Biology subjects

Persson, K.

Publications and source records attributed to Persson, K..

17 recordsLinked to original sources

bioRxiv2026

Nationwide citizen science reveals core and rare osmotolerant yeast communities in Swedish honey

Honey represents an extreme microbial habitat, comprising >80% sugar, low pH, oxidative stress, and antimicrobial compounds. Despite these conditions, specialized yeast species persist in nectar and honey microbial communities, where their metabolic activity may contribute to honey maturation and chemistry. To characterize the diversity and functional traits of honey-associated yeasts, we conducted a nationwide citizen science survey with the help of Swedish beekeepers, yielding ~2,400 isolates from 119 honey samples across 103 locations. Sequencing of ITS and LSU barcode regions of cultured isolates identified 85 species across 26 genera, dominated by Entelexis, Starmerella, Zygosaccharomyces, Rhodotorula, Aureobasidium, and Metschnikowia. While a small number of core taxa were consistently detected across geographic and environmental gradients, most species were rare and locally restricted, indicating a highly uneven community structure. Phenotypic assays of representative strains, typically one per isolated species, revealed broad osmotolerance, with several Entelexis, Starmerella and Zygosaccharomyces strains capable of growth at up to 80% glucose. Sugar utilization experiments showed widespread fructophilic metabolism, particularly under high-sugar conditions, and this trait was enriched among the most frequently recovered taxa. Selected isolates also fermented diluted honey, altering both its volatile profile and chemical composition. Together, these results demonstrate that honey hosts a taxonomically diverse but functionally specialized yeast community shaped by strong osmotic selection. This study establishes the largest culture-based collection of honey-associated yeasts to date, underscores the value of citizen science for large-scale microbial ecology, and identifies honey as an important reservoir of osmotolerant and fructophilic yeasts with ecological and biotechnological relevance.

microbiology↗

bioRxiv2025

Impact of fluctuating environments on the fitness and robustness of evolving laboratory and industrial Saccharomyces cerevisiae strains

Adaptation occurs through the selection of beneficial mutations enhancing fitness in a specific environment. However, since environments vary across time and space, mutations that are positively selected in one environment may be less beneficial or detrimental in others. Here, we investigate the evolution of microbial robustness (i.e. a consistent fitness across many diverse environments) through the adaptive evolution of two genetically distinct Saccharomyces cerevisiae populations in fluctuating conditions, followed by fitness assays and whole-genome sequencing. Our results indicate that the haploid laboratory strain S288C achieved higher average fitness than its parental strain, particularly when evolved in fluctuating environments compared to constant environments, but did not show increased robustness. In contrast, populations of the industrial diploid strain Ethanol Red failed to achieve significant fitness improvement under both fluctuating and constant evolution regimes but became more robust. Populations that adapted to fluctuating conditions acquired mutations in genes involved with cell morphology and protein degradation. Overall, our results emphasise the importance of parental traits in shaping fitness and robustness during adaptive laboratory evolution.

evolutionary biology↗

bioRxiv2025

Divergent ecological selection causes partial reproductive isolation and vast genomic instability in yeast

Populations evolving independently in divergent environments accumulate genetic differences and potentially evolve reproductive isolation as a by-product of divergence. The speed and mechanisms underlying this process are difficult to investigate because we rarely get the opportunity to witness them in natural settings, and histories of selection and gene flow between populations are often unknown. Here, we experimentally evolved yeast for 1000 generations of evolution in both divergent and parallel environments. At regular time points during experimental evolution, we made crosses between parallel- and divergent-evolving populations to measure postzygotic reproductive isolation (gamete viability). We used whole genome population sequencing to determine the mutational load, the number and types of structural variation, and other genomic features of the parent, F1, and F2 intraspecific hybrids. We found evidence for large scale phenotypic and genome-wide differentiation in response to divergent laboratory selection. Divergent-selected populations produced hybrids with reduced gamete viability - a classic signature of postzygotic reproductive isolation in the form of hybrid breakdown. Parallel-selected populations on the other hand remained more reproductively compatible (with exceptions). We found that F2 hybrid genomes contained vast genomic instability, i.e., new structural variants (especially insertions, deletions, and interchromosomal translocations) that were not observed in parent and F1 genomes, which is likely a result of chromosome missegregation and recombination errors in hybrid meiosis. Our results provide phenotypic and genomic evidence that partial reproductive isolation evolved due to adaptation to divergent environments, consistent with predictions of ecological speciation theory.

