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Genetics, genomics and evolution of ergot alkaloid diversity.

Young CA, Schardl CL, Panaccione DG, Florea S, Takach JE, Charlton ND, Moore N, Webb JS, Jaromczyk J - Toxins (Basel) (2015)

Bottom Line: The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization.Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids.The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine.

View Article: PubMed Central - PubMed

Affiliation: Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK 73401, USA. cayoung@noble.org.

ABSTRACT
The ergot alkaloid biosynthesis system has become an excellent model to study evolutionary diversification of specialized (secondary) metabolites. This is a very diverse class of alkaloids with various neurotropic activities, produced by fungi in several orders of the phylum Ascomycota, including plant pathogens and protective plant symbionts in the family Clavicipitaceae. Results of comparative genomics and phylogenomic analyses reveal multiple examples of three evolutionary processes that have generated ergot-alkaloid diversity: gene gains, gene losses, and gene sequence changes that have led to altered substrates or product specificities of the enzymes that they encode (neofunctionalization). The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization. Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids. Genetic alterations associated with interspecific hybrids of Epichloë species suggest that such variation is also selectively favored. The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine.

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Related in: MedlinePlus

Gene map showing dmaW and easF paralogues in the region flanking the EAS locus from C. purpurea strain 20.1. The genes for recQ helicase and paralogues of dmaW and easF are shown in black, and the genes pertaining to the EAS cluster are color-coded based on position of the encoded step within the pathway. For other genes, the locus_tag names (GenBank) are CPUR_04108, CPUR_04107, etc., where only the last four digits are shown. Names of EAS genes are abbreviated as in Figure 2.
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toxins-07-01273-f011: Gene map showing dmaW and easF paralogues in the region flanking the EAS locus from C. purpurea strain 20.1. The genes for recQ helicase and paralogues of dmaW and easF are shown in black, and the genes pertaining to the EAS cluster are color-coded based on position of the encoded step within the pathway. For other genes, the locus_tag names (GenBank) are CPUR_04108, CPUR_04107, etc., where only the last four digits are shown. Names of EAS genes are abbreviated as in Figure 2.

Mentions: Although not by any means restricted to subtelomeric and subterminal regions, blocks of transposon-derived repeats are features of these genomic regions in fungi [65,66], and such regions are prone to considerable instability and gene duplication events [67,68]. A subterminal location appears to be the ancestral state of the EAS cluster, considering that it is a shared feature of N. fumigata and the basal EAS clade in Clavicipitaceae; namely, the clade comprised of the majority of Epichloë EAS clusters (Figure 3). Thus, increased stability, particularly of the EAS core containing early- and mid-pathway genes, seems to be in keeping with the shift from subterminal to internal location in the common ancestor of the crown EAS clade. Nevertheless, the differences in flanking housekeeping genes between the Claviceps subclade and the B. obtecta/At. hypoxylon subclade, plus indications of gene duplication in C. purpurea, indicate additional complexity in the history of the EAS clusters. In C. purpurea, the duplication of lpsA has enabled its neofunctionalization to greatly enhance the diversity of ergopeptine products (Figure 10). Interestingly, 55-73 kb downstream of lpsC in the C. purpurea genome are two additional copies of dmaW and easF (Figure 11), suggesting that gene duplication has been a particularly dynamic evolutionary process in C. purpurea in addition to providing an attractive explanation for the fact that most of the known ergopeptin(in)es are reported from this species. Furthermore, the dmaW and easF duplications are close to a recQ helicase pseudogene, and reflecting their typical locations, recQ helicase genes are also called telomere-linked helicase genes (TLH). (For example, a recQ helicase gene is located near the EAS-linked telomere of N. fumigata, as shown in Figure 2 and Figure 9). In C. purpurea, the association of a recQ helicase pseudogene with duplicated EAS genes and in the vicinity of the EAS cluster suggests more recent evolutionary history associated with a chromosome end than implied in our phylogenetic inferences (Figure 3). Thus, repeated shifts between subterminal and internal locations may have characterized EAS clusters in the Clavicipitaceae, and perhaps especially in C. purpurea as a driver of ergopeptine diversification.


Genetics, genomics and evolution of ergot alkaloid diversity.

