Depside and Depsidone Synthesis in Lichenized Fungi Comes into Focus through a Genome-Wide Comparison of the Olivetoric Acid and Physodic Acid Chemotypes of Pseudevernia furfuracea

Primary biosynthetic enzymes involved in the synthesis of lichen polyphenolic compounds depsides and depsidones are non-reducing polyketide synthases (NR-PKSs), and cytochrome P450s. However, for most depsides and depsidones the corresponding PKSs are unknown. Additionally, in non-lichenized fungi specific fatty acid synthases (FASs) provide starters to the PKSs. Yet, the presence of such FASs in lichenized fungi remains to be investigated. Here we implement comparative genomics and metatranscriptomics to identify the most likely PKS and FASs for olivetoric acid and physodic acid biosynthesis, the primary depside and depsidone defining the two chemotypes of the lichen Pseudevernia furfuracea. We propose that the gene cluster PF33-1_006185, found in both chemotypes, is the most likely candidate for the olivetoric acid and physodic acid biosynthesis. This is the first study to identify the gene cluster and the FAS likely responsible for olivetoric acid and physodic acid biosynthesis in a lichenized fungus. Our findings suggest that gene regulation and other epigenetic factors determine whether the mycobiont produces the depside or the depsidone, providing the first direct indication that chemotype diversity in lichens can arise through regulatory and not only through genetic diversity. Combining these results and existing literature, we propose a detailed scheme for depside/depsidone synthesis.

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Depside and depsidone synthesis in lichenized fungi comes into focus through a genome-wide comparison of the olivetoric and physodic acid chemotype of Pseudevernia furfuracea

10.1101/2021.09.07.459332 ◽

2021 ◽

Author(s):

Garima Singh ◽

Daniele Armaleo ◽

Francesco Dal Grande ◽

Imke Schmitt

Keyword(s):

Gene Cluster ◽

Fatty Acyl ◽

Lichenized Fungi ◽

Acid Biosynthesis ◽

Pseudevernia Furfuracea ◽

Genome Wide ◽

A Genome ◽

Direct Indication ◽

Chemotype Diversity ◽

Lichenized Fungus

ABSTRACTPrimary biosynthetic enzymes involved in the synthesis of lichen polyphenolic compounds depsides and depsidones are Non-Reducing Polyketide Synthases (NR-PKSs), and cytochrome P450s (CytP450). However, for most depsides and depsidones the corresponding PKSs are unknown. Additionally, in non-lichenized fungi specific fatty acyl synthases (FASs) provide starters to the PKSs. Yet, the presence of such FASs in lichenized fungi remains to be investigated. Here we implement comparative genomics and metatranscriptomics to identify the most likely PKS and FASs for the synthesis of olivetoric and physodic acid, the primary depside and depsidone defining the two chemotypes of the lichen Pseudevernia furfuracea. We propose that the gene cluster PF33-1_006185, found in both chemotypes, is the most likely candidate for olivetoric and physodic acid biosynthesis. This is the first study to identify the gene cluster and the FAS likely responsible for physodic and olivetoric acid biosynthesis in a lichenized fungus. Our findings suggest that gene regulation and other epigenetic factors determine whether the mycobiont produces the depside or the depsidone, providing the first direct indication that chemotype diversity in lichens can arise through regulatory and not only through genetic diversity. Combining these results and existing literature, we propose a detailed scheme for depside/depsidone synthesis.

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A genome-wide screen identifies a single β-defensin gene cluster in the chicken: implications for the origin and evolution of mammalian defensins

BMC Genomics ◽

10.1186/1471-2164-5-56 ◽

2004 ◽

Vol 5 (1) ◽

Cited By ~ 200

Author(s):

Yanjing Xiao ◽

Austin L Hughes ◽

Junko Ando ◽

Yoichi Matsuda ◽

Jan-Fang Cheng ◽

...

Keyword(s):

Gene Cluster ◽

Origin And Evolution ◽

Defensin Gene ◽

Genome Wide ◽

A Genome

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Matrix metalloproteinase-degraded type I collagen is associated with APOE/TOMM40 variants and preclinical dementia

Neurology Genetics ◽

10.1212/nxg.0000000000000508 ◽

2020 ◽

Vol 6 (5) ◽

pp. e508

Author(s):

Man-Hung Eric Tang ◽

Joseph P.M. Blair ◽

Cecilie Liv Bager ◽

Anne-Christine Bay-Jensen ◽

Kim Henriksen ◽

...