evolutionary biology↗

bioRxiv2023

Regulation of lactose and galactose growth: Insights from a unique metabolic gene cluster in Candida intermedia

Lactose assimilation is a relatively rare trait in yeasts, and Kluyveromyces yeast species have long served as model organisms for studying lactose metabolism. Meanwhile, the metabolic strategies of most other lactose-assimilating yeasts remain unknown. In this work, we have elucidated the genetic determinants of the superior lactose-growing yeast Candida intermedia. Through genomic and transcriptomic analyses and deletion mutant phenotyping, we identified three interdependent gene clusters responsible for the metabolism of lactose and its hydrolysis product galactose: the conserved LAC cluster (LAC12, LAC4) for lactose uptake and hydrolysis, the conserved GAL cluster (GAL1, GAL7, GAL10) for galactose catabolism, and a unique "GALLAC" cluster. This novel GALLAC cluster, which has evolved through gene duplication and divergence, proved indispensable for C. intermedias growth on lactose and galactose. The cluster contains the transcriptional activator gene LAC9, second copies of GAL1 and GAL10 and the XYL1 gene encoding an aldose reductase involved in carbon overflow metabolism. Notably, the regulatory network in C. intermedia, governed by Lac9 and Gal1 from the GALLAC cluster, differs significantly from the (ga)lactose regulons in Saccharomyces cerevisiae, Kluyveromyces lactis and Candida albicans. Moreover, although lactose and galactose metabolism are closely linked in C. intermedia, our results also point to important regulatory differences. This study paves the way to a better understanding of lactose and galactose metabolism in C. intermedia and provides new evolutionary insights into yeast metabolic pathways and regulatory networks. In extension, the results will facilitate future development and use of C. intermedia as a cell-factory for conversion of lactose-rich whey into value-added products.

microbiology↗

bioRxiv2023

Mapping Cerebellar Anatomical Heterogeneity in Mental and Neurological Illnesses

The cerebellum has been linked to motor coordination, cognitive and affective processing, in addition to a wide range of clinical illnesses. To enable robust quantification of individual cerebellar anatomy relative to population norms, we mapped the normative development and aging of the cerebellum across the lifespan using brain scans of > 54k participants. We estimated normative models at voxel-wise spatial precision, enabling integration with cerebellar atlases. Applying the normative models in independent samples revealed substantial heterogeneity within five clinical illnesses: autism spectrum disorder, mild cognitive impairment, Alzheimers disease, bipolar disorder, and schizophrenia. Notably, individuals with autism spectrum disorder and mild cognitive impairment exhibited increased numbers of both positive and negative extreme deviations in cerebellar anatomy, while schizophrenia and Alzheimers disease predominantly showed negative deviations. Finally, extreme deviations were associated with cognitive scores. Our results provide a voxel-wise mapping of cerebellar anatomy across the human lifespan and clinical illnesses, demonstrating cerebellums nuanced role in shaping human neurodiversity across the lifespan and in different clinical illnesses.

neuroscience↗

bioRxiv2022

Adaptation of the yeast gene knockout collection is near-perfectly predicted by fitness and diminishing return epistasis

