Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Data from: Relevance of heterokaryosis for adaptation and azole-resistance development in Aspergillus fumigatus
    Zhang, J. ; Snelders, E. ; Zwaan, B.J. ; Schoustra, S.E. ; Kuijper, Ed J. ; Arendrup, Maiken C. ; Melchers, Willem J.G. ; Verweij, Paul E. ; Debets, A.J.M. - \ 2019
    Wageningen University & Research
    heterokaryon incompatibility - azole resistance - flexible nuclear ratio - Aspergillus fumigatus
    Aspergillus fumigatus causes a range of diseases in humans, some of which are characterized by fungal persistence. A. fumigatus, being a generalist saprotroph, may initially establish lung colonisation due to its physiological versatility and subsequently adapt through genetic changes to the human lung environment and antifungal treatments. Human lung-adapted genotypes can arise by spontaneous mutation and/or recombination and subsequent selection of the fittest genotypes. Sexual and asexual spores are considered crucial contributors to the genetic diversity and adaptive potential of aspergilli by recombination and mutation supply respectively. However, in certain Aspergillus diseases, such as cystic fibrosis and chronic pulmonary aspergillosis, A. fumigatus may not sporulate but persist as a network of fungal mycelium. During azole therapy, such mycelia may develop patient-acquired resistance and become heterokaryotic by mutations in one of the nuclei. We investigated the relevance of heterokaryosis for azole-resistance development in A. fumigatus. We found evidence for heterokaryosis of A. fumigatus in patients with chronic Aspergillus diseases. Mycelium from patient-tissue biopsies segregated different homokaryons, from which heterokaryons could be reconstructed. Whereas all variant homokaryons recovered from the same patient were capable of forming a heterokaryon, those from different patients were heterokaryon-incompatible. We furthermore compared heterokaryons and heterozygous diploids constructed from environmental isolates with different levels of azole resistance. When exposed to azole, the heterokaryons revealed remarkable shifts in their nuclear ratio, and the resistance level of heterokaryons exceeded that of the corresponding heterozygous diploids.
    Experimental demonstration of the benefits of somatic fusion and the consequences for allorecognition
    Bastiaans, E. ; Debets, A.J.M. ; Aanen, D.K. - \ 2015
    multicellularity - social evolution - kin selection - ascomycete fungi - heterokaryon incompatibility
    Allorecognition, the ability to distinguish ‘self’ from ‘non-self’ based on allelic differences at allorecognition loci, is common in all domains of life. Allorecognition restricts the opportunities for social parasitism, and is therefore crucial for the evolution of cooperation. However, the maintenance of allorecognition diversity provides a paradox. If allorecognition is costly relative to cooperation, common alleles will be favored. Thus, the cost of allorecognition may reduce the genetic variation upon which allorecognition crucially relies, a prediction now known as ‘Crozier's paradox’. We establish the relative costs of allorecognition, and their consequences for the short-term evolution of recognition labels theoretically predicted by Crozier. We use fusion among colonies of the fungus Neurospora crassa, regulated by highly variable allorecognition genes, as an experimental model system. We demonstrate that fusion among colonies is mutually beneficial, relative to absence of fusion upon allorecognition. This benefit is due not only to absence of mutual antagonism, which occurs upon allorecognition, but also to an increase in colony size per se. We then experimentally demonstrate that the benefit of fusion selects against allorecognition diversity, as predicted by Crozier. We discuss what maintains allorecognition diversity.
    Experimental demonstration of the benefits of somatic fusion and the consequences for allorecognition
    Bastiaans, E. ; Debets, A.J.M. ; Aanen, D.K. - \ 2015
    Evolution 69 (2015)4. - ISSN 0014-3820 - p. 1091 - 1099.
