ArticleProceedings of the National Academy of Sciences of the United States of America2013
Physical linkage of metabolic genes in fungi is an adaptation against the accumulation of toxic intermediate compounds.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed.
- Generalized Gene Cluster Detection Using CLOCI.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Sticky enzymes: increased metabolic efficiency via substrate-dependent enzyme clustering.PRX life · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
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- The transcriptional coordination of functional gene clusters is dependent on multiple chromatin remodelers in a haploid strain of the budding yeast,Frontiers in fungal biology · 2025Article
- CLOCI: unveiling cryptic fungal gene clusters with generalized detection.Nucleic acids research · 2024Article
- Functional Crosstalk between Discrete Indole Terpenoid Gene Clusters inOrganic letters · 2023Article
- Mining for a new class of fungal natural products: the evolution, diversity, and distribution of isocyanide synthase biosynthetic gene clusters.Nucleic acids research · 2023Article
- Functional Clustering of Metabolically Related Genes Is Conserved acrossJournal of fungi (Basel, Switzerland) · 2023Review
- Mining for a New Class of Fungal Natural Products: The Evolution, Diversity, and Distribution of Isocyanide Synthase Biosynthetic Gene Clusters.bioRxiv : the preprint server for biology · 2023Article
- Metagenomics Shines Light on the Evolution of "Sunscreen" Pigment Metabolism in the Teloschistales (Lichen-Forming Ascomycota).Genome biology and evolution · 2023Article
- Contrasting modes of macro and microsynteny evolution in a eukaryotic subphylum.Current biology : CB · 2022Article
- Regulatory mechanisms ensuring coordinated expression of functionally related genes.Trends in genetics : TIG · 2022Review
- Linkage and association analyses reveal that hub genes in energy-flow and lipid biosynthesis pathways form a cluster in upland cotton.Computational and structural biotechnology journal · 2022Article
- The evolution of the GALactose utilization pathway in budding yeasts.Trends in genetics : TIG · 2022Review
- Mining genomes to illuminate the specialized chemistry of life.Nature reviews. Genetics · 2021Review
- Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway.Open biology · 2021Article
- Acyltransferase AniI, a Tailoring Enzyme with Broad Substrate Tolerance for High-Level Production of Anisomycin.Applied and environmental microbiology · 2021Article
- Widespread polycistronic gene expression in green algae.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Colocality to Cofunctionality: Eukaryotic Gene Neighborhoods as a Resource for Function Discovery.Molecular biology and evolution · 2021Article
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3 authors.
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Abstract
Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s) favored by selection, resulting in cluster formation and maintenance, has not been forthcoming. We noted that the cause of certain well-studied human metabolic disorders is the accumulation of toxic intermediate compounds (ICs), which occurs when the product of an enzyme is not used as a substrate by a downstream neighbor in the metabolic network. This raises the hypothesis that the phenotype favored by selection to drive gene clustering is the mitigation of IC toxicity. To test this, we examined 100 diverse fungal genomes for the simplest type of cluster, gene pairs that are both metabolic neighbors and chromosomal neighbors immediately adjacent to each other, which we refer to as "double neighbor gene pairs" (DNGPs). Examination of the toxicity of their corresponding ICs shows that, compared with chromosomally nonadjacent metabolic neighbors, DNGPs are enriched for ICs that have acutely toxic LD50 doses or reactive functional groups. Furthermore, DNGPs are significantly more likely to be divergently oriented on the chromosome; remarkably, ∼40% of these DNGPs have ICs known to be toxic. We submit that the structure of synteny in metabolic pathways of fungi is a signature of selection for protection against the accumulation of toxic metabolic intermediates.
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