Translational selection on codon usage in the genus Aspergillus

Iriarte, Andrés; Sanguinetti, Manuel; Fernández-Calero, Tamara; Naya, Hugo; Ramón, Ana; Musto, Héctor

doi:10.1016/j.gene.2012.06.027

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…The insertion of glutamine would restore the wild-type amino acid to allantoinase (Alx), but for the other two mutated proteins there would be a substitution of glutamine for tryptophan in AlcR and glutamine for serine in AreA600, which are presumably non-functional. There are 174 tRNAs annotated (Iriarte et al 2012), and of these seven are glutamine tRNAs. There are two glutamine tRNAs that recognize the codon CAA and five that recognize the preferred codon CAG (Lloyd and Sharp 1991; Iriarte et al 2012).…”

Section: Resultsmentioning

confidence: 99%

“…There are 174 tRNAs annotated (Iriarte et al 2012), and of these seven are glutamine tRNAs. There are two glutamine tRNAs that recognize the codon CAA and five that recognize the preferred codon CAG (Lloyd and Sharp 1991; Iriarte et al 2012). The suppressor tRNAs that have been selected independently ( suaB111 , suaD103 , and suaD108 ) are all in tRNAs that recognize CAG codons.…”

Section: Resultsmentioning

confidence: 99%

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InAspergillus nidulansthe SuppressorssuaAandsuaCCode for Release Factors eRF1 and eRF3 andsuaDCodes for a Glutamine tRNA

Liu

Mellado

Espeso

et al. 2014

G3 Genes|Genomes|Genetics

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In Aspergillus nidulans, after extensive mutagenesis, a collection of mutants was obtained and four suppressor loci were identified genetically that could suppress mutations in putative chain termination mutations in different genes. Suppressor mutations in suaB and suaD have a similar restricted spectrum of suppression and suaB111 was previously shown to be an alteration in the anticodon of a gln tRNA. We have shown that like suaB, a suaD suppressor has a mutation in the anticodon of another gln tRNA allowing suppression of UAG mutations. Mutations in suaA and suaC had a broad spectrum of suppression. Four suaA mutations result in alterations in the coding region of the eukaryotic release factor, eRF1, and another suaA mutation has a mutation in the upstream region of eRF1 that prevents splicing of the first intron within the 5′UTR. Epitope tagging of eRF1 in this mutant results in 20% of the level of eRF1 compared to the wild-type. Two mutations in suaC result in alterations in the eukaryotic release factor, eRF3. This is the first description in Aspergillus nidulans of an alteration in eRF3 leading to suppression of chain termination mutations.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

InAspergillus nidulansthe SuppressorssuaAandsuaCCode for Release Factors eRF1 and eRF3 andsuaDCodes for a Glutamine tRNA

Liu

Mellado

Espeso

et al. 2014

G3 Genes|Genomes|Genetics

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“…In addition to removal of introns, the synthetic C. africana cloA allele differed from the native allele in two other ways, (i) a gpdA promoter from N. fumigata was used on the synthetic allele, whereas an N. fumigata easA promoter drove expression of the native allele, and (ii) codon usage was altered in the synthetic allele to conform with preferences observed in N. fumigata (28) without altering the protein sequence. These changes might affect the quantity of DHLA produced; however; the qualitative presence/absence of DHLA observed almost certainly resulted from the production of a full-length protein.…”

Section: Discussionmentioning

confidence: 99%

“…KY681814) was derived from the C. africana allele by deleting introns (as marked in Fig. S3 in the supplemental material) and changing nucleotides to favor codons considered optimal for N. fumigata in the analyses of Iriarte et al (28) without altering amino acid sequence of the product (see Fig. S4).…”

Section: Modification Of Fungimentioning

confidence: 99%

Biosynthesis of the Pharmaceutically Important Fungal Ergot Alkaloid Dihydrolysergic Acid Requires a Specialized Allele of cloA

