Prof. LA Casselton
Research Area
Sexual Development in Fungi
Research Description
The fungi are ideal organisms for studying mechanisms that govern gene expression. I have used the mushroom Coprinus cinereus (Coprinopsis cinerea) as my model for studying the molecular genetics of development and have a special interest in the genes that determine mating compatibility (the mating type genes). Mating leads to major changes in gene expression as two different haploid genomes are brought together in the same cell to initiate a new developmental programme. In the mushroom, two sets of genes are involved, and both encode proteins that are ubiquitous in all eukaryotic organisms. One gene set encodes members of the homeodomain family of DNA-binding proteins and these heterodimerise on mating to generate a new transcription factor. The other gene set encodes small peptide mating pheromones and their 7-transmembrane domain receptors that activate intracellular signalling pathways. Particularly interesting is the fact that the mating type genes are multiallelic, giving C. cinereus more than 12000 “sexes”. The proteins that determine compatibility are highly specific in their interactions, and provide us with novel insights into how similar protein specificity is achieved in higher eukaryotes. The genome sequence of C. cinereus was published in 2003, and more than 11,000 genes are now predicted. I currently work at Warwick HRI and in the USA to optimise the tools to exploit this new resource
Casselton Group Members
Publications (while at this department)
Burns, C, Stajich, J.E, Rechtsteiner, A, Casselton, L, Hanlon, S.E, Wilke, S.K, Savytskyy, O.P, Gathman, A.C, Lilly, W.W, Lieb, J.D, Zolan, M.E, Pukkila, P.J. (2010) Analysis of the basidiomycete Coprinopsis cinerea Reveals conservation of the core meiotic expression Program over half a billion years of evolution PLoS Genetics. 6 (9):.
doi:10.1371/journal.pgen.1001135.
Stajich, J.E, Wilke, S.K, Ahren, D, Au, C.H, Birren, B.W, Borodovsky, M, Burns, C, Canback, B, Casselton, L.A, Cheng, C.K, Deng, J, Dietrich, F.S, Fargo, D.C, Farman, M.L, Gathman, A.C, Goldberg, J, Guigo, R, Hoegger, P.J, Hooker, J.B, Huggins, A, James, T.Y, Kamada, T, Kilaru, S, Kodira, C, Kues, U, Kupfer, D, Kwan, H.S, Lomsadze, A, Li, W, Lilly, W.W, Ma, L.-J, Mackey, A.J, Manning, G, Martin, F, Muraguchi, H, Natvig, D.O, Palmerini, H, Ramesh, M.A, Rehmeyer, C.J, Roe, B.A, Shenoy, N, Stanke, M, Ter-Hovhannisyan, V, Tunlid, A, Velagapudi, R, Vision, T.J, Zeng, Q, Zolan, M.E, Pukkila, P.J. (2010) Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus) Proceedings of the National Academy of Sciences of the United States of America. 107 (26): pp 11889-11894.
doi:10.1073/pnas.1003391107.
Casselton, L.A. (2008) Fungal sex genes - Searching for the ancestors BioEssays. 30 (8): pp 711-714.
doi:10.1002/bies.20782.
Riquelme, M, Challen, M.P, Casselton, L.A, Brown, A.J. (2005) The origin of multiple B mating specificities in Coprinus cinereus Genetics. 170 (3): pp 1105-1119.
doi:10.1534/genetics.105.040774.
Casselton, L, Zolan, M. (2002) The art and design of genetic screens: Filamentous fungi Nature Reviews Genetics. 3 (9): pp 683-697.
doi:10.1038/nrg889.
Brown, A.J, Casselton, L.A. (2001) Mating in mushrooms: Increasing the chances but prolonging the affair Trends in Genetics. 17 (7): pp 393-400.
doi:10.1016/S0168-9525(01)02343-5.
Halsall, J.R, Milner, M.J, Casselton, L.A. (2000) Three subfamilies of pheromone and receptor genes generate multiple b mating specificities in the mushroom Coprinus cinereus Genetics. 154 (3): pp 1115-1123
Olesnicky, N.S, Brown, A.J, Honda, Y, Dyos, S.L, Dowell, S.J, Casselton, L.A. (2000) Self-compatible B mutants in Coprinus with altered pheromone-receptor specificities Genetics. 156 (3): pp 1025-1033
Olesnicky, N.S, Brown, A.J, Dowell, S.J, Casselton, L.A. (1999) A constitutively active G-protein-coupled receptor causes mating self-compatibility in the mushroom Coprinus EMBO Journal. 18 (10): pp 2756-2763.
doi:10.1093/emboj/18.10.2756.
