Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid loci

Authors: SCHARDL, CHRISTOPHER - University Of Kentucky; YOUNG, CAROLYN - Samuel Roberts Noble Foundation, Inc; HESSE, ULJANA - University Of The Western Cape; AMYOTTE, STEFAN - University Of Ottawa; ANDREEVA, KALINA - University Of California; CALIE, PATRICK - Eastern Kentucky University; FLEETWOOD, DAMIEN - Agresearch; HAWS, DAVID - University Of Kentucky; MOORE, NEIL - University Of Kentucky; OESER, BIRGITT - University Of Munster; PANACCIONE, DANIEL - West Virginia University; SCHWERI, KATHRYN - North Carolina State University; VOISEY, CHRISTINE - Agresearch; FARMAN, MARK - University Of Kentucky; JAROMCZYK, JERZY - University Of Kentucky; ROE, BRUCE - University Of Oklahoma; O'SULLIVAN, DONAL - National Institute Of Agricultural Botany (NIAB); SCOTT, BARRY - Massey University; TUDZYNSKI, PAUL - University Of Munster; AN, ZHIQIANG - University Of Texas Health Science Center; ARNAOUDOVA, ELISSAVETA - University Of Kentucky; BULLOCK, CHARLES - University Of Kentucky; CHARLTON, NIKKI - Samuel Roberts Noble Foundation, Inc; CHEN, LI - University Of Kentucky; COX, MURRAY - Massey University; Dinkins, Randy; FLOREA, SIMONA - University Of Kentucky; Glenn, Anthony - Tony; GORDON, ANNA - National Institute Of Agricultural Botany (NIAB); GULDENER, ULRICH - Institute For Bioinformatics - Germany; HARRIS, DANIEL - University Of Kentucky; HOLLIN, WALTER - University Of Kentucky; JAROMCZYK, JOLANTA - University Of Kentucky; JOHNSON, RICHARD - Agresearch; KHAN, ANAR - Agresearch; LEISTNER, ECKHARD; LEUCHTMANN, ADRIAN - Eth Zurich; LI, CHUNJIE - Lanzhou University; LIU, JINGE - University Of Kentucky; LIU, JINZE - University Of Kentucky; LIU, MIAO - University Of Kentucky; MACE, WADE - Agresearch; MACHADO, CAROLINE - Indiana University; NAGABHYRU, PADMAJA - University Of Kentucky; PAN, JUAN - University Of Kentucky; SCHMID, JAN - Massey University; SUGAWARA, KOYA - National Agricultural Research Organization - Japan (NARO); STEINER, ULRIKE; TAKACH, JOHANNA - Samuel Roberts Noble Foundation, Inc; TANAKA, EIJI - Ishikawa Prefectural University; WEBB, JENNIFER - University Of Kentucky; WILSON, ELLA - University Of North Carolina; WISEMAN, JENNIFER - Life Technologies Corporation; YOSHIDA, RURIKO - University Of Kentucky; ZENG, SHENG - University Of Kentucky

Submitted to: PLoS Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/31/2012
Publication Date: 2/28/2013
Citation: Schardl, C.L., Young, C.A., Hesse, U., Amyotte, S.G., Andreeva, K., Calie, P.J., Fleetwood, D.J., Haws, D.C., Moore, N., Oeser, B., Panaccione, D.G., Schweri, K.K., Voisey, C.R., Farman, M.L., Jaromczyk, J.W., Roe, B.A., O'Sullivan, D.M., Scott, B., Tudzynski, P., An, Z., Arnaoudova, E., Bullock, C.T., Charlton, N.D., Chen, L., Cox, M., Dinkins, R.D., Florea, S., Glenn, A.E., Gordon, A., Guldener, U., Harris, D.R., Hollin, W., Jaromczyk, J., Johnson, R.D., Khan, A.K., Leistner, E., Leuchtmann, A., Li, C., Liu, J., Liu, J., Liu, M., Mace, W., Machado, C., Nagabhyru, P., Pan, J., Schmid, J., Sugawara, K., Steiner, U., Takach, J.E., Tanaka, E., Webb, J.S., Wilson, E., Wiseman, J., Yoshida, R., Zeng, S. 2013. Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid loci. PLoS Genetics. 9(2):e1003323. doi:10.1371/journal.pgen.1003323.

Interpretive Summary: The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several potent psychoactive and bioprotective alkaloids. The family includes grass-symbiotic epichloae (Epichloë and Neotyphodium species), which have highly diverse chemotypes with four distinct classes of anti-insect and anti-mammalian alkaloids. Epichloae also vary widely in host-interactions, some being pathogenic and contagious, and others being mutualistic and vertically transmitted (seed-borne). We sequenced genomes of seven epichloae, two related symbionts, and three ergot fungi, and compared their alkaloid gene clusters. The clusters tend to have conserved cores that specify the alkaloid skeleton structures, and peripheral genes for variations affecting pharmacological specificities. In contrast to most secondary metabolite gene clusters, the alkaloid loci have large retroelement-derived repeat-arrays, especially in the epichloae. Such repeats can facilitate gene rearrangements, deletions, duplications and neofunctionalization, suggesting that epichloae are under selection for alkaloid diversification, perhaps due to their highly variable life histories and plant-protective roles.

Technical Abstract: The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several potent psychoactive and bioprotective alkaloids. The family includes grass-symbiotic epichloae (Epichloë and Neotyphodium species), which have highly diverse chemotypes with four distinct classes of anti-insect and anti-mammalian alkaloids. Epichloae also vary widely in host-interactions, some being pathogenic and contagious, and others being mutualistic and vertically transmitted (seed-borne). We sequenced genomes of seven epichloae, two related symbionts, and three ergot fungi, and compared their alkaloid gene clusters. The clusters tend to have conserved cores that specify the alkaloid skeleton structures, and peripheral genes for variations affecting pharmacological specificities. In contrast to most secondary metabolite gene clusters, the alkaloid loci have large retroelement-derived repeat-arrays, especially in the epichloae. Such repeats can facilitate gene rearrangements, deletions, duplications and neofunctionalization, suggesting that epichloae are under selection for alkaloid diversification, perhaps due to their highly variable life histories and protective roles.