Dataset Information

Genetics, genomics and evolution of ergot alkaloid diversity.

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.

SUBMITTER: Young CA

PROVIDER: S-EPMC4417967 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetics, genomics and evolution of ergot alkaloid diversity.

Young Carolyn A CA Schardl Christopher L CL Panaccione Daniel G DG Florea Simona S Takach Johanna E JE Charlton Nikki D ND Moore Neil N Webb Jennifer S JS Jaromczyk Jolanta J

Toxins 20150414 4

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 ...[more]

PMID: 25875294

Similar Datasets

Project description:Pregnant Suffolk ewes (n = 19; 81.2kg ± 7.7) estimated to be carrying twins were assigned to endophyte-infected tall fescue seed (E+; 4.14 µg ergovaline + ergovalinine/g seed) or a control diet (CON; 0 µg ergovaline + ergovalinine) and evaluated at different stages of gestation (gd85 [pre-treatment, n = 3], gd110 [n = 4/treatment] or gd133 [n = 4/treatment). Ewes were individually fed a basal diet with (E+) or without (CON) endophyte-infected tall fescue seed from gd86 to gd110 or gd133. A terminal necropsy was performed, and uterine components were evaluated for size, weight, and type. Data were analyzed using a priori contrasts to test effects of stage of gestation (gd85 vs. gd110 or gd110 vs. gd133) and adaptive responses to feeding E+ fescue seed versus CON at gd110 and gd133. Serum prolactin concentrations were greater (P < 0.05) at gd110 than gd85, and then remained constant to gd133. Feeding E+ tall fescue seed reduced (P < 0.05) serum prolactin concentrations compared to CON at both gd110 and gd133. From gd85 to gd110, placentome type and number changed from type A to type B (P < 0.05) but did not change (P > 0.05) after gd110. Total fetal weight per ewe increased 2977 g from gd85 to gd110 (P = 0.011) and then 3151 g from gd110 to 133 (P = 0.012). Brain weight as a percentage of fetal body weight was higher (P = 0.029) for E+ fetuses on gd110 compared to CON, which demonstrates asymmetrical growth and intrauterine growth restriction (IUGR). In total, 15,961 genes were identified in the cotyledon through mapping to the ovine genome across all samples. There were 136 genes differentially expressed (FDR < 0.05; log2foldchange < -1 and > 1) from gd85 to gd110 with ovarian steroidogenesis and steroid biosynthesis pathways enriched and 469 genes differentially expressed from gd110 to gd133 with ribosome and oxidative phosphorylation pathways enriched. Exposure to E+ fescue resulted in differential expression of 22 genes at gd110 but only one gene at gd133 compared to CON. These results show that there are major changes in fetal growth and placental remodeling during the late gestation period that are influenced by exposure to ergot alkaloids from endophyte-infected tall fescue seed; however, major changes in the transcriptome of the cotyledon tissue in response to E+ fescue were not observed and other factors must be involved in the reduction of placental efficiency and fetal growth observed with E+ fescue exposure.

