The Narrow Footprint of Ancient Balancing Selection Revealed by Heterokaryon Incompatibility Genes in Aspergillus fumigatus.

In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed to be under balancing selection resulting from negative frequency-dependent selection. Here, we assess this phenomenon in Aspergillus fumigatus, a human pathogenic fungus with a very low level of linkage disequilibrium as well as an extremely high crossover rate.

The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers.

Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown.

Allorecognition genes drive reproductive isolation in Podospora anserina.

Allorecognition, the capacity to discriminate self from conspecific non-self, is a ubiquitous organismal feature typically governed by genes evolving under balancing selection. Here, we show that in the fungus Podospora anserina, allorecognition loci controlling vegetative incompatibility (het genes), define two reproductively isolated groups through pleiotropic effects on sexual compatibility. These two groups emerge from the antagonistic interactions of the unlinked loci het-r (encoding a NOD-like receptor) and het-v (encoding a methyltransferase and an MLKL/HeLo domain protein).

Flower Bulb Waste Material is a Natural Niche for the Sexual Cycle in .

With population genetic evidence of recombination ongoing in the natural population and a sexual cycle demonstrated in the laboratory the question remained what the natural niche for sex is. Composting plant-waste material is a known substrate of to thrive and withstand temperatures even up to 70°C. Previous studies have shown indirect evidence for sexual reproduction in these heaps but never directly demonstrated the sexual structures due to technical limitations.

Azole-Resistance Development; How the Lifecycle Defines the Potential for Adaptation.

In order to successfully infect or colonize human hosts or survive changing environments, needs to adapt through genetic changes or phenotypic plasticity. The genomic changes are based on the capacity of the fungus to produce genetic variation, followed by selection of the genotypes that are most fit to the new environment. Much scientific work has focused on the metabolic plasticity, biofilm formation or the particular genetic changes themselves leading to adaptation, such as antifungal resistance in the host.

Cytoplasmic Mixing, Not Nuclear Coexistence, Can Explain Somatic Incompatibility in Basidiomycetes.

Nonself recognition leading to somatic incompatibility (SI) is commonly used by mycologists to distinguish fungal individuals. Despite this, the process remains poorly understood in basidiomycetes as all current models of SI are based on genetic and molecular research in ascomycete fungi. Ascomycete fungi are mainly found in a monokaryotic stage, with a single type of haploid nuclei, and only briefly during mating do two genomes coexist in heterokaryotic cells.

Selective Flamingo Medium for the Isolation of .

For various studies in the clinic as well as the environment, it is essential to be able to selectively isolate from samples containing bacteria as well as various other fungi (mainly Mucorales). Six agar media were compared for effectiveness in selectively isolating from agricultural plant waste, woodchip waste, green waste, soil, grass and air samples collected in The Netherlands at a 48 °C incubation. The Flamingo Medium incubated at 48 °C, provided the most effective condition for the isolation of from environmental samples, since it effectively inhibited the growth of competing fungi (mainly Mucorales) present in the environmental samples.

Somatic deficiency causes reproductive parasitism in a fungus.

Some multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies.

Parasexual recombination enables to persist in cystic fibrosis.

is a saprobic fungus that causes a range of pulmonary diseases, some of which are characterised by fungal persistence such as is observed in cystic fibrosis (CF) patients. Creation of genetic variation is critical for to adapt to the lung environment, but biofilm formation, especially in CF patients, may preclude mutational supply in due to its confinement to the hyphal morphotype. We tested our hypothesis that genetic variation is created through parasexual recombination in chronic biofilms by phenotypic and genetic analysis of isolates cultured from different origins.

The taxonomy of the model filamentous fungus .

The filamentous fungus has been used as a model organism for more than 100 years and has proved to be an invaluable resource in numerous areas of research. Throughout this period, has been embroiled in a number of taxonomic controversies regarding the proper name under which it should be called. The most recent taxonomic treatment proposed to change the name of this important species to .

The Medical Triazole Voriconazole Can Select for Tandem Repeat Variations in Azole-Resistant Harboring TR/L98H Via Asexual Reproduction.

Azole-resistant isolates recovered at high frequency from patients, harbor mutations that are associated with variation of promoter length in the gene. Following the discovery of the TR/L98H genotype, new variations in tandem repeat (TR) length and number of repeats were identified, as well as additional single nucleotide polymorphisms (SNPs) in the gene, indicating that the diversity of resistance mutations in is likely to continue to increase. Investigating the development routes of TR variants is critical to be able to design preventive interventions.

Dynamics of Aspergillus fumigatus in Azole Fungicide-Containing Plant Waste in the Netherlands (2016-2017).

The treatment of patients suffering from diseases is hampered due to infections with that are already resistant to medical azoles. Previous work has suggested that likely gains resistance through environmental azole exposure in so-called hot spots. Here, we investigated resistance dynamics over time at three sites at which farmers used azole fungicides for crop protection.

Combinations of genes create multiple meiotic drivers in .

Meiotic drive is the preferential transmission of a particular allele during sexual reproduction. The phenomenon is observed as spore killing in multiple fungi. In natural populations of , seven spore killer types (s) have been identified through classical genetic analyses.