Adaptive evolution of clonally dividing cells and microbes is the ultimate cause of cancer and infectious diseases. The possibility of constraining the adaptation of cell populations, by inhibiting proteins that enhance their evolvability has therefore attracted substantial interest. However, our current understanding of how individual genes influence the speed of adaptation is limited, partly because accurately tracking adaptation for many experimental cell populations in parallel is challenging. Here we use a high throughput artificial laboratory evolution (ALE) platform to track the adaptation of >18.000 cell populations corresponding to single gene deletion strains in the haploid yeast deletion collection. We report that the fitness of gene knockout near-perfectly (R2=0.91) predicts their adaptation dynamics under arsenic exposure, leaving virtually no role for dedicated evolvability functions in the corresponding proteins. We tracked the adaptation of another >23.000 yeast gene knockout populations to a diverse range of selection pressures and generalised the almost perfect (R2=0.72 to 0.98) capacity of initial fitness to predict the rate of adaptation. Finally, we reconstruct mutations in the genes FPS1, ASK10, and ARR3, which together account for almost all arsenic adaptation in wildtype cells, in gene deletions covering a broad fitness range. We show that the predictability of arsenic adaptation can be understood almost entirely as a global epistasis phenomenon where excluding arsenic from cells, through these mutations, is more beneficial in cells with low arsenic fitness regardless of what causes the arsenic defects. The lack of genes with a meaningful effect on the adaptation dynamics of clonally reproducing cell populations diminishes the prospects of developing adjuvant drugs aiming to slow antimicrobial and chemotherapy resistance.

evolutionary biology↗

bioRxiv2021

Protein-lipid interaction at low pH induces oligomerisation of the MakA cytotoxin from Vibrio cholerae

Many pathogenic bacteria produce protein toxins that target and perturb host cell membranes. The secreted -pore-forming toxins (-PFTs) cause membrane damage via pore formation. This study demonstrates a remarkable, hitherto unknown mechanism by an -PFT protein from Vibrio cholerae. As part of the MakA/B/E tripartite toxin, MakA is involved in membrane pore formation similar to other -PFTs. In contrast, MakA protein alone induces tube-like structures in the acidic lysosomal host cell compartment. In vitro studies unravel the dynamics of tubular growth, which occur in a pH-, lipid- and concentration-dependent manner. A 3.7-[A] cryo-electron microscopy structure of MakA filaments reveals a unique protein-lipid superstructure. In its active -PFT conformation, MakA embeds its transmembrane helices into a thin annular lipid bilayer and spirals around a central cavity. Our study provides molecular insights into a novel tubulation mechanism of an -PFT protein, revealing a new mode of action by a secreted bacterial toxin.

cell biology↗

bioRxiv2021

A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion

The protein MakA was discovered as a motility-associated secreted toxin from Vibrio cholerae, Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD and MakE. The MakA, MakB and MakE proteins were readily detected in culture supernatants of wild type V. cholerae whereas secretion was very much reduced from a flagellum deficient mutant. Crystal structures of MakA, MakB and MakE revealed structural relationship to a superfamily of bacterial pore-forming proteins. Cloning and expression of MakA/B/E in Escherichia coli resulted in toxicity of the bacteria towards Caenorhabditis elegans used as a predatory organism model. None of these Mak proteins alone or in pairwise combinations were cytolytic but an equimolar mixture of MakA, MakB and MakE acted as a tripartite cytolytic toxin in vitro causing lysis of erythrocytes and cytotoxicity on cultured human colon carcinoma cells. Formation of oligomeric complexes on liposomes was observed by electron microscopy. Oligomer interaction with membranes was initiated by MakA membrane binding followed by MakB and MakE joining in formation of a pore structure. A predicted membrane insertion domain of MakA was shown by site-directed mutagenesis to be essential for toxicity towards C. elegans. Bioinformatic analyses revealed that the makCDBAE gene cluster is present as a novel genomic island in the vast majority of sequenced genomes of V. cholerae and the fish pathogen V. anguillarum. We suggest that the hitherto unrecognized cytolytic MakA/B/E toxin can contribute to Vibrionaceae fitness and virulence potential in different host environments and organisms. Significance StatementVibrio cholerae, responsible for outbreaks and pandemics of cholera disease, is a highly motile organism by virtue of a single flagellum. We describe that the flagellum facilitates the secretion of three V. cholerae proteins encoded by a hitherto unrecognized novel genomic island. The proteins MakA/B/E can form a tripartite cytolytic toxin that lyses erythrocytes and is cytotoxic to cultured human cells. A structural basis for the Mak protein cytolytic activity was obtained by X-ray crystallography. Flagellum-facilitated secretion, remarkably ensuring spatially co-ordinated delivery of Mak proteins, revealed a new role for the V. cholerae flagellum considered of particular significance for the bacterial environmental persistence. Our findings will pave the way for the development of new diagnostics and therapeutic strategies against pathogenic Vibrionaceae.