Project description:Ergot alkaloids are specialized fungal metabolites with potent biological activities. They are encoded by well-characterized gene clusters in the genomes of producing fungi. Penicillium camemberti plays a major role in the ripening of Brie and Camembert cheeses. The P. camemberti genome contains a cluster of five genes shown in other fungi to be required for synthesis of the important ergot alkaloid intermediate chanoclavine-I aldehyde and two additional genes (easH and easQ) that may control modification of chanoclavine-I aldehyde into other ergot alkaloids. We analyzed samples of Brie and Camembert cheeses, as well as cultures of P. camemberti, and did not detect chanoclavine-I aldehyde or its derivatives. To create a functioning facsimile of the P. camembertieas cluster, we expressed P. camemberti easH and easQ in a chanoclavine-I aldehyde-accumulating easA knockout mutant of Neosartorya fumigata The easH-easQ-engineered N. fumigata strain accumulated a pair of compounds of m/z 269.1288 in positive-mode liquid chromatography-mass spectrometry (LC-MS). The analytes fragmented in a manner typical of the stereoisomeric ergot alkaloids rugulovasine A and B, and the related rugulovasine producer Penicillium biforme accumulated the same isomeric pair of analytes. The P. camemberti eas genes were transcribed in culture, but comparison of the P. camemberti eas cluster with the functional cluster from P. biforme indicated 11 polymorphisms. Whereas other P. camembertieas genes functioned when expressed in N. fumigata, P. camembertieasC did not restore ergot alkaloids when expressed in an easC mutant. The data indicate that P. camemberti formerly had the capacity to produce the ergot alkaloids rugulovasine A and B.IMPORTANCE The presence of ergot alkaloid synthesis genes in the genome of Penicillium camemberti is significant, because the fungus is widely consumed in Brie and Camembert cheeses. Our results show that, although the fungus has several functional genes from the ergot alkaloid pathway, it produces only an early pathway intermediate in culture and does not produce ergot alkaloids in cheese. Penicillium biforme, a close relative of P. camemberti, contains a similar but fully functional set of ergot alkaloid synthesis genes and produces ergot alkaloids chanoclavine-I, chanoclavine-I aldehyde, and rugulovasine A and B. Our reconstruction of the P. camemberti pathway in the model fungus Neosartorya fumigata indicated that P. camemberti formerly had the capacity to produce these same ergot alkaloids. Neither P. camemberti nor P. biforme produced ergot alkaloids in cheese, indicating that nutritionally driven gene regulation prevents these fungi from producing ergot alkaloids in a dairy environment.

Project description:Previous research has shown that livestock exposed to ergot alkaloids results in decreased vasoactivity of gastrointestinal and peripheral vasculature. Little is known regarding the effect ergot alkaloid exposure during gestation may have on vasculature supporting the fetus. The objective of this study was to evaluate contractile responses of uterine and umbilical arteries collected from ewes consuming ergot alkaloids during gestation. On day 35 of gestation, 36 Suffolk ewes (78.24 ± 9.5 kg) were assigned to endophyte-infected (E+) or endophyte-free (E-) tall fescue seed treatments that were fed either throughout or switched on day 86 of gestation, creating four seed treatments E+E+, E+E-, E-E+, and E-E-. Ewes were fed E+ tall fescue seed to provide 1.77 mg of total ergovaline ⋅ hd-1 ⋅ d-1 with E- ewes receiving the same quantity of E- seed. Gestation was terminated on day 133, and sections of uterine artery and umbilical cord were surgically collected. Only collections from 28 ewes (n = 7/treatment) were of sufficient viability to proceed with the contractility experiments. Arteries were cleaned, sliced into 2-mm cross sections, and suspended in multi-myograph chambers containing 5 mL of continuously oxygenated Krebs-Henseleit buffer. Vessels were exposed to increasing concentrations (5 × 10-8 to 1 × 10-4 M) of norepinephrine, serotonin, ergotamine, and ergovaline (5 × 10-9 to 1 × 10-5M; extract of tall fescue seed) in 15-min intervals. Increasing concentrations of norepinephrine generated a contractile response by the uterine artery (P < 0.05), but no response in the umbilical artery. Increasing concentrations of serotonin resulted in negligible responses in uterine preparations, whereas umbilical artery preparations were responsive (P < 0.05) to serotonin. Ewes receiving E+E+ and E-E+ treatments had decreased vasoactivity in umbilical arteries to serotonin with a dextral shift in concentrations where the response curve initiated (P < 0.05). Interestingly, uterine arteries were not responsive to exposure to ergotamine or ergovaline, whereas umbilical arteries were responsive (P < 0.05). Umbilical arteries collected from ewes receiving E-E- and E+E- were more vasoactive to ergot alkaloids (P < 0.05) than other treatments. These findings indicate that maternal blood supply to the placenta appears protected from negative effects of ergot alkaloids; however, umbilical vasculature is not, and this could adversely influence fetal growth.

Dataset Information

Genetics, genomics and evolution of ergot alkaloid diversity.

Publications

Genetics, genomics and evolution of ergot alkaloid diversity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure