13 Evolution of Special Metabolism in Fungi: Concepts, Mechanisms, and Pathways

Schimek, Christine

doi:10.1007/978-3-642-19974-5_13

Cited by 7 publications

(8 citation statements)

References 222 publications

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“…Filamentous fungi produce a diverse array of small molecules that function as toxins, antibiotics, and pigments [ 1 ]. Although by definition, these so-called specialized or secondary metabolites (SMs) are not strictly necessary for growth and development, they are critical to the lifestyle of filamentous fungi [ 2 ]. For example, antibiotic SMs give their fungal producers a competitive edge in environments crowded with other microbes [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

et al. 2017

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Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here, we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed 5 general types of variation in SM gene clusters: nonfunctional gene polymorphisms; gene gain and loss polymorphisms; whole cluster gain and loss polymorphisms; allelic polymorphisms, in which different alleles corresponded to distinct, nonhomologous clusters; and location polymorphisms, in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms, the detection of which requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and nonhomologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, and genomic deletion and insertion events as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.

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Section: Introductionmentioning

confidence: 99%

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

et al. 2017

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“…Filamentous fungi produce a diverse array of small molecules that function as toxins, antibiotics, and pigments [1]. Though by definition these so-called specialized or secondary metabolites (SMs) are not strictly necessary for growth and development, they are critical to the lifestyle of filamentous fungi [2]. For example, antibiotic SMs give their fungal producers a competitive edge in environments crowded with other microbes [3].…”

Section: Introductionmentioning

confidence: 99%

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Lind

Wisecaver

Lameiras

et al. 2017

Preprint

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SummaryFilamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed five general types of variation in SM gene clusters: non-functional gene polymorphisms, gene gain and loss polymorphisms, whole cluster gain and loss polymorphisms, allelic polymorphisms where different alleles corresponded to distinct, non-homologous clusters, and location polymorphisms in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid, as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms whose detection requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and non-homologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, genomic deletion and insertion events, as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.

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“…KEYWORDS Aspergillus nidulans, secondary metabolism, intraspecific variation, horizontal gene transfer, viridicatumtoxin S econdary metabolites (SMs) are small molecules that, by definition, are not required for primary growth of the organisms that produce them but, instead, are associated with specific lifestyles of many fungi (1), including host range expansions of several fungal pathogens (2)(3)(4)(5). SMs may also provide fitness benefits to the fungi that produce them under specific nutrient environments (6) and ecological conditions (7,8).…”

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Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates

Drott

Bastos

Rokas

et al. 2020

mSphere

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The filamentous fungus Aspergillus nidulans has been a primary workhorse used to understand fungal genetics. Much of this work has focused on elucidating the genetics of biosynthetic gene clusters (BGCs) and the secondary metabolites (SMs) they produce. SMs are both niche defining in fungi and of great economic importance to humans. Despite the focus on A. nidulans, very little is known about the natural diversity in secondary metabolism within this species. We determined the BGC content and looked for evolutionary patterns in BGCs from whole-genome sequences of two clinical isolates and the A4 reference genome of A. nidulans. Differences in BGC content were used to explain SM profiles determined using liquid chromatography–high-resolution mass spectrometry. We found that in addition to genetic variation of BGCs contained by all isolates, nine BGCs varied by presence/absence. We discovered the viridicatumtoxin BGC in A. nidulans and suggest that this BGC has undergone a horizontal gene transfer from the Aspergillus section Nigri lineage into Penicillium sometime after the sections Nigri and Nidulantes diverged. We identified the production of viridicatumtoxin and several other compounds previously not known to be produced by A. nidulans. One isolate showed a lack of sterigmatocystin production even though it contained an apparently intact sterigmatocystin BGC, raising questions about other genes and processes known to regulate this BGC. Altogether, our work uncovers a large degree of intraspecies diversity in BGC and SM production in this genetic model species and offers new avenues to understand the evolution and regulation of secondary metabolism. IMPORTANCE Much of what we know about the genetics underlying secondary metabolite (SM) production and the function of SMs in the model fungus Aspergillus nidulans comes from a single reference genome. A growing body of research indicates the importance of biosynthetic gene cluster (BGC) and SM diversity within a species. However, there is no information about the natural diversity of secondary metabolism in A. nidulans. We discovered six novel clusters that contribute to the considerable variation in both BGC content and SM production within A. nidulans. We characterize a diverse set of mutations and emphasize how findings of single nucleotide polymorphisms (SNPs), deletions, and differences in evolutionary history encompass much of the variation observed in nonmodel systems. Our results emphasize that A. nidulans may also be a strong model to use within-species diversity to elucidate regulatory cross talk, fungal ecology, and drug discovery systems.

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13 Evolution of Special Metabolism in Fungi: Concepts, Mechanisms, and Pathways

Cited by 7 publications

References 222 publications

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Drivers of genetic diversity in secondary metabolic gene clusters within a fungal species

Diversity of Secondary Metabolism in Aspergillus nidulans Clinical Isolates

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