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

2017 ◽  
Author(s):  
Abigail L. Lind ◽  
Jennifer H. Wisecaver ◽  
Catarina Lameiras ◽  
Philipp Wiemann ◽  
Jonathan M. Palmer ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Gene Cluster ◽  
Metabolic Pathways ◽  
Point Mutations ◽  
Gene Clusters ◽  
Fungal Species ◽  
Species Variation ◽  
Gene Gain ◽  
Genome Wide ◽  
Gain And Loss

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.

scholarly journals Fungal chromatin mapping identifies BasR, as the regulatory node of bacteria-induced fungal secondary metabolism

2017 ◽  
Author(s):  
Juliane Fischer ◽  
Sebastian Y. Müller ◽  
Tina Netzker ◽  
Nils Jäger ◽  
Agnieszka Gacek-Matthews ◽  
...  
Keyword(s):  
Secondary Metabolism ◽  
Gene Cluster ◽  
Molecular Mechanisms ◽  
Effective Interaction ◽  
Chromatin Modification ◽  
Gene Clusters ◽  
Fungal Species ◽  
Transcriptional Initiation ◽  
Genome Wide ◽  
Eukaryotic Microorganisms

AbstractThe eukaryotic epigenetic machinery is targeted by bacteria to reprogram the response of eukaryotes during their interaction with microorganisms. In line, we discovered that the bacterium Streptomyces rapamycinicus triggered increased chromatin acetylation and thus activation of the silent secondary metabolism ors gene cluster leading to the production of orsellinic acid in the fungus Aspergillus nidulans. Using this model we aim at understanding molecular mechanisms of communication between bacteria and eukaryotic microorganisms based on bacteria-triggered chromatin modification. By genome-wide ChIP-seq analysis of acetylated histone H3 (H3K9ac, H3K14ac) we uncovered the unique chromatin landscape in A. nidulans upon co-cultivation with S. rapamycinicus. Genome-wide acetylation of H3K9 correlated with increased gene expression, whereas H3K14 appears to function in transcriptional initiation by providing a docking side for regulatory proteins. In total, histones belonging to six secondary metabolism gene clusters showed higher acetylation during co-cultivation including the ors, aspercryptin, cichorine, sterigmatocystin, anthrone and 2,4-dihydroxy-3-methyl-6-(2-oxopropyl)benzaldehyde gene cluster with the emericellamide cluster being the only one with reduced acetylation and expression. Differentially acetylated histones were also detected in genes involved in amino acid and nitrogen metabolism, signaling, and genes encoding transcription factors. In conjunction with LC-MS/MS and MALDI-MS imaging, molecular analyses revealed the cross-pathway control and Myb-like transcription factor BasR as regulatory nodes for transduction of the bacterial signal in the fungus. The presence of basR in other fungal species allowed forecasting the inducibility of ors-like gene clusters by S. rapamycinicus in these fungi, and thus their effective interaction with activation of otherwise silent gene clusters.

scholarly journals A Rare Thioquinolobactin Siderophore Present in a Bioactive Pseudomonas sp. DTU12.1

2019 ◽  
Vol 11 (12) ◽  
pp. 3529-3533
Author(s):  
Pavelas Sazinas ◽  
Morten Lindqvist Hansen ◽  
May Iren Aune ◽  
Marie Højmark Fischer ◽  
Lars Jelsbak
Keyword(s):  
Gene Cluster ◽  
Secondary Metabolite ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Plant Pathogens ◽  
Gene Clusters ◽  
Fungal Species ◽  
Antagonistic Activity ◽  
Evolutionary Origins

Abstract Many of the soil-dwelling Pseudomonas species are known to produce secondary metabolite compounds, which can have antagonistic activity against other microorganisms, including important plant pathogens. It is thus of importance to isolate new strains of Pseudomonas and discover novel or rare gene clusters encoding bioactive products. In an effort to accomplish this, we have isolated a bioactive Pseudomonas strain DTU12.1 from leaf-covered soil in Denmark. Following genome sequencing with Illumina and Oxford Nanopore technologies, we generated a complete genome sequence with the length of 5,943,629 base pairs. The DTU12.1 strain contained a complete gene cluster for a rare thioquinolobactin siderophore, which was previously described as possessing bioactivity against oomycetes and several fungal species. We placed the DTU12.1 strain within Pseudomonas gessardii subgroup of fluorescent pseudomonads, where it formed a distinct clade with other Pseudomonas strains, most of which also contained a complete thioquinolobactin gene cluster. Only two other Pseudomonas strains were found to contain the gene cluster, though they were present in a different phylogenetic clade and were missing a transcriptional regulator of the whole cluster. We show that having the complete genome sequence and establishing phylogenetic relationships with other strains can enable us to start evaluating the distribution and evolutionary origins of secondary metabolite clusters.

scholarly journals Comparative Genomics Reveals Broad Genetic Diversity, Extensive Recombination and Nascent Ecological Adaptation in Micrococcus luteus

