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Sökning: WFRF:(Hiltunen Markus)

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1.
  • Bahram, Mohammad, et al. (författare)
  • The genome and microbiome of a dikaryotic fungus (Inocybe terrigena, Inocybaceae) revealed by metagenomics
  • 2018
  • Ingår i: Environmental Microbiology Reports. - : WILEY. - 1758-2229. ; 10:2, s. 155-166
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in molecular methods have increased our understanding of various fungal symbioses. However, little is known about genomic and microbiome features of most uncultured symbiotic fungal clades. Here, we analysed the genome and microbiome of Inocybaceae (Agaricales, Basidiomycota), a largely uncultured ectomycorrhizal clade known to form symbiotic associations with a wide variety of plant species. We used metagenomic sequencing and assembly of dikaryotic fruiting-body tissues from Inocybe terrigena (Fr.) Kuyper, to classify fungal and bacterial genomic sequences, and obtained a nearly complete fungal genome containing 93% of core eukaryotic genes. Comparative genomics reveals that I. terrigena is more similar to ectomycorrhizal and brown rot fungi than to white rot fungi. The reduction in lignin degradation capacity has been independent from and significantly faster than in closely related ectomycorrhizal clades supporting that ectomycorrhizal symbiosis evolved independently in Inocybe. The microbiome of I. terrigena fruiting-bodies includes bacteria with known symbiotic functions in other fungal and non-fungal host environments, suggesting potential symbiotic functions of these bacteria in fungal tissues regardless of habitat conditions. Our study demonstrates the usefulness of direct metagenomics analysis of fruiting-body tissues for characterizing fungal genomes and microbiome.
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2.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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3.
  • Hensen, Noah, et al. (författare)
  • Genome-scale phylogeny and comparative genomics of the fungal order Sordariales
  • 2023
  • Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier. - 1055-7903 .- 1095-9513. ; 189
  • Tidskriftsartikel (refereegranskat)abstract
    • The order Sordariales is taxonomically diverse, and harbours many species with different lifestyles and large economic importance. Despite its importance, a robust genome-scale phylogeny, and associated comparative genomic analysis of the order is lacking.In this study, we examined whole-genome data from 99 Sordariales, including 52 newly sequenced genomes, and seven outgroup taxa. We inferred a comprehensive phylogeny that resolved several contentious relationships amongst families in the order, and cleared-up intrafamily relationships within the Podosporaceae. Extensive comparative genomics showed that genomes from the three largest families in the dataset (Chae-tomiaceae, Podosporaceae and Sordariaceae) differ greatly in GC content, genome size, gene number, repeat percentage, evolutionary rate, and genome content affected by repeat-induced point mutations (RIP). All genomic traits showed phylogenetic signal, and ancestral state reconstruction revealed that the variation of the properties stems primarily from within-family evolution. Together, the results provide a thorough framework for understanding genome evolution in this important group of fungi.
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4.
  • Hiltunen, Markus, et al. (författare)
  • ARBitR : an overlap-aware genome assembly scaffolder for linked reads
  • 2021
  • Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811 .- 1460-2059. ; 37:15, s. 2203-2205
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary: Linked genomic sequencing reads contain information that can be used to join sequences together into scaffolds in draft genome assemblies. Existing software for this purpose performs the scaffolding by joining sequences with a gap between them, not considering potential overlaps of contigs. We developed ARBitR to create scaffolds where overlaps are taken into account and show that it can accurately recreate regions where draft assemblies are broken.Availability and implementation: ARBitR is written and implemented in Python3 for Unix-based operative systems. All source code is available at https://github.com/markhilt/ARBitR under the GNU General Public License v3.Contact: markus.hiltunen@ebc.uu.seSupplementary information: Supplementary data are available at Bioinformatics online.
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5.
