: RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. Interestingly, the pre-existing and de novo TOR variants map to different functional domains and act via distinct mechanisms. The pre-existing TOR variants from two domesticated strains exhibited opposite rapamycin resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how pre-existing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving populations.
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