2021 ◽  
Author(s):  
Yisong Li ◽  
Zhong-Zhi Sun ◽  
Jin-Cheng Rong ◽  
Bin-Bin Xie
Keyword(s):  
Genetic Diversity ◽  
Comparative Genomics ◽  
Evolutionary History ◽  
Micrococcus Luteus ◽  
Genomic Diversity ◽  
Genome Wide Association ◽  
Gene Gain ◽  
Free Living ◽  
Genome Wide ◽  
Gain Loss

Abstract Background: Micrococcus luteus is a group of actinobacteria that is widely used in biotechnology and is being thought as an emerging nosocomial pathogen. With one of the smallest genomes of free-living actinobacteria, it is found in a wide range of environments, but intraspecies genetic diversity and adaptation strategies to various environments remain unclear. Here, comparative genomics, phylogenomics, and genome-wide association studies were used to investigate the genomic diversity, evolutionary history, and the potential ecological differentiation of the species.Results: High-quality genomes of 66 M. luteus strains were downloaded from the NCBI GenBank database and core and pan-genome analysis revealed a considerable intraspecies heterogeneity. Phylogenomic analysis, gene content comparison, and average nucleotide identity calculation consistently indicated that the species has diverged into three well-differentiated clades. Population structure analysis further suggested the existence of an unknown ancestor or the fourth, yet unsampled, clade. Reconstruction of gene gain/loss events along the evolutionary history revealed both early events that contributed to the inter-clade divergence and recent events leading to the intra-clade diversity. We also found convincing evidence that recombination has played a key role of the evolutionary process of the species, with upto two-thirds of the core genes have been affected by recombination. Furthermore, distribution of mammal-associated strains (including pathogens) on the phylogenetic tree suggested that the last common ancestor had a free-living lifestyle, and a few recently diverged lineages have developed a mammal-associated lifestyle separately. Consistently, genome-wide association analysis revealed that mammal-associated strains from different lineages shared genes functionally relevant to the host-associated lifestyle, indicating a recent ecological adaption to the new host-associated habitats.Conclusions: These results revealed high intraspecies genomic diversity of M. luteus and highlighted that gene gain/loss events and extensive recombination events played key roles in the genome evolution. Our study also indicated that, as a free-living species, some lineages have recently developed or are developing a mammal-associated lifestyle. This study provides insights into the mechanisms that drive the genome evolution and adaption to various environments of a bacterial species.

scholarly journals A 90-Kilobase Conjugative Chromosomal Element Coding for Biphenyl and Salicylate Catabolism in Pseudomonas putida KF715

2000 ◽  
Vol 182 (7) ◽  
pp. 1949-1955 ◽  
Author(s):  
Akito Nishi ◽  
Kiyomi Tominaga ◽  
Kensuke Furukawa
Keyword(s):  
Benzoic Acid ◽  
Pseudomonas Putida ◽  
Gene Cluster ◽  
Metabolic Pathways ◽  
Nutrient Medium ◽  
Gene Clusters ◽  
Deletion Mutants

ABSTRACT The biphenyl and salicylate metabolic pathways in Pseudomonas putida KF715 are chromosomally encoded. The bph gene cluster coding for the conversion of biphenyl to benzoic acid and thesal gene cluster coding for the salicylatemeta-pathway were obtained from the KF715 genomic cosmid libraries. These two gene clusters were separated by 10-kb DNA and were highly prone to deletion when KF715 was grown in nutrient medium. Two types of deletions took place at the region including only thebph genes (ca. 40 kb) or at the region including both thebph and sal genes (ca. 70 kb). A 90-kb DNA region, including both the bph and sal genes (termed the bph-sal element), was transferred by conjugation from KF715 to P. putida AC30. Such transconjugants gained the ability to grow on biphenyl and salicylate as the sole sources of carbon. The bph and salelement was located on the chromosome of the recipient. Thebph-sal element in strain AC30 was also highly prone to deletion; however, it could be mobilized to the chromosome of P. putida KT2440 and the two deletion mutants of KF715.

scholarly journals Specific point mutations in Lactobacillus casei ATCC 27139 cause a phenotype switch from Lac− to Lac+

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 751-760 ◽  
Author(s):  
Yu-Kuo Tsai ◽  
Hung-Wen Chen ◽  
Ta-Chun Lo ◽  
Thy-Hou Lin
Keyword(s):  
Gene Cluster ◽  
Point Mutation ◽  
Lactobacillus Casei ◽  
Stop Codon ◽  
Single Point ◽  
Point Mutations ◽  
Premature Stop Codon ◽  
Gene Clusters ◽  
Single Point Mutation ◽  
Phenotype Switch

