#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci


The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.


Vyšlo v časopise: Plant-Symbiotic Fungi as Chemical Engineers: Multi-Genome Analysis of the Clavicipitaceae Reveals Dynamics of Alkaloid Loci. PLoS Genet 9(2): e32767. doi:10.1371/journal.pgen.1003323
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003323

Souhrn

The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloë and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some—including the infamous ergot alkaloids—have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.


Zdroje

1. Wink M (2000) Interference of alkaloids with neuroreceptors and ion channels. In: Atta-ur-Rahman, editor. Bioactive Natural Products (Part B): Elsevier. pp. 3–122.

2. PažoutováS, OlšovskáJ, LinkaM, KolínskáR, FliegerM (2000) Chemoraces and habitat specialization of Claviceps purpurea populations. Appl Environ Microbiol 66: 5419–5425.

3. UhligS, BothaCJ, VrålstadT, RolénE, MilesCO (2009) Indole-diterpenes and ergot alkaloids in Cynodon dactylon (Bermuda grass) infected with Claviceps cynodontis from an outbreak of tremors in cattle. J Agric Food Chem 57: 11112–11119.

4. SchardlCL, LeuchtmannA, SpieringMJ (2004) Symbioses of grasses with seedborne fungal endophytes. Annu Rev Plant Biol 55: 315–340.

5. IannoneLJ, NovasMaV, YoungCA, De BattistaJP, SchardlCL (2012) Endophytes of native grasses from South America: Biodiversity and ecology. Fungal Ecology 5: 357–363.

6. SpataforaJW, SungGH, SungJM, Hywel-JonesNL, WhiteJF (2007) Phylogenetic evidence for an animal pathogen origin of ergot and the grass endophytes. Mol Ecol 16: 1701–1711.

7. SchardlCL, PanaccioneDG, TudzynskiP (2006) Ergot alkaloids–biology and molecular biology. Alkaloids Chem Biol 63: 45–86.

8. ClayK, SchardlC (2002) Evolutionary origins and ecological consequences of endophyte symbiosis with grasses. Am Nat 160: S99–S127.

9. SteinerU, LeibnerS, SchardlCL, LeuchtmannA, LeistnerE (2011) Periglandula, a new fungal genus within the Clavicipitaceae and its association with Convolvulaceae. Mycologia 103: 1133–1145.

10. RudgersJA, KoslowJM, ClayK (2004) Endophytic fungi alter relationships between diversity and ecosystem properties. Ecol Lett 7: 42–51.

11. MalinowskiDP, BeleskyDP (2000) Adaptations of endophyte-infected cool-season grasses to environmental stresses: Mechanisms of drought and mineral stress tolerance. Crop Sci 40: 923–940.

12. TudzynskiP, CorreiaT, KellerU (2001) Biotechnology and genetics of ergot alkaloids. Appl Microbiol Biotechnol 57: 593–605.

13. WiesemullerW (2005) Present and historical significance of ergot. Ernährungs Umschau 52: 147–148.

14. GigerRKA, EngelG (2006) Albert Hofmann's pioneering work on ergot alkaloids and its impact on the search of novel drugs at Sandoz, a predecessor company of Novartis. CHIMIA International Journal for Chemistry 60: 83–87.

15. SchardlCL, GrossmanRB, NagabhyruP, FaulknerJR, MallikUP (2007) Loline alkaloids: currencies of mutualism. Phytochemistry 68: 980–996.

16. TanakaA, TapperBA, PopayA, ParkerEJ, ScottB (2005) A symbiosis expressed non-ribosomal peptide synthetase from a mutualistic fungal endophyte of perennial ryegrass confers protection to the symbiotum from insect herbivory. Mol Microbiol 57: 1036–1050.

17. BacettyAA, SnookME, GlennAE, NoeJP, HillN, et al. (2009) Toxicity of endophyte-infected tall fescue alkaloids and grass metabolites on Pratylenchus scribneri. Phytopathology 99: 1336–1345.

18. BoutonJH, LatchGCM, HillNS, HovelandCS, McCannMA, et al. (2002) Reinfection of tall fescue cultivars with non-ergot alkaloid-producing endophytes. Agron J 94: 567–574.