Arnold

Panaccione

2017

Appl Environ Microbiol

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Ergot alkaloids are specialized fungal metabolites that are important as the bases of several pharmaceuticals. Many ergot alkaloids are derivatives of lysergic acid (LA) and have vasoconstrictive activity, whereas several dihydrolysergic acid (DHLA) derivatives are vasorelaxant. The pathway to LA is established, with the P450 monooxygenase CloA playing a key role in oxidizing its substrate agroclavine to LA. We analyzed the activities of products of cloA alleles from different fungi relative to DHLA biosynthesis by expressing them in a mutant of the fungus Neosartorya fumigata that accumulates festuclavine, the precursor to DHLA. Transformants expressing CloA from Epichloë typhina ϫ Epichloë festucae, which oxidizes agroclavine to LA, failed to oxidize festuclavine to DHLA. In substrate feeding experiments, these same transformants oxidized exogenously supplied agroclavine to LA, indicating that a functional CloA was produced. A genomic clone of cloA from Claviceps africana, a sorghum ergot fungus that produces a DHLA derivative, was cloned and expressed in the festuclavine-accumulating mutant of N. fumigata, but several introns in this genomic clone were not processed properly. Expression of a synthetic intron-free version of C. africana cloA resulted in the accumulation of DHLA as assessed by fluorescence high-pressure liquid chromatography (HPLC) and liquid chromatographymass spectrometry (LC-MS). In substrate feeding experiments, the C. africana CloA also accepted agroclavine as the substrate, oxidizing it to LA. The data indicate that a specialized allele of cloA is required for DHLA biosynthesis and that the pharmaceutically important compound DHLA can be produced in engineered N. fumigata. IMPORTANCE Ergot alkaloids are fungal metabolites that have impacted humankind historically as poisons and more recently as pharmaceuticals used to treat dementia, migraines, and other disorders. Much is known about the biosynthesis of ergot alkaloids that are derived from lysergic acid (LA), but important questions remain about a parallel pathway to ergot alkaloids derived from dihydrolysergic acid (DHLA). DHLA-derived alkaloids have minor structural differences compared to LA-derived alkaloids but can have very different activities. To understand how DHLA is made, we analyzed activities of a key enzyme in the DHLA pathway and found that it differed from its counterpart in the LA pathway. Our data indicate a critical difference between the two pathways and provide a strategy for producing DHLA by modifying a model fungus. The ability to produce DHLA in a model fungus may facilitate synthesis of DHLA-derived pharmaceuticals.KEYWORDS ergot alkaloids, lysergic acid, dihydrolysergic acid, P450 monooxygenase E rgot alkaloids are specialized fungal metabolites that have impacted humankind historically as toxins and more recently as pharmaceuticals used to treat dementia, migraines, hyperprolactinemia, and Parkinson's disease (1-4). Many natural ergot alka-

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“…In an analysis of 100 eubacterial and archaeal genomes, authors found that genome-wide codon usage bias was primarily driven by mutational pressure that acts throughout the genome, and secondarily by selective forces acting on translated sequences (Chen et al, 2004). In Aspergillus , mutation pressure influences codon usage bias in low-expression genes, and selection driven codon usage bias in high-expression genes (Lloyd and Sharp, 1991; Iriarte et al, 2012). In addition, codon usage bias plays an important role in gene expression.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Codon Usage Bias in Seven Epichloë Species and Their Peramine-Coding Genes

et al. 2017

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Codon usage bias plays an important role in shaping genomes and genes in unicellular species and multicellular species. Here, we first analyzed codon usage bias in seven Epichloë species and their peramine-coding genes. Our results showed that both natural selection and mutation pressure played a role in forming codon usage bias in seven Epichloë species. All seven Epichloë species contained a peramine-coding gene cluster. Interestingly, codon usage bias of peramine-coding genes were not affected by natural selection or mutation pressure. There were 13 codons more frequently found in Epichloë genome sequences, peramine-coding gene clusters and orthologous peramine-coding genes, all of which had a bias to end with a C nucleotide. In the seven genomes analyzed, codon usage was biased in highly expressed coding sequences (CDSs) with shorter length and higher GC content. Genes in the peramine-coding gene cluster had higher GC content at the third nucleotide position of the codon, and highly expressed genes had higher GC content at the second position. In orthologous peramine-coding CDSs, high expression level was not significantly correlated with CDS length and GC content. Analysis of selection pressure identified that the genes orthologous to peramine genes were under purifying selection. There were no differences in codon usage bias and selection pressure between peramine product genes and non-functional peramine product genes. Our results provide insights into understanding codon evolution in Epichloë species.

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Translational selection on codon usage in the genus Aspergillus

Cited by 21 publications

References 36 publications

InAspergillus nidulansthe SuppressorssuaAandsuaCCode for Release Factors eRF1 and eRF3 andsuaDCodes for a Glutamine tRNA

InAspergillus nidulansthe SuppressorssuaAandsuaCCode for Release Factors eRF1 and eRF3 andsuaDCodes for a Glutamine tRNA

Biosynthesis of the Pharmaceutically Important Fungal Ergot Alkaloid Dihydrolysergic Acid Requires a Specialized Allele of cloA

Comprehensive Analysis of Codon Usage Bias in Seven Epichloë Species and Their Peramine-Coding Genes

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