    vegetative incompatibility - neurospora-crassa - heterokaryon incompatibility - natural-populations - filamentous fungi - recognition - evolution - selection - genetics - cooperation
    Allorecognition, the ability to distinguish “self” from “nonself” based on allelic differences at allorecognition loci, is common in all domains of life. Allorecognition restricts the opportunities for social parasitism, and is therefore crucial for the evolution of cooperation. However, the maintenance of allorecognition diversity provides a paradox. If allorecognition is costly relative to cooperation, common alleles will be favored. Thus, the cost of allorecognition may reduce the genetic variation upon which allorecognition crucially relies, a prediction now known as “Crozier's paradox.” We establish the relative costs of allorecognition, and their consequences for the short-term evolution of recognition labels theoretically predicted by Crozier. We use fusion among colonies of the fungus Neurospora crassa, regulated by highly variable allorecognition genes, as an experimental model system. We demonstrate that fusion among colonies is mutually beneficial, relative to absence of fusion upon allorecognition. This benefit is due not only to absence of mutual antagonism, which occurs upon allorecognition, but also to an increase in colony size per se. We then experimentally demonstrate that the benefit of fusion selects against allorecognition diversity, as predicted by Crozier. We discuss what maintains allorecognition diversity
    High prevalence of a fungal prion
    Debets, A.J.M. ; Dalstra, H.J.P. ; Slakhorst, S.M. ; Koopmanschap-Memelink, A.B. ; Hoekstra, R.F. ; Saupe, S.J. - \ 2012
    Proceedings of the National Academy of Sciences of the United States of America 109 (2012)26. - ISSN 0027-8424 - p. 10432 - 10437.
    podospora-anserina - vegetative incompatibility - het-s - heterokaryon incompatibility - neurospora-crassa - meiotic drive - yeast prion - mechanism - diseases - genes
    Prions are infectious proteins that cause fatal diseases in mammals. Prions have also been found in fungi, but studies on their role in nature are scarce. The proposed biological function of fungal prions is debated and varies from detrimental to benign or even beneficial. [Het-s] is a prion of the fungus Podospora anserina. The het-s locus exists as two antagonistic alleles that constitute an allorecognition system: the het-s allele encoding the protein variant capable of prion formation and the het-S allele encoding a protein variant that cannot form a prion. We document here that het-s alleles, capable of prion formation, are nearly twice as frequent as het-S alleles in a natural population of 112 individuals. Then, we report a 92% prevalence of [Het-s] prion infection among the het-s isolates and find evidence of the role of the [Het-s]/het-S allorecognition system on the incidence of infection by a deleterious senescence plasmid. We explain the het-s/het-S allele ratios by the existence of two selective forces operating at different levels. We propose that during the somatic stage, the role of [Het-s]/HET-S in allorecognition leads to frequency-dependent selection for which an equilibrated frequency would be optimal. However, in the sexual cycle, the [Het-s] prion causes meiotic drive favoring the het-s allele. Our findings indicate that [Het-s] is a selected and, therefore, widespread prion whose activity as selfish genetic element is counteracted by balancing selection for allorecognition polymorphism
    Identification of the het-r vegetative incompatibility gene of Podospora anserina as a member of the fast evolving HNWD gene family
    Chevanne, D. ; Bastiaans, E. ; Debets, A.J.M. ; Saupe, S.J. ; Clave, C. ; Paoletti, M. - \ 2009
    Current Genetics 55 (2009)1. - ISSN 0172-8083 - p. 93 - 102.
    programmed cell-death - chestnut blight fungus - non-self recognition - heterokaryon incompatibility - neurospora-crassa - filamentous fungi - virus transmission - protein - locus - domain
    In fungi, vegetative incompatibility is a conspecific non-self recognition mechanism that restricts formation of viable heterokaryons when incompatible alleles of specific het loci interact. In Podospora anserina, three non-allelic incompatibility systems have been genetically defined involving interactions between het-c and het-d, het-c and het-e, het-r and het-v. het-d and het-e are paralogues belonging to the HNWD gene family that encode proteins of the STAND class. HET-D and HET-E proteins comprise an N-terminal HET effector domain, a central GTP binding site and a C-terminal WD repeat domain constituted of tandem repeats of highly conserved WD40 repeat units that define the specificity of alleles during incompatibility. The WD40 repeat units of the members of this HNWD family are undergoing concerted evolution. By combining genetic analysis and gain of function experiments, we demonstrate that an additional member of this family, HNWD2, corresponds to the het-r non-allelic incompatibility gene. As for het-d and het-e, allele specificity at the het-r locus is determined by the WD repeat domain. Natural isolates show allelic variation for het-r
    The social evolution of somatic fusion
    Aanen, D.K. ; Debets, A.J.M. ; Visser, J.A.G.M. de; Hoekstra, R.F. - \ 2008
    Bioessays 30 (2008)11-12. - ISSN 0265-9247 - p. 1193 - 1203.