  • Hiltunen, Markus, et al. (författare)
  • Dynamics of transposon activity and genomic rearrangements in natural and cultured isolates of the fairy-ring fungus Marasmius oreades
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • In fungi, genetic variability can be generated by an array of different mechanisms, many of which are not restricted to the sexual part of the life cycle. Many fungal species have an extended vegetative phase of the life cycle, raising the question of how important this phase is for generating diversity in fungal populations. Recent findings have revealed remarkable genome stability at the nucleotide level in mushroom-forming fungi, but if this pattern extends to include other types of genotypic changes, e.g. mitotic recombination, structural rearrangements and transposon mobilization, is still an open question. Here we used a Marasmius oreades fairy ring that had grown for an estimated 12 years in nature as a dikaryon, with two different haploid nuclei per cell, to look into this question. By separating the two nuclear genotypes from four fruiting bodies through non-meiotic techniques and generating nearly finished genome assemblies of them, we unlocked full genomic access to find and analyze changes to the genotype of any size. We found that during dikaryotic growth in nature, the genome stays intact, but after separating the nuclear genotypes through protoplasts, a considerable amount of structural variation had started to accumulate. In particular, activity of an autonomous and associated non-autonomous hAT transposons was triggered, and translocations up to several hundred kilobases were found near the telomeres. Our study adds to a growing pool of evidence that long-lived fungi are able to suppress the rise or spread of genotypic changes during dikaryotic growth. Furthermore, our results reveal that genome integrity can be interrupted if the two nuclei of the dikaryon are divorced through laboratory means, leading to genomic rearrangements and sparking the activity of transposable elements.
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6.
  • Hiltunen, Markus (författare)
  • Full circle : Rise and fate of genetic variation in Marasmius oreades fairy rings
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Genetic variation is a prerequisite for evolution. The degree of variability within a species is governed by forces including mutation, recombination and selection. In the kingdom of fungi, where periodic sexual reproduction may be interleaved with extended vegetative phases, generators of variability are not restricted to act only during sexual cycles. Such generators may be in the form of mutations to the genome, affecting single base pairs up to large-scale rearrangements, movement of transposable elements, or non-meiotic shuffling of genetic variants by mitotic recombination or parasexuality. Particularly in mushroom-forming fungi, where mycelia may become large and old, the evolutionary potential of variation acquired over vegetative growth is expected to be large. In this thesis, I have studied the rise and fate of variation gained during vegetative growth in the mushroom-forming fungus Marasmius oreades: a non-model species known for growing in ‘fairy rings’. By taking advantage of state-of-the-art genome sequencing technology and developing new bioinformatics methods, the genome sequence of M. oreades was successfully reconstructed. This resource was combined with genome re-sequencing to identify different types of mutations in M. oreades fairy rings, and to investigate the transmission of such mutations into the next generation through sexual spores. The results presented in this thesis reveal that the M. oreades genome is extremely stable at all levels during vegetative growth in its natural environment. Furthermore, the few mutations that arise do not seem to be transferred to the sexual spores. A significant amount of transposon movement was however revealed in monokaryotic strains when separated from dikaryons and grown in the laboratory. The combination of these results suggests that fungi possess an unknown system to suppress the accumulation of mutations during growth in nature, and that the apparent lack of a segregated germline in fungi potentially has to be reconsidered. Thus, contrary to expectations, the vegetative life stage in long-lived mushroom-forming fungi does not contribute much genetic variation, making these organisms more similar to animals and plants than previously considered. Further studies are needed to reveal how fungi control mutation accumulation, and elucidate if transposon activity is high also in naturally derived monokaryons in the form of meiotic progeny. The findings in this thesis add to what is known about how genetic variation is introduced into natural populations, how fungi deal with mutations, and highlight the complexity of genetic systems in mushroom-forming fungi.
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7.
  • Hiltunen, Markus, et al. (författare)
  • Maintenance of High Genome Integrity over Vegetative Growth in the Fairy-Ring Mushroom Marasmius oreades
  • 2019
  • Ingår i: Current Biology. - : CELL PRESS. - 0960-9822 .- 1879-0445. ; 29:16, s. 2758-2765
  • Tidskriftsartikel (refereegranskat)abstract
    • Most mutations in coding regions of the genome are deleterious, causing selection to favor mechanisms that minimize the mutational load over time [1-5]. DNA replication during cell division is a major source of new mutations. It is therefore important to limit the number of cell divisions between generations, particularly for large and long-lived organisms [6-9]. The germline cells of animals and the slowly dividing cells in plant meristems are adaptations to control the number of mutations that accumulate over generations [9-11]. Fungi lack a separated germline while harboring species with very large and long-lived individuals that appear to maintain highly stable genomes within their mycelia [8, 12, 13]. Here, we studied genomic mutation accumulation in the fairy-ring mushroom Marasmius oreades. We generated a chromosome-level genome assembly using a combination of cutting-edge DNA sequencing technologies and resequenced 40 samples originating from six individuals of this fungus. The low number of mutations recovered in the sequencing data suggests the presence of an unknown mechanism that works to maintain extraordinary genome integrity over vegetative growth in M. oreades. The highly structured growth pattern of M. oreades allowed us to estimate the number of cell divisions leading up to each sample [14, 15], and from this data, we infer an incredibly low per mitosis mutation rate (3.8 x 10(-12) mutations per site and cell division) as one of several possible explanations for the low number of identified mutations.