Lactose metabolism is a changeable phenotype in strains of Lactobacillus casei. In this study, we found that L. casei ATCC 27139 was unable to utilize lactose. However, when exposed to lactose as the sole carbon source, spontaneous Lac+ clones could be obtained. A gene cluster (lacTEGF–galKETRM) involved in the metabolism of lactose and galactose in L. casei ATCC 27139 (Lac−) and its Lac+ revertant (designated strain R1) was sequenced and characterized. We found that only one nucleotide, located in the lacTEGF promoter (lacTp), of the two lac–gal gene clusters was different. The protein sequence identity between the lac–gal gene cluster and those reported previously for some L. casei (Lac+) strains was high; namely, 96–100 % identity was found and no premature stop codon was identified. A single point mutation located within the lacTp promoter region was also detected for each of the 41 other independently isolated Lac+ revertants of L. casei ATCC 27139. The revertants could be divided into six classes based on the positions of the point mutations detected. Primer extension experiments conducted on transcription from lacTp revealed that the lacTp promoter of these six classes of Lac+ revertants was functional, while that of L. casei ATCC 27139 was not. Northern blotting experiments further confirmed that the lacTEGF operon of strain R1 was induced by lactose but suppressed by glucose, whereas no blotting signal was ever detected for L. casei ATCC 27139. These results suggest that a single point mutation in the lacTp promoter was able to restore the transcription of a fully functional lacTEGF operon and cause a phenotype switch from Lac− to Lac+ for L. casei ATCC 27139.

scholarly journals Beyond the Biosynthetic Gene Cluster Paradigm: Genome-Wide Coexpression Networks Connect Clustered and Unclustered Transcription Factors to Secondary Metabolic Pathways

2021 ◽  
Author(s):  
Min Jin Kwon ◽  
Charlotte Steiniger ◽  
Timothy C. Cairns ◽  
Jennifer H. Wisecaver ◽  
Abigail L. Lind ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Secondary Metabolites ◽  
Gene Cluster ◽  
Metabolic Pathways ◽  
Biosynthetic Gene Cluster ◽  
Bioactive Molecules ◽  
Biosynthetic Gene ◽  
Genome Wide ◽  
Coexpression Networks

There is an urgent need for novel bioactive molecules in both agriculture and medicine. The genomes of fungi are thought to contain vast numbers of metabolic pathways involved in the biosynthesis of secondary metabolites with diverse bioactivities.

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

PLoS Biology ◽  
2017 ◽  
Vol 15 (11) ◽  
pp. e2003583 ◽  
Author(s):  
Abigail L. Lind ◽  
Jennifer H. Wisecaver ◽  
Catarina Lameiras ◽  
Philipp Wiemann ◽  
Jonathan M. Palmer ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Gene Clusters ◽  
Fungal Species ◽  
Metabolic Gene

scholarly journals Comparative genomics reveals broad genetic diversity, extensive recombination and nascent ecological adaptation in Micrococcus luteus

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yisong Li ◽  
Zhong-Zhi Sun ◽  
Jin-Cheng Rong ◽  
Bin-Bin Xie
Keyword(s):  
Genetic Diversity ◽  
Comparative Genomics ◽  
Evolutionary History ◽  
Micrococcus Luteus ◽  
Genomic Diversity ◽  
Genome Wide Association ◽  
Gene Gain ◽  
Free Living ◽  
Genome Wide ◽  
Gain Loss

Abstract Background Micrococcus luteus is a group of actinobacteria that is widely used in biotechnology and is being thought as an emerging nosocomial pathogen. With one of the smallest genomes of free-living actinobacteria, it is found in a wide range of environments, but intraspecies genetic diversity and adaptation strategies to various environments remain unclear. Here, comparative genomics, phylogenomics, and genome-wide association studies were used to investigate the genomic diversity, evolutionary history, and the potential ecological differentiation of the species. Results High-quality genomes of 66 M. luteus strains were downloaded from the NCBI GenBank database and core and pan-genome analysis revealed a considerable intraspecies heterogeneity. Phylogenomic analysis, gene content comparison, and average nucleotide identity calculation consistently indicated that the species has diverged into three well-differentiated clades. Population structure analysis further suggested the existence of an unknown ancestor or the fourth, yet unsampled, clade. Reconstruction of gene gain/loss events along the evolutionary history revealed both early events that contributed to the inter-clade divergence and recent events leading to the intra-clade diversity. We also found convincing evidence that recombination has played a key role in the evolutionary process of the species, with upto two-thirds of the core genes having been affected by recombination. Furthermore, distribution of mammal-associated strains (including pathogens) on the phylogenetic tree suggested that the last common ancestor had a free-living lifestyle, and a few recently diverged lineages have developed a mammal-associated lifestyle separately. Consistently, genome-wide association analysis revealed that mammal-associated strains from different lineages shared genes functionally relevant to the host-associated lifestyle, indicating a recent ecological adaption to the new host-associated habitats. Conclusions These results revealed high intraspecies genomic diversity of M. luteus and highlighted that gene gain/loss events and extensive recombination events played key roles in the genome evolution. Our study also indicated that, as a free-living species, some lineages have recently developed or are developing a mammal-associated lifestyle. This study provides insights into the mechanisms that drive the genome evolution and adaption to various environments of a bacterial species.

Sign in / Sign up

Export Citation Format

Share Document