    conidial anastomosis tubes - programmed cell-death - double-stranded-rna - vegetative incompatibility - heterokaryon incompatibility - neurospora-crassa - filamentous fungi - podospora-anserina - aspergillus-nidulans - allorecognition specificity
    The widespread potential for somatic fusion among different conspecific multicellular individuals suggests that such fusion is adaptive. However, because recognition of non-kin (allorecognition) usually leads to a rejection response, successful somatic fusion is limited to close kin. This is consistent with kin-selection theory, which predicts that the potential cost of fusion and the potential for somatic parasitism decrease with increasing relatedness. Paradoxically, however, Crozier[1] found that, in the short term, positive-frequency-dependent selection eliminates the required genetic polymorphism at allorecognition loci. The Crozier paradox may be solved if allorecognition is based on extrinsically balanced polymorphisms, for example at immune loci. Alternatively, the assumption of most models that self fusion is mutually beneficial is wrong. If fusion is on average harmful, selection will promote unconditional rejection. However, we propose that fusion within individuals is beneficial, selecting for the ability to fuse, but fusion between individuals on average costly, selecting for non-self recognition (rather than non-kin recognition)
    Nonmendelian inheritance of the HET-s prion or HET-s prion domains determines the het-S spore killing system in Podospora anserina
    Dalstra, H.J.P. ; Zee, R.I. van der; Swart, K. ; Hoekstra, R.F. ; Saupe, S.J. ; Debets, A.J.M. - \ 2005
    Fungal Genetics and Biology 42 (2005)10. - ISSN 1087-1845 - p. 836 - 847.
    meiotic drive - heterokaryon incompatibility - vegetative incompatibility - in-vivo - protein - neurospora - fungi - organization - analog - genes
    Two alleles of the het-s/S locus occur naturally in the filamentous fungus Podospora anserina, het-s and het-S. The het-s encoded protein can form a prion that propagates a self-perpetuating amyloid aggregate, resulting in two phenotypes for the het-s strains. The prion-infected [Het-s] shows an antagonistic interaction to het-S whereas the prion-free [Het-s*] is neutral in interaction to het-S. The antagonism between [Het-s] and het-S is seen as heterokaryon incompatibility at the somatic level and as het-S spore killing in the sexual cycle. Two different domains of the HET-s and HET-S proteins have been identified, and a structure-function relationship has been established for interactions at the somatic level. In this study, we correlate accumulation of the HET-s and HET-S proteins (visualized using GFP) during the sexual cycle with timing of het-S spore abortion. Also, we present the structure-function relationship of the HET-s domains for interactions in the sexual cycle. We show that the constructs that ensure het-s incompatibility function in somatic mycelium are also active in het-S spore killing in the sexual cycle. In addition, paternal prion transmission and het-S spore killing has been found with the HET-s(157-289) truncated protein. The consequences of the unique transition from a coenocytic to a cellular state in the sexual phase and the timing, and localization of paternal and maternal HET-s and HET-S expression that are pertinent to prion transmission, and het-S spore killing are elaborated. These data further support our previously proposed model for het-S spore killing.