Keyword(s):

Cognitive Impairment ◽

Matrix Metalloproteinase ◽

Gene Cluster ◽

Type I Collagen ◽

Early Death ◽

Collagen Metabolism ◽

Type I ◽

Age Related ◽

Genome Wide ◽

A Genome

ObjectiveDysregulation of type I collagen metabolism has a great impact on human health. We have previously seen that matrix metalloproteinase–degraded type I collagen (C1M) is associated with early death and age-related pathologies. To dissect the biological impact of type I collagen dysregulation, we have performed a genome-wide screening of the genetic factors related to type I collagen turnover.MethodsPatient registry data and genotypes have been collected for a total of 4,981 Danish postmenopausal women. Genome-wide association with serum levels of C1M was assessed and phenotype-genotype association analysis performed.ResultsTwenty-two genome-wide significant variants associated with C1M were identified in the APOE-C1/TOMM40 gene cluster. The APOE-C1/TOMM40 gene cluster is associated with hyperlipidemia and cognitive disorders, and we further found that C1M levels correlated with tau degradation markers and were decreased in women with preclinical cognitive impairment.ConclusionsOur study provides elements for better understanding the role of the collagen metabolism in the onset of cognitive impairment.

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Genome-Wide Studies in Sickle Cell Anemia Show Associations Between SNPs in the Olfactory Receptor Gene Cluster and Fetal Hemoglobin Concentration.

Blood ◽

10.1182/blood.v114.22.821.821 ◽

2009 ◽

Vol 114 (22) ◽

pp. 821-821 ◽

Cited By ~ 1

Author(s):

Nadia Timofeev ◽

Jacqueline N. Milton ◽

Stephen W Hartley ◽

Richard Sherva ◽

Paola Sebastiani ◽

...

Keyword(s):

Gene Cluster ◽

Olfactory Receptor ◽

Globin Gene ◽

Fetal Hemoglobin ◽

Call Rate ◽

Globin Gene Cluster ◽

Genome Wide ◽

A Genome ◽

Or Genes ◽

Genome Wide Significance

Abstract Abstract 821 Fetal hemoglobin (HbF) is the major modulator of sickle cell anemia (SCA, homozygosity for HBB glu6val) severity. In a genome-wide association study in African Americans with SCA we sought to identify single nucleotide polymorphisms (SNPs) associated with HbF concentrations. A discovery sample of 848 African American subjects and a primary replication study of 305 subjects were examined. DNA was genotyped with the Illumina Human610-Quad SNP; some replication set samples were genotyped with the Sentrix HumanCNV370 or the 317K array. For quality control we excluded SNPs with a call rate less than 95%; we excluded subjects with a call rate less than 93%; identity by descent measurements were computed to identify related individuals who were removed from analysis; we inferred gender using chromosome X SNPs removing subjects with gender mismatches; a genome-wide principal components analysis found no association between the phenotype and the first 10 principal components, indicating that the results were not affected by population substructure. The association between HbF and the genotype for each SNP was tested with a multiple linear regression analysis adjusting for sex and assuming an additive model using the software PLINK. SCA is a rare disease in developed countries and assembling large data sets is not feasible. Therefore, true associations with limited effect sizes might not reach “genome-wide” significance of 10-08. To identify genes enriched with moderately strong associations, we developed a SNP set enrichment analysis (SSEA) that computes the probability that a set of SNPs is selected as significant by chance and scores each gene by this probability. Two SNPs exceeded the strict genome-wide significance: SNP rs5006884 in a novel region on chromosome 11 upstream of the β-globin gene cluster locus control region (LCR) containing the olfactory receptor (OR) genes OR51B5 and OR51B6; SNP rs766432 in BCL11A, previously found to be associated with HbF in several different populations. Data for SNPs common to the discovery and replication sets were combined and analyzed jointly. Similarity of the regression beta coefficients across datasets and increased significance of the p-values compared with those observed in the analyses of individual datasets provide additional evidence that the associations were consistent in the both datasets. The Q-Q plot and a genomic inflation factor of 1.003 both suggest that the test statistics are not inflated and are distributed appropriately. SSEA identified 2 OR genes (OR51B5, OR51B6) and BCL11A as enriched in both the discovery and replication sets. The most significant SNP in the OR region (rs5006884) and BCL11A (rs766432) explained 15.6% of the variability in HbF. Also, in the interval Xp 22.2-22.3 we found moderate, but not “genome-wide” significance for 1 SNP in Xp22.2. Phylogenetic conservation of some OR genes and their flanking sequences suggests that this region might also have a role in controlling expression within the β-globin gene-like complex. Low linkage disequilibrium between SNPs in the β-globin locus and the OR genes suggests that one or more variants in the OR genes independently regulate HbF. The top SNP in the OR51B5/OR51B6 locus, rs5006884, was still associated with HbF (p = 1.5E-05) in a model adjusting both for sex and rs2071348, a SNP in tight LD with the HBG2 5' -158 C-T SNP, giving further evidence that the OR region provides important information in addition to the SNPs in the β-globin gene-like complex. Polymorphisms in the upstream OR region might conceivably modulate HbF levels by altering chromatin structure within the β-globin gene cluster. Conserved binding sites for the transcription factor CTCF flank the β-globin gene cluster and evidence suggests that these sites function as insulators. Polymorphisms in this region might affect the actions of enhancers, possibly through their effects on CTCF binding its receptors, thereby affecting the interaction of the globin genes with enhancers in the OR regions. Disclosures: No relevant conflicts of interest to declare.