biochemistry↗

bioRxiv2021

Panacea: a hyperpromiscuous antitoxin protein domain for the neutralisation of diverse toxin domains

Toxin-Antitoxin (TA) gene pairs are ubiquitous in microbial chromosomal genomes and plasmids, as well as bacteriophages. They act as regulatory switches, with the toxin limiting the growth of bacteria and archaea by compromising diverse essential cellular targets, and the antitoxin counteracting the toxic effect. To uncover previously uncharted TA diversity across microbes and bacteriophages, we analysed the conservation of genomic neighbourhoods using our computational tool FlaGs (for Flanking Genes), which allows high-throughput detection of TA-like operons. Focussing on the widespread but poorly experimentally characterised antitoxin domain DUF4065, our in silico analyses indicated that DUF4065-containing proteins serve as broadly distributed antitoxin components in putative TA-like operons with dozens of different toxic domains with multiple different folds. Given the versatility of DUF4065, we have renamed the domain to Panacea (and proteins containing the domain, PanA) after the Greek goddess of universal remedy. We have experimentally validated nine PanA-neutralised TA pairs. While the majority of validated PanA-neutralised toxins act as translation inhibitors or membrane disruptors, a putative nucleotide cyclase toxin from a Burkholderia prophage compromises replication and translation, as well as inducing RelA-dependent accumulation of the nucleotide alarmone (p)ppGpp. We find that Panacea-containing antitoxins form a complex with their diverse cognate toxins, characteristic of the direct neutralisation mechanisms employed by Type II TA systems. Finally, through directed evolution we have selected PanA variants that can neutralise non-cognate TA toxins, thus experimentally demonstrating the evolutionary plasticity of this hyperpromiscuous antitoxin domain. SignificanceToxin-antitoxin systems are enigmatic and diverse elements of bacterial and bacteriophage genomes. We have uncovered remarkable versatility of an antitoxin protein domain, that has evolved to neutralise dozens of different toxin domains. We find that antitoxins carrying this domain - Panacea - form complexes with their cognate toxins, indicating a direct neutralisation mechanism, and that Panacea can be evolved to neutralise a non-cognate and non-homologous toxin with just two amino acid substitutions. This raises the possibility that this domain could be an adaptable universal, or semi-universal protein neutraliser with significant biotechnological and medical potential.

microbiology↗

bioRxiv2021

High-resolution model of Arabidopsis Photosystem II reveals the structural consequences of digitonin-extraction

In higher plants, the photosynthetic process is performed and regulated by Photosystem II (PSII). Arabidopsis thaliana was the first higher plant with a fully sequenced genome, conferring it the status of a model organism; nonetheless, a high-resolution structure of its Photosystem II is missing. We present the first Cryo-EM high-resolution structure of Arabidopsis PSII supercomplex with average resolution of 2.79 [A], an important model for future PSII studies. The digitonin extracted PSII complexes demonstrate the importance of: the LHG2630-lipid-headgroup in the trimerization of the light-harvesting complex II; the stabilization of the PsbJ subunit and the CP43-loop E by DGD520-lipid; the choice of detergent for the integrity of membrane protein complexes. Furthermore, our data shows at the anticipated Mn4CaO5-site a single metal ion density as a reminiscent early stage of Photosystem II photoactivation.

plant biology↗

bioRxiv2020

Aborting meiosis overcomes hybrid sterility

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-of-heterozygosity 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. One sentence summaryAborting meiosis followed by a return to mitotic growth promotes evolution by genome wide-recombination in sterile yeast hybrids.

genetics↗

bioRxiv2020

Control of mitochondrial superoxide production includes programmed mtDNA deletion and restoration

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 yeasts defenses against oxidative damage.