    Spore killing in the fungus Podospora anserina: a possible connection between meiotic drive and vegetative incompatibility
    Gaag, M. van der; Debets, A.J.M. ; Hoekstra, R.F. - \ 2003
    Genetica 117 (2003)1. - ISSN 0016-6707 - p. 59 - 65.
    heterokaryon incompatibility - natural-populations - neurospora - plasmids - dynamics
    Fungi in which the haploid nuclei resulting from meiosis are linearly arranged in asci provide unique opportunities to analyse abnormal segregation. Any meiotic drive system in such fungi will be observed in a cross between a driving and a sensitive strain as spore killing: the degeneration of half the ascospores in a certain proportion of the asci. In a sample of some 100 strains isolated from a single natural population we have discovered at least six different meiotic drive elements (van der Gaag et al., 2000). Here we report results of research that was aimed at elucidating a possible correlation between meiotic drive and vegetative incompatibility in eight different Spore killer strains from this population. We show that there is a strong correlation between these two phenotypes, although the precise genetic nature of the correlation is not yet clear. We discuss the implications of our results for the understanding of the population genetics of meiotic drive in Podospora
    Male and female roles in crosses of Aspergillus nidulans as revealed by vegetatively incompatible parents
    Bruggeman, I.M. ; Debets, A.J.M. ; Swart, K. ; Hoekstra, R.F. - \ 2003
    Fungal Genetics and Biology 39 (2003). - ISSN 1087-1845 - p. 136 - 141.
    heterokaryon incompatibility - neurospora-crassa - inheritance - evolution - mutants - meiosis - genome - nuclei
    To resolve the role of male and female nuclei and mitochondria in cleistothecium formation in the model organism Aspergillus nidulans, we analysed the genetic constituents of cleistothecia, from crosses between vegetatively compatible and incompatible parents. We used markers that enabled us to determine the nuclear genotype of the cleistothecial wall and the nuclear and mitochondrial genotype of the ascospores. In compatible parents, nuclear genomes and cytoplasm usually mix in the vegetative hyphae prior to the formation of the sexual stage after which any cleistothecial composition is possible. In incompatible parents, the maternal strain contributes the nuclei for the cleistothecial wall and one nucleus as well as mitochondria for the ascospore origin. The paternal strain donates one nucleus for the ascospore origin. Only in crosses between vegetatively incompatible partners, it is possible to assign a female and male role to the parental strains. Our results confirm that the vegetative heterokaryotic stage is not a prerequisite for cleistothecium formation. Using this tool, we analysed sexual sporulation mutants for male or female sterility. (C) 2003 Elsevier Science (USA). All rights reserved.
    Sexual transmission of the [Het-s] prion leads to meiotic drive in Podospora anserina
    Dalstra, H.J.P. ; Swart, K. ; Debets, A.J.M. ; Saupe, S.J. ; Hoekstra, R.F. - \ 2003
    Proceedings of the National Academy of Sciences of the United States of America 100 (2003). - ISSN 0027-8424 - p. 6616 - 6621.
    fungus podospora-anserina - heterokaryon incompatibility - spore killer - filamentous fungi - neurospora - protein - elements - products - meiosis - analog
    In the filamentous fungus Podospora anserina, two phenomena are associated with polymorphism at the het-s locus, vegetative incompatibility and ascospore abortion. Two het-s alleles occur naturally, het-s and het-S. The het-s encoded protein is a prion propagating as a self-perpetuating amyloid aggregate. When prion-infected [Het-s] hyphae fuse with [Het-S] hyphae, the resulting heterokaryotic cells necrotize. [Het-s] and [Het-S] strains are sexually compatible. When, however, a female [Het-s] crosses with [Het-S], a significant percentage of het-S spores abort, in a way similar to spore killing in Neurospora and Podospora. We report here that sexual transmission of the [Het-s] prion after nonisogamous mating in the reproductive cycle of Podospora is responsible for the killing of het-S spores. Progeny of crosses between isogenic strains with distinct wild-type or introduced, ectopic het-s/S alleles were cytologically and genetically analyzed. The effect of het-s/S overexpression, ectopic het-s/S expression, absence of het-s expression, loss of [Het-s] prion infection, and the distribution patterns of HET-s/S-GFP proteins were categorized during meiosis and ascospore formation. This study unveiled a het-S spore-killing system that is governed by dosage of and interaction between the [Het-s] prion and the HET-S protein. Due to this property of the [Het-s] prion, the het-s allele acts as a meiotic drive element favoring maintenance of the prion-forming allele in natural populations.
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