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Genetic Variants Modifying the Triglycerides-Lowering Effect of Fish Oil Supplementation: A Genome-Wide Interaction Study

Current Developments in Nutrition ◽

10.1093/cdn/nzab050_006 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 939-939

Author(s):

Michael Francis ◽

Changwei Li ◽

Yitang Sun ◽

Jingqi Zhou ◽

Xiang Li ◽

...

Keyword(s):

Fish Oil ◽

Gene Cluster ◽

Genetic Variants ◽

Meta Analysis ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Interaction Study ◽

Genome Wide ◽

A Genome ◽

Fish Oil Supplementation

Abstract Objectives To identify genetic variants that modify the effect of fish oil supplementation on blood lipids, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. Methods We performed a genome-wide interaction study in 73,962 participants of European ancestry from the UK Biobank. Candidate associations were evaluated in a replication study with 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Meta-analysis was further performed across the two cohorts. Results Four novel interaction loci were identified at genome-wide significance in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A > G; minor allele frequency = 0.041), shows an interaction effect but not the main effect, suggesting that it would not have been discovered in a typical association study. Fish oil supplementation is associated with a decreased blood level of triglycerides in individuals carrying the minor allele, but with an increased level in homozygotes of the major allele. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue, while connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Conclusions Our study identifies novel interaction effects for four genetic loci and highlights genetic variants in the GJB6-GJB2-GJA3 gene cluster, which modify the effects of fish oil supplementation on lowering blood triglycerides. These findings highlight the need and possibility for personalized nutrition. Funding Sources The University of Georgia Research Foundation

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Faculty Opinions recommendation of A genome-wide screen identifies a single beta-defensin gene cluster in the chicken: implications for the origin and evolution of mammalian defensins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1020798.240465 ◽

2004 ◽

Author(s):

Tomas Ganz

Keyword(s):

Gene Cluster ◽

Origin And Evolution ◽

Defensin Gene ◽

Genome Wide ◽

A Genome

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Genome-Wide Mutagenesis Links Multiple Metabolic Pathways with Actinorhodin Production inStreptomyces coelicolor

Applied and Environmental Microbiology ◽

10.1128/aem.03005-18 ◽

2019 ◽

Vol 85 (7) ◽

Cited By ~ 6

Author(s):

Zhong Xu ◽

Yuanyuan Li ◽

Yemin Wang ◽

Zixin Deng ◽

Meifeng Tao

Keyword(s):

Metabolic Pathways ◽

Antibiotic Production ◽

Streptomyces Coelicolor ◽

Acid Biosynthesis ◽

Content Type ◽

Cellular Processes ◽

Genome Wide ◽

A Genome ◽

Wide Perspective ◽

Actinorhodin Production

ABSTRACTStreptomycesspecies are important antibiotic-producing organisms that tightly regulate their antibiotic production. Actinorhodin is a typical antibiotic produced by the model actinomyceteStreptomyces coelicolor. To discover the regulators of actinorhodin production, we constructed a library of 50,000 independent mutants with hyperactive Tn5transposase-based transposition systems. Five hundred fifty-one genes were found to influence actinorhodin production in 988 individual mutants. Genetic complementation suggested that most of the insertions (76%) were responsible for the changes in antibiotic production. Genes involved in diverse cellular processes such as amino acid biosynthesis, carbohydrate metabolism, cell wall homeostasis, and DNA metabolism affected actinorhodin production. Genome-wide mutagenesis can identify novel genes and pathways that impact antibiotic levels, potentially aiding in engineering strains to optimize the production of antibiotics inStreptomyces.IMPORTANCEPrevious studies have shown that various genes can influence antibiotic production inStreptomycesand that intercommunication between regulators can complicate antibiotic production. Therefore, to gain a better understanding of antibiotic regulation, a genome-wide perspective on genes that influence antibiotic production was needed. We searched for genes that affected production of the antibiotic actinorhodin using a genome-wide gene disruption system. We identified 551 genes that altered actinorhodin levels, and more than half of these genes were newly identified effectors. Some of these genes may be candidates for engineeringStreptomycesstrains to improve antibiotic production levels.

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