cell biology↗

bioRxiv2020

The Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy

Autophagy plays an essential role in the defence against many microbial pathogens as a regulator of both innate and adaptive immunity. Among some pathogens, sophisticated mechanisms have evolved that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy subversion mediated by the recently discovered Vibrio cholerae cytotoxin, MakA. pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex required for LC3 lipidation at the membranous aggregate resulted in an inhibition of both canonical autophagy and autophagy-related processes including the unconventional secretion of IL-1β. These findings identify a novel mechanism of host autophagy subversion and immune modulation employed by V. cholerae during bacterial infection.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cell biology↗

bioRxiv2020

Domestication reprogrammed the budding yeast life cycle

Domestication of plants and animals is the foundation for feeding the world population. We report that domestication of the model yeast S. cerevisiae reprogrammed its life cycle entirely. We tracked growth, gamete formation and cell survival across many environments for nearly 1000 genome sequenced isolates and found a remarkable dichotomy between domesticated and wild yeasts. Wild yeasts near uniformly trigger meiosis and sporulate when encountering nutrient depletions, whereas domestication relaxed selection on sexual reproduction and favoured survival as quiescent cells. Domestication also systematically enhanced fermentative over respiratory traits while decreasing stress tolerance. We show that this yeast domestication syndrome was driven by aneuploidies and gene function losses that emerged independently in multiple domesticated lineages during the species recent evolutionary history. We found domestication to be the most dramatic event in budding yeast evolution, raising questions on how much domestication has distorted our understanding of this key model species.

evolutionary biology↗

bioRxiv2019

The Dps4 from Nostoc punctiforme ATCC 29133 is a member of His-type FOC containing Dps protein class that can be broadly found among cyanobacteria

Dps proteins (DNA-binding proteins from starved cells) have been found to detoxify H2O2. At their catalytic centers, the ferroxidase center (FOC), Dps proteins utilize Fe2+ to reduce H2O2 and therefore play an essential role in the protection against oxidative stress and maintaining iron homeostasis. Whereas most bacteria accommodate one or two Dps, there are five different Dps proteins in Nostoc punctiforme, a phototrophic and filamentous cyanobacterium. This uncommonly high number of Dps proteins implies a sophisticated machinery for maintaining complex iron homeostasis and for protection against oxidative stress. Functional analyses and structural information on cyanobacterial Dps proteins are rare, but essential for understanding the function of each of the NpDps proteins. In this study, we present the crystal structure of NpDps4 in its metal-free, iron- and zinc-bound forms. The FOC coordinates either two iron atoms or one zinc atom. Spectroscopic analyses revealed that NpDps4 could oxidize Fe2+ utilizing O2, but no evidence for its use of the oxidant H2O2 could be found. We identified Zn2+ to be an effective inhibitor of the O2-mediated Fe2+ oxidation in NpDps4. NpDps4 exhibits a FOC that is very different from canonical Dps, but structurally similar to the atypical one from DpsA of Thermosynechococcus elongatus. Sequence comparisons among Dps protein homologs to NpDps4 within the cyanobacterial phylum led us to classify a novel FOC class: the His-type FOC. The features of this special FOC have not been identified in Dps proteins from other bacterial phyla and it might be unique to cyanobacterial Dps proteins.

biochemistry↗

bioRxiv2019

Intragenic repeat expansions control yeast chronological aging

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 massive expansions of intragenic tandem repeats in the cell wall glycoproteins FLO11 and HPF1, which caused a dramatic life span shortening. Life span impairment by N-terminal HPF1 repeat expansion was partially 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 perturbed methionine, lipid, and purine metabolism, which likely 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 life style and longevity.

genomics↗

bioRxiv2017

Patterns of selection reveal shared molecular targets over short and long evolutionary timescales

Standing 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 dynamics of drug adaptation in yeast populations with different levels of standing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of standing variation alone boost the adaptation by 64.1% and 51.5% in hydroxyuea and rapamycin respectively. The causative standing and de novo variants were selected on shared targets of RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. The standing and de novo TOR variants map to different functional domains and act via distinct mechanisms. Interestingly, standing TOR variants from two domesticated strains exhibited opposite resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how standing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving diseases.

genetics↗