Young CA, Schardl CL, Panaccione DG, Florea S, Takach JE, Charlton ND, Moore N, Webb JS, Jaromczyk J - Toxins (Basel) (2015)

Gene map showing dmaW and easF paralogues in the region flanking the EAS locus from C. purpurea strain 20.1. The genes for recQ helicase and paralogues of dmaW and easF are shown in black, and the genes pertaining to the EAS cluster are color-coded based on position of the encoded step within the pathway. For other genes, the locus_tag names (GenBank) are CPUR_04108, CPUR_04107, etc., where only the last four digits are shown. Names of EAS genes are abbreviated as in Figure 2.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417967&req=5

toxins-07-01273-f011: Gene map showing dmaW and easF paralogues in the region flanking the EAS locus from C. purpurea strain 20.1. The genes for recQ helicase and paralogues of dmaW and easF are shown in black, and the genes pertaining to the EAS cluster are color-coded based on position of the encoded step within the pathway. For other genes, the locus_tag names (GenBank) are CPUR_04108, CPUR_04107, etc., where only the last four digits are shown. Names of EAS genes are abbreviated as in Figure 2.
Mentions: Although not by any means restricted to subtelomeric and subterminal regions, blocks of transposon-derived repeats are features of these genomic regions in fungi [65,66], and such regions are prone to considerable instability and gene duplication events [67,68]. A subterminal location appears to be the ancestral state of the EAS cluster, considering that it is a shared feature of N. fumigata and the basal EAS clade in Clavicipitaceae; namely, the clade comprised of the majority of Epichloë EAS clusters (Figure 3). Thus, increased stability, particularly of the EAS core containing early- and mid-pathway genes, seems to be in keeping with the shift from subterminal to internal location in the common ancestor of the crown EAS clade. Nevertheless, the differences in flanking housekeeping genes between the Claviceps subclade and the B. obtecta/At. hypoxylon subclade, plus indications of gene duplication in C. purpurea, indicate additional complexity in the history of the EAS clusters. In C. purpurea, the duplication of lpsA has enabled its neofunctionalization to greatly enhance the diversity of ergopeptine products (Figure 10). Interestingly, 55-73 kb downstream of lpsC in the C. purpurea genome are two additional copies of dmaW and easF (Figure 11), suggesting that gene duplication has been a particularly dynamic evolutionary process in C. purpurea in addition to providing an attractive explanation for the fact that most of the known ergopeptin(in)es are reported from this species. Furthermore, the dmaW and easF duplications are close to a recQ helicase pseudogene, and reflecting their typical locations, recQ helicase genes are also called telomere-linked helicase genes (TLH). (For example, a recQ helicase gene is located near the EAS-linked telomere of N. fumigata, as shown in Figure 2 and Figure 9). In C. purpurea, the association of a recQ helicase pseudogene with duplicated EAS genes and in the vicinity of the EAS cluster suggests more recent evolutionary history associated with a chromosome end than implied in our phylogenetic inferences (Figure 3). Thus, repeated shifts between subterminal and internal locations may have characterized EAS clusters in the Clavicipitaceae, and perhaps especially in C. purpurea as a driver of ergopeptine diversification.

Bottom Line: The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization.Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids.The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine.

View Article: PubMed Central - PubMed

Affiliation: Forage Improvement Division, The Samuel Roberts Noble Foundation, Ardmore, OK 73401, USA. cayoung@noble.org.

ABSTRACT
The ergot alkaloid biosynthesis system has become an excellent model to study evolutionary diversification of specialized (secondary) metabolites. This is a very diverse class of alkaloids with various neurotropic activities, produced by fungi in several orders of the phylum Ascomycota, including plant pathogens and protective plant symbionts in the family Clavicipitaceae. Results of comparative genomics and phylogenomic analyses reveal multiple examples of three evolutionary processes that have generated ergot-alkaloid diversity: gene gains, gene losses, and gene sequence changes that have led to altered substrates or product specificities of the enzymes that they encode (neofunctionalization). The chromosome ends appear to be particularly effective engines for gene gains, losses and rearrangements, but not necessarily for neofunctionalization. Changes in gene expression could lead to accumulation of various pathway intermediates and affect levels of different ergot alkaloids. Genetic alterations associated with interspecific hybrids of Epichloë species suggest that such variation is also selectively favored. The huge structural diversity of ergot alkaloids probably represents adaptations to a wide variety of ecological situations by affecting the biological spectra and mechanisms of defense against herbivores, as evidenced by the diverse pharmacological effects of ergot alkaloids used in medicine.

Show MeSH
Related in: MedlinePlus