Environmental Hotspots for Azole Resistance Selection of Aspergillus fumigatus, the Netherlands.

Azole resistance is a major concern for treatment of infections with Aspergillus fumigatus. Environmental resistance selection is a main route for Aspergillus spp. to acquire azole resistance.

Mutation-rate plasticity and the germline of unicellular organisms.

The mutation rate is a fundamental factor in evolutionary genetics. Recently, mutation rates were found to be strongly reduced at high density in a wide range of unicellular organisms, prokaryotic and eukaryotic. Independently, cell division was found to become more asymmetrical at increasing density in diverse organisms; some 'mother' cells continue dividing, while their 'offspring' cells do not divide further.

Relevance of heterokaryosis for adaptation and azole-resistance development in Aspergillus fumigatus.

Aspergillus fumigatus causes a range of diseases in humans, some of which are characterized by fungal persistence. Aspergillus fumigatus, being a generalist saprotroph, may initially establish lung colonization 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.

The obligate alkalophilic soda-lake fungus Sodiomyces alkalinus has shifted to a protein diet.

Sodiomyces alkalinus is one of the very few alkalophilic fungi, adapted to grow optimally at high pH. It is widely distributed at the plant-deprived edges of extremely alkaline lakes and locally abundant. We sequenced the genome of S.

Phylogeny of Paecilomyces, the causal agent of pistachio and some other trees dieback disease in Iran.

One of the most important fungal agents of pistachio dieback disease belongs to the ascomycete genus Paecilomyces that has been identified as P. variotii. In 2012-2014, 700 plant samples from pistachio trees and 27 other plant species with dieback symptoms were collected from 10 provinces of Iran.

The alkalophilic fungus Sodiomyces alkalinus hosts beta- and gammapartitiviruses together with a new fusarivirus.

Mixed infection by three dsRNA viruses, a novel betapartitivirus, a gammapartitivirus, and a novel fusarivirus, has been identified in four isolates of the obligate alkalophilic fungus Sodiomyces alkalinus. The first, Sodiomyces alkalinus partitivirus 1 (SaPV1), is placed within the genus Betapartitivirus and is related to Ustilaginoidea virens partitivirus 2. The taxonomic position of the second virus is less clear as it shares high (85%) amino acid sequence identity but significantly low (77%) nucleotide sequence identity of the capsid protein with Colletotrichum truncatum partitivirus 1.

Evolution of cross-resistance to medical triazoles in through selection pressure of environmental fungicides.

Resistance to medical triazoles in is an emerging problem for patients at risk of aspergillus diseases. There are currently two presumed routes for medical triazole-resistance selection: (i) through selection pressure of medical triazoles when treating patients and (ii) through selection pressure from non-medical sterol-biosynthesis-inhibiting (SI) triazole fungicides which are used in the environment. Previous studies have suggested that SI fungicides can induce cross-resistance to medical triazoles.

A Novel Environmental Azole Resistance Mutation in and a Possible Role of Sexual Reproduction in Its Emergence.

This study investigated the dynamics of azole-resistant phenotypes in two compost heaps with contrasting azole exposures: azole free and azole exposed. After heat shock, to which sexual but not asexual spores are highly resistant, the azole-free compost yielded 98% (49/50) wild-type and 2% (1/50) azole-resistant isolates, whereas the azole-containing compost yielded 9% (4/45) wild-type and 91% (41/45) resistant isolates. From the latter compost, 80% (36/45) of the isolates contained the TR/Y121F/T289A genotype, 2% (1/45) harbored the TR/Y121F/M172I/T289A/G448S genotype, and 9% (4/45) had a novel pan-triazole-resistant mutation (TR/Y121F/M172I/T289A/G448S) with a triple 46-bp promoter repeat.

In-host adaptation and acquired triazole resistance in Aspergillus fumigatus: a dilemma for clinical management.

Aspergillus fumigatus causes a range of diseases in human beings, some of which are characterised by fungal persistence. A fumigatus can persist by adapting to the human lung environment through physiological and genomic changes. The physiological changes are based on the large biochemical versatility of the fungus, and the genomic changes are based on the capacity of the fungus to generate genetic diversity by spontaneous mutations or recombination and subsequent selection of the genotypes that are most adapted to the new environment.

Experimental evolution reveals that high relatedness protects multicellular cooperation from cheaters.

In multicellular organisms, there is a potential risk that cheating mutants gain access to the germline. Development from a single-celled zygote resets relatedness among cells to its maximum value each generation, which should accomplish segregation of cheating mutants from non-cheaters and thereby protect multicellular cooperation. Here we provide the crucial direct comparison between high- and low-relatedness conditions to test this hypothesis.

The diversity of microfungi in peatlands originated from the White Sea.

The diversity of culturable filamentous microfungi in peat and sediments of four peatlands at the coastal zone of Kandalaksha Bay of the White Sea (Murmansk region, Russia) was studied by culture methods on standard and selective media. Annually 100 samples were collected from the bogs 2007-2010. Based on morphological, molecular markers and cultural features, 211 taxa were identified.

Asexual sporulation facilitates adaptation: The emergence of azole resistance in Aspergillus fumigatus.

Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole resistance mutations in A. fumigatus facilitating subsequent spread through natural selection.