19. LyonsPC, PlattnerRD, BaconCW (1986) Occurrence of peptide and clavine ergot alkaloids in tall fescue grass. Science 232: 487–489.

20. GallagherRT, HawkesAD, SteynPS, VleggaarR (1984) Tremorgenic neurotoxins from perennial ryegrass causing ryegrass staggers disorder of livestock: structure elucidation of lolitrem B. J Chem Soc Chem Commun 1984: 614–616.

21. MarkertA, SteffanN, PlossK, HellwigS, SteinerU, et al. (2008) Biosynthesis and accumulation of ergoline alkaloids in a mutualistic association between Ipomoea asarifolia (Convolvulaceae) and a clavicipitalean fungus. Plant Physiol 147: 296–305.

22. Tor-AgbidyeJ, BlytheLL, CraigAM (2001) Correlation of endophyte toxins (ergovaline and lolitrem B) with clinical disease: fescue foot and perennial ryegrass staggers. Vet Hum Toxicol 43: 140–146.

23. ThompsonRW, FribourgHA, WallerJC, SandersWL, ReynoldsJH, et al. (1993) Combined analysis of tall fescue steer grazing studies in the eastern United States. J Anim Sci 71: 1940–1946.

24. SchardlCL, YoungCA, FaulknerJR, FloreaS, PanJ (2012) Chemotypic diversity of epichloae, fungal symbionts of grasses. Fungal Ecol 5: 331–344.

25. SchardlCL (2010) The epichloae, symbionts of the grass subfamily Poöideae. Ann Mo Bot Gard 97: 646–665.

26. ZhangD-X, NagabhyruP, BlankenshipJD, SchardlCL (2010) Are loline alkaloid levels regulated in grass endophytes by gene expression or substrate availability? Plant Signal Behav 5: 1419–1422.

27. LeuchtmannA, SchmidtD, BushLP (2000) Different levels of protective alkaloids in grasses with stroma-forming and seed-transmitted Epichloë/Neotyphodium endophytes. J Chem Ecol 26: 1025–1036.

28. SaariS, HelanderM, LehtonenP, WalliusE, SaikkonenK (2010) Fungal endophytes reduce regrowth and affect competitiveness of meadow fescue in early succession of pastures. Grass and Forage Science 65: 287–295.

29. AfkhamiME, RudgersJA (2009) Endophyte-mediated resistance to herbivores depends on herbivore identity in the wild grass Festuca subverticillata. Environ Entomol 38: 1086–1095.

30. CrosignaniPG (2006) Current treatment issues in female hyperprolactinaemia. Eur J Obstet Gynecol Reprod Biol 125: 152–164.

31. Nichols DE (2001) LSD and its lysergamide cousins. The Heffter Review of Psychedelic Research. Santa Fe, New Mexico: Heffter Research Institute. pp. 80–87.

32. EadieMJ (2003) Convulsive ergotism: epidemics of the serotonin syndrome? Lancet Neurol 2: 429–434.

33. CaporaelLR (1976) Ergotism: the Satan loosed in Salem? Science 192: 21–26.

34. ScottP (2009) Ergot alkaloids: extent of human and animal exposure. World Mycotoxin Journal 2: 141–149.

35. UrgaK, DebellaA, W'MedihnY, NA, BayuA, et al. (2002) Laboratory studies on the outbreak of gangrenous ergotism associated with consumption of contaminated barley in Arsi, Ethiopia. Ethiopian Journal of Health and Development 16: 317–323.

36. SmithMM, WarrenVA, ThomasBS, BrochuRM, ErtelEA, et al. (2000) Nodulisporic acid opens insect glutamate-gated chloride channels: identification of a new high affinity modulator. Biochemistry 39: 5543–5554.

37. KnausHG, McManusOB, LeeSH, SchmalhoferWA, Garcia-CalvoM, et al. (1994) Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry 33: 5819–5828.

38. YoungC, McMillanL, TelferE, ScottB (2001) Molecular cloning and genetic analysis of an indole-diterpene gene cluster from Penicillium paxilli. Mol Microbiol 39: 754–764.

39. TsaiH-F, WangH, GeblerJC, PoulterCD, SchardlCL (1995) The Claviceps purpurea gene encoding dimethylallyltryptophan synthase, the committed step for ergot alkaloid biosynthesis. Biochem Biophys Res Commun 216: 119–125.

40. SpieringMJ, WilkinsonHH, BlankenshipJD, SchardlCL (2002) Expressed sequence tags and genes associated with loline alkaloid expression by the fungal endophyte Neotyphodium uncinatum. Fungal Genet Biol 36: 242–254.

41. LorenzN, HaarmannT, PažoutováS, JungM, TudzynskiP (2009) The ergot alkaloid gene cluster: Functional analyses and evolutionary aspects. Phytochemistry 70: 1822–1832.

42. SpieringMJ, MoonCD, WilkinsonHH, SchardlCL (2005) Gene clusters for insecticidal loline alkaloids in the grass-endophytic fungus Neotyphodium uncinatum. Genetics 169: 1403–1414.

43. YoungCA, FelittiS, ShieldsK, SpangenbergG, JohnsonRD, et al. (2006) A complex gene cluster for indole-diterpene biosynthesis in the grass endophyte Neotyphodium lolii. Fungal Genet Biol 43: 679–693.

44. SungGH, SungJM, Hywel JonesNL, SpataforaJW (2007) A multi-gene phylogeny of Clavicipitaceae (Ascomycota, Fungi): Identification of localized incongruence using a combinational bootstrap approach. Mol Phylogenet Evol 44: 1204–1223.

45. TanakaE, TanakaC (2008) Phylogenetic study of clavicipitaceous fungi using acetaldehyde dehydrogenase gene sequences. Mycoscience 49: 115–125.

46. GaoQ, JinK, YingS-H, ZhangY, XiaoG, et al. (2011) Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum. PLoS Genet 7: e1001264 doi:10.1371/journal.pgen.1001264

47. Pava-RipollM, AngeliniC, FangW, WangS, PosadaFJ, et al. (2011) The rhizosphere-competent entomopathogen Metarhizium anisopliae expresses a specific subset of genes in plant root exudate. Microbiology 157: 47–55.

48. FleetwoodDJ, ScottB, LaneGA, TanakaA, JohnsonRD (2007) A complex ergovaline gene cluster in epichloë endophytes of grasses. Appl Environ Microbiol 73: 2571–2579.

49. SteinerU, LeistnerE (2012) Ergoline alkaloids in convolvulaceous host plants originate from epibiotic clavicipitaceous fungi of the genus Periglandula. Fungal Ecol 5: 316–321.

50. Gröger D, Floss HG (1998) Biochemistry of ergot alkaloids – achievements and challenges. In: Cordell GA, editor. Alkaloids Chem Biol. New York: Academic Press. pp. 171–218.

51. HaarmannT, LorenzN, TudzynskiP (2008) Use of a nonhomologous end joining deficient strain (Δku70) of the ergot fungus Claviceps purpurea for identification of a nonribosomal peptide synthetase gene involved in ergotamine biosynthesis. Fungal Genet Biol 45: 35–44.

52. CastagnoliNJr, CorbettK, ChainEB, ThomasR (1970) Biosynthesis of N-(α-hydroxyethyl) lysergamide, a metabolite of Claviceps paspali Stevens and Hall. Biochem J 117: 451–455.

53. SaikiaS, TakemotoD, TapperBA, LaneGA, FrazerK, et al. (2012) Functional analysis of an indole-diterpene gene cluster for lolitrem B biosynthesis in the grass endosymbiont Epichloë festucae. FEBS Lett (in press)..

54. ColeRJ, DornerJW, LansdenJA, CoxRH, PapeC, et al. (1977) Paspalum staggers: isolation and identification of tremorgenic metabolites from sclerotia of Claviceps paspali. J Agric Food Chem 25: 1197–1201.

55. LiSM, UnsoldIA (2006) Post-genome research on the biosynthesis of ergot alkaloids. Planta Med 72: 1117–1120.

56. SaikiaS, ParkerEJ, KoulmanA, ScottB (2007) Defining paxilline biosynthesis in Penicillium paxilli: functional characterization of two cytochrome P450 monooxygenases. J Biol Chem 282: 16829–16837.

57. EatonCJ, CoxMP, AmbroseB, BeckerM, HesseU, et al. (2010) Disruption of signaling in a fungal-grass symbiosis leads to pathogenesis. Plant Physiology 153: 1780–1794.

58. TusnádyGE, SimonI (2001) The HMMTOP transmembrane topology prediction server. Bioinformatics 17: 849–850.

59. KroghA, LarssonBr, von HeijneG, SonnhammerELL (2001) Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305: 567–580.

60. MasamiI, MasafumiA, DemeloML, ToshioS (2002) Transmembrane topology prediction methods: a re-assessment and improvement by a consensus method using a dataset of experimentally-characterized transmembrane topologies. In Silico Biol 2: 19–33.

61. SaikiaS, ParkerEJ, KoulmanA, ScottB (2006) Four gene products are required for the fungal synthesis of the indole-diterpene, paspaline. FEBS Lett 580: 1625–1630.

62. KutilBL, GreenwaldC, LiuG, SpieringMJ, SchardlCL, et al. (2007) Comparison of loline alkaloid gene clusters across fungal endophytes: Predicting the co-regulatory sequence motifs and the evolutionary history. Fungal Genet Biol 44: 1002–1010.

63. GaoWM, KhangCH, ParkSY, LeeYH, KangSC (2002) Evolution and organization of a highly dynamic, subtelomeric helicase gene family in the rice blast fungus Magnaporthe grisea. Genetics 162: 103–112.

64. CuomoCA, GuldenerU, XuJ-R, TrailF, TurgeonBG, et al. (2007) The Fusarium graminearum genome reveals a link between localized polymorphism and pathogen specialization. Science 317: 1400–1402.

65. ClutterbuckAJ (2011) Genomic evidence of repeat-induced point mutation (RIP) in filamentous ascomycetes. Fungal Genet Biol 48: 306–326.

66. FreitagM, WilliamsRL, KotheGO, SelkerEU (2002) A cytosine methyltransferase homologue is essential for repeat-induced point mutation in Neurospora crassa. Proc Natl Acad Sci U S A 99: 8802–8807.

67. FleetwoodDJ, KhanAK, JohnsonRD, YoungCA, MittalS, et al. (2011) Abundant degenerate miniature inverted-repeat transposable elements in genomes of epichloid fungal endophytes of grasses. Genome Biol Evol 3: 1253–1264.

68. PhilippiT, SegerJ (1989) Hedging one's evolutionary bets, revisited. Trends Ecol Evol 4: 41–44.

69. SvardalH, RuefflerC, HermissonJ (2011) Comparing environmental and genetic variance as adaptive response to fluctuating selection. Evolution 65: 2492–2513.

70. LorenzN, WilsonEV, MachadoC, SchardlCL, TudzynskiP (2007) Comparison of ergot alkaloid biosynthesis gene clusters in Claviceps species indicates loss of late pathway steps in evolution of C. fusiformis. Appl Environ Microbiol 73: 7185–7191.

71. YoungC, BryantM, ChristensenM, TapperB, BryanG, et al. (2005) Molecular cloning and genetic analysis of a symbiosis-expressed gene cluster for lolitrem biosynthesis from a mutualistic endophyte of perennial ryegrass. Mol Genet Genomics 274: 13–29.

72. SpieringMJ, FaulknerJR, ZhangD-X, MachadoC, GrossmanRB, et al. (2008) Role of the LolP cytochrome P450 monooxygenase in loline alkaloid biosynthesis. Fungal Genet Biol 45: 1307–1314.

73. BlaneyBJ, MaryamR, MurrayS-A, RyleyMJ (2003) Alkaloids of the sorghum ergot pathogen (Claviceps africana): assay methods for grain and feed and variation between sclerotia/sphacelia. Aust J Agric Res 54: 167–175.

74. CoyleCM, ChengJZ, O'ConnorSE, PanaccioneDG (2010) An old yellow enzyme gene controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways. Appl Environ Microbiol 76: 3898–3903.

75. HaarmannT, OrtelI, TudzynskiP, KellerU (2006) Identification of the cytochrome P450 monooxygenase that bridges the clavine and ergoline alkaloid pathways. Chembiochem 7: 645–652.

76. KidwellMG (2002) Genome evolution - Lateral DNA transfer mechanism and consequences. Science 295: 2219–2220.

77. RouxelT, GrandaubertJ, HaneJK, HoedeC, van de WouwAP, et al. (2011) Effector diversification within compartments of the Leptosphaeria maculans genome affected by Repeat-Induced Point mutations. Nat Commun 2: 202.

78. EwaldPW (1987) Transmission modes and evolution of the parasitism-mutualism continuum. Ann N Y Acad Sci 503: 295–306.

79. ZhangD-X, NagabhyruP, SchardlCL (2009) Regulation of a chemical defense against herbivory produced by symbiotic fungi in grass plants. Plant Physiol 150: 1072–1082.

80. MeyG, HeldK, SchefferJ, TenbergeKB, TudzynskiP (2002) CPMK2, an SLT2-homologous mitogen-activated protein (MAP) kinase, is essential for pathogenesis of Claviceps purpurea on rye: evidence for a second conserved pathogenesis-related MAP kinase cascade in phytopathogenic fungi. Molecular Microbiology 46: 305–318.

81. Al-SamarraiTH, SchmidJ (2000) A simple method for extraction of fungal genomic DNA. Lett Appl Microbiol 30: 53–56.

82. CenisJL (1992) Rapid extraction of fungal DNA for PCR amplification. Nucleic Acids Res 20: 2380.

83. AndrieRM, MartinezJP, CiuffettiLM (2005) Development of ToxA and ToxB promoter-driven fluorescent protein expression vectors for use in filamentous ascomycetes. Mycologia 97: 1152–1161.

84. LatchGCM, ChristensenMJ (1985) Artificial infections of grasses with endophytes. Ann Appl Biol 107: 17–24.

85. AnZ-q, SiegelMR, HollinW, TsaiH-F, SchmidtD, et al. (1993) Relationships among non-Acremonium sp. fungal endophytes in five grass species. Appl Environ Microbiol 59: 1540–1548.

86. ChungK-R, SchardlCL (1997) Sexual cycle and horizontal transmission of the grass symbiont, Epichloë typhina. Mycol Res 101: 295–301.

87. PanaccioneDG, CipolettiJR, SedlockAB, BlemingsKP, SchardlCL, et al. (2006) Effects of ergot alkaloids on food preference and satiety in rabbits, as assessed with gene-knockout endophytes in perennial ryegrass (Lolium perenne). J Agric Food Chem 54: 4582–4587.

88. FaulknerJR, HussainiSR, BlankenshipJD, PalS, BrananBM, et al. (2006) On the sequence of bond formation in loline alkaloid biosynthesis. Chembiochem 7: 1078–1088.

89. SpieringMJ, DaviesE, TapperBA, SchmidJ, LaneGA (2002) Simplified extraction of ergovaline and peramine for analysis of tissue distribution in endophyte-infected grass tillers. J Agric Food Chem 50: 5856–5862.

90. RasmussenS, LaneGA, MaceW, ParsonsAJ, FraserK, et al. (2012) The use of genomics and metabolomics methods to quantify fungal endosymbionts and alkaloids in grasses. Methods in Molecular Biology 860: 213–226.

91. FarmanML (2011) Targeted cloning of fungal telomeres. Methods in Molecular Biology 722: 11–31.

92. HuseS, HuberJ, MorrisonH, SoginM, DW (2007) Accuracy and quality of massively parallel DNA pyrosequencing. Genome Biology 8: R143.

93. Smit AFA, Hubley R, Green P (1996–2010) RepeatMasker Open-3.0. 3.0 ed: Institute for Syst Biol.

94. EwingB, HillierL, WendlMC, PG (1998) Base-calling of automated sequencer traces using Phred. I. Accuracy assessment. Genome Res 8: 175–185.

95. MargolinBS, Garrett-EngelePW, StevensJN, FritzDY, Garrett-EngeleC, et al. (1998) A methylated Neurospora 5S rRNA pseudogene contains a transposable element inactivated by repeat-induced point mutation. Genetics 149: 1787–1797.

96. CantarelBL, KorfI, RobbSMC, ParraG, RossE, et al. (2008) MAKER: An easy-to-use annotation pipeline designed for emerging model organism genomes. Genome Res 18: 188–196.

97. JurkaJ, KapitonovVV, PavlicekA, KlonowskiP, KohanyO, et al. (2005) Repbase Update, a database of eukaryotic repetitive elements. Cytogentic and Genome Res 110: 462–467.

98. StankeM, KellerO, GunduzI, HayesA, WaackS, et al. (2006) AUGUSTUS: ab initio prediction of alternative transcripts. Nucleic Acids Res 34: W435–W439.

99. SalamovAA, SolovyevVV (2000) Ab initio gene finding in Drosophila genomic DNA. Genome Res 10: 516–522.

100. EnrightAJ, Van DongenS, OuzounisCA (2002) An efficient algorithm for large-scale detection of protein families. Nucleic Acids Res 30: 1575–1584.

101. SteinLD, MungallC, ShuS, CaudyM, MangoneM, et al. (2002) The generic genome browser: a building block for a model organism system database. Genome Res 12: 1599–1610.

102. Donlin MJ (2007) Chapter 9, Unit 9.9: Using the generic genome browser (GBrowse). Current Protocols in Bioinformatics: Wiley Online Library.

103. Ter-HovhannisyanV, LomsadzeA, ChernoffYO, BorodovskyM (2008) Gene prediction in novel fungal genomes using an ab initio algorithm with unsupervised training. Genome Res 18: 1979–1990.

104. ChenF, MackeyAJ, StoeckertCJ, RoosDS (2006) OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res 34: D363–D368.

105. LiL, StoeckertCJJr, RoosDS (2003) OrthoMCL: identification of ortholog groups for eukaryotic genomes. Genome Res 13: 2178–2189.

106. EdgarRC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797.

107. AltschulSF, MaddenTL, SchäfferAA, ZhangJ, ZhangZ, et al. (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25: 3389–3402.

108. JothiR, ZotenkoE, TasneemA, PrzytyckaTM (2006) COCO-CL: hierarchical clustering of homology relations based on evolutionary correlations. Bioinformatics 22: 779–788.

109. ChennaR, SugawaraH, KoikeT, LopezR, GibsonTJ, et al. (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31: 3497–3500.

110. DereeperA, GuignonV, BlancG, AudicS, BuffetS, et al. (2008) Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res 36: W465–W469.

111. EdgarR (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5: 113.

112. GuindonS, GascuelO (2003) A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52: 696–704.

113. AnisimovaM, GascuelO (2006) Approximate likelihood-ratio test for branches: a fast, accurate, and powerful alternative. Syst Biol 55: 539–552.

114. ShimodairaH, MasamiH (1999) Multiple comparisons of log-likelihoods with applications to phylogenetic inference. Molecular Biology and Evolution 16: 1114–1116.

115. SchliepKP (2011) phangorn: Phylogenetic analysis in R. Bioinformatics 27: 592–593.

116. ZhuYY, MachlederEM, ChenchikA, LiR, SiebertPD (2001) Reverse transcriptase template switching: A SMART (TM) approach for full-length cDNA library construction. Biotechniques 30: 892–897.

117. WangK, SinghD, ZengZ, ColemanSJ, HuangY, et al. (2010) MapSplice: Accurate mapping of RNA-seq reads for splice junction discovery. Nucleic Acids Res 38: e178.

118. YoungCA, TapperBA, MayK, MoonCD, SchardlCL, et al. (2009) Indole-diterpene biosynthetic capability of epichloë endophytes as predicted by ltm gene analysis. Appl Environ Microbiol 75: 2200–2211.

119. LorenzN, OlšovskáJ, ŠulcM, TudzynskiP (2010) Alkaloid cluster gene ccsA of the ergot fungus Claviceps purpurea encodes chanoclavine I synthase, a flavin adenine dinucleotide-containing oxidoreductase mediating the transformation of N-methyl-dimethylallyltryptophan to chanoclavine I. . Appl Environ Microbiol 76: 1822–1830.

120. PanaccioneDG, JohnsonRD, WangJH, YoungCA, DamrongkoolP, et al. (2001) Elimination of ergovaline from a grass-Neotyphodium endophyte symbiosis by genetic modification of the endophyte. Proc Natl Acad Sci U S A 98: 12820–12825.

121. WangJ, MachadoC, PanaccioneDG, TsaiH-F, SchardlCL (2004) The determinant step in ergot alkaloid biosynthesis by an endophyte of perennial ryegrass. Fungal Genet Biol 41: 189–198.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#