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8.
  • Hiltunen, Markus, et al. (författare)
  • No inheritance of vegetative mutations into sexual spores of the fungus Marasmius oreades
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Mutations accumulate in living cells over time and replications. In modular organisms that lack a segregated germline, mutations that arise during vegetative growth are expected to be inherited by the sexual progeny. Here we tested this hypothesis in a 12-year-old genet of the fairy-ring forming fungus Marasmius oreades, by using whole-genome sequencing of fruiting bodies and isolates from their meiotically derived basidiospores. As the fruiting bodies of a fairy ring share a common ancestor, new vegetative mutations could be identified in their genomes as variants that were unique to one or a subset of fruiting bodies. Using this approach, we identified 61 different mutations, and strikingly, none of them were recovered in the single-spore isolates from the same fruiting bodies. Purifying selection on new mutations was ruled out as factor removing mutations by investigating linked variants. We discuss different models that can account for the lack of mutation inheritance, including a cryptic germline in the fungus. Our results shed light on how new genetic variation is introduced and maintained in fungal populations.
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9.
  • Hiltunen, Markus, et al. (författare)
  • The assembled and annotated genome of the fairy-ring fungus Marasmius oreades
  • 2021
  • Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Marasmius oreades is a basidiomycete fungus that grows in so called “fairy rings”, which are circular, underground mycelia common in lawns across temperate areas of the world. Fairy rings can be thought of as natural, long-term evolutionary experiments. As each ring has a common origin and expands radially outwards over many years, different sectors will independently accumulate mutations during growth. The genotype can be followed to the next generation, as mushrooms producing the sexual spores are formed seasonally at the edge of the ring. Here we present new genomic data from 95 single-spore isolates of the species, which we used to construct a genetic linkage map and an updated version of the genome assembly. The 44 Mb assembly was anchored to 11 linkage groups, producing chromosome-length scaffolds. Gene annotation revealed 13,891 genes, 55% of which contained a pfam domain. The repetitive fraction of the genome was 22%, and dominated by retrotransposons and DNA elements of the KDZ and Plavaka groups. The level of assembly contiguity we present is so far rare in mushroom-forming fungi, and we expect studies of genomics, transposons, phylogenetics, and evolution to be facilitated by the data we present here of the iconic fairy-ring mushroom.
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10.
  • Hiltunen Thorén, Markus, et al. (författare)
  • Stage-specific transposon activity in the life cycle of the fairy-ring mushroom Marasmius oreades
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 119:46
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variability can be generated by different mechanisms, and across the life cycle. Many basidiomycete fungi have an extended somatic stage, during which each cell carries two genetically distinct haploid nuclei (dikaryosis), resulting from fusion of two compatible monokaryotic individuals. Recent findings have revealed remarkable genome stability at the nucleotide level during dikaryotic growth in these organisms, but whether this pattern extends to mutations affecting large genomic regions remains unknown. Furthermore, despite high genome integrity during dikaryosis, basidiomycete populations are not devoid of genetic diversity, begging the question of when this diversity is introduced. Here, we used a Marasmius oreades fairy ring to investigate the rise of large-scale variants during mono- and dikaryosis. By separating the two nuclear genotypes from four fruiting bodies and generating complete genome assemblies, we gained access to investigate genomic changes of any size. We found that during dikaryotic growth in nature the genome stayed intact, but after separating the nucleotypes into monokaryons, a considerable amount of structural variation started to accumulate, driven to large extent by transposons. Transposon insertions were also found in monokaryotic single-meiospore isolates. Hence, we show that genome integrity in basidiomycetes can be interrupted during monokaryosis, leading to genomic rearrangements and increased activity of transposable elements. We suggest that genetic diversification is disproportionate between life cycle stages in mushroom-forming fungi, so that the short-lived monokaryotic growth stage is more prone to genetic changes than the dikaryotic stage.
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