Casselton, L.A, Olesnicky, N.S. (1998) Molecular genetics of mating recognition in basidiomycete fungi Microbiology and Molecular Biology Reviews. 62 (1): pp 55-70
O'Shea, S.F, Chaure, P.T, Halsall, J.R, Olesnicky, N.S, Leibbrandt, A, Connerton, I.F, Casselton, L.A. (1998) A large pheromone and receptor gene complex determines multiple B mating type specificities in Coprinus cinereus Genetics. 148 (3): pp 1081-1090
Spit, A, Hyland, R.H, Mellor, E.J.C, Casselton, L.A. (1998) A role for heterodimerization in nuclear localization of a homeodomain protein Proceedings of the National Academy of Sciences of the United States of America. 95 (11): pp 6228-6233.
doi:10.1073/pnas.95.11.6228.
Asgeirsdottir, S.A, Halsall, J.R, Casselton, L.A. (1997) Expression of two closely linked hydrophobin genes of Coprinus cinereus is monokaryon-specific and down-regulated by the oid-1 mutation Fungal Genetics and Biology. 22 (1): pp 54-63.
doi:10.1006/fgbi.1997.0992.
Chaure, P.T, Casselton, L.A, Connerton, I.F. (1997) Molecular analysis of the isocitrate lyase gene (acu-7) of the mushroom Coprinus cinereus Gene. 184 (2): pp 185-187.
doi:10.1016/S0378-1119(96)00593-8.
Asante-Owusu, R.N, Banham, A.H, Bohnert, H.U, Mellor, E.J.C, Casselton, L.A. (1996) Heterodimerization between two classes of homeodomain proteins in the mushroom Coprinus cinereus brings together potential DNA-binding and activation domains Gene. 172 (1): pp 25-31.
doi:10.1016/0378-1119(96)00177-1.
Pardo, E.H, O'Shea, S.F, Casselton, L.A. (1996) Multiple versions of the A mating type locus of Coprinus cinereus are generated by three paralogous pairs of multiallelic homeobox genes Genetics. 144 (1): pp 87-94
Banham, A.H, Asante-Owusu, R.N, Gottgens, B, Thompson, S.A, Kingsnorth, C.S, Mellor, E.J, Casselton, L.A. (1995) An N-terminal dimerization domain permits homeodomain proteins to choose compatible partners and initiate sexual development in the mushroom Coprinus cinereus Plant Cell. 7 (6): pp 773-783.
doi:10.1105/tpc.7.6.773.
Kues, U, Tymon, M, Richardson, W.V.J, May, G, Gieser, P.T, Casselton, L.A. (1994) A mating-type factors of Coprinus cinereus have variable numbers of specificity genes encoding two classes of homeodomain proteins Molecular and General Genetics. 245 (1): pp 45-52.
doi:10.1007/BF00279749.
Kues, U, Gottgens, B, Stratmann, R, Richardson, W.V.J, O'Shea, S.F, Casselton, L.A. (1994) A chimeric homeodomain protein causes self-compatibility and constitutive sexual development in the mushroom Coprinus cinereus EMBO Journal. 13 (17): pp 4054-4059
Kues, U, Asante-Owusu, R.N, Mutasa, E.S, Tymon, A.M, Pardo, E.H, O'Shea, S.F, Gottgens, B, Casselton, L.A. (1994) Two classes of homeodomain proteins specify the multiple A mating types of the mushroom Coprinus cinereus Plant Cell. 6 (10): pp 1467-1475.
doi:10.1105/tpc.6.10.1467.
Challen, M.P, Elliott, T.J, Kues, U, Casselton, L.A. (1993) Expression of A mating type genes of Coprinus cinereus in a heterologous basidiomycete host Molecular and General Genetics. 241: pp 474-478
Kues, U, Casselton, L.A. (1993) The origin of multiple mating types in mushrooms Journal of Cell Science. 104 (2): pp 227-230
Richardson, W.V.J, Kues, U, Casselton, L.A. (1993) The A mating-type genes of the mushroom Coprinus cinereus are not diferentially transcribed in monikaryons and dikaryons Molecular and General Genetics. 238: pp 304-307
Kues, U, Casselton, L.A. (1992) Homeodomains and regulation of sexual development in basidiomycetes Trends in Genetics. 8 (5): pp 154-155
Kues, U, Casselton, L.A. (1992) Molecular and functional analysis of the A mating type genes of Coprinus cinereus. Genetic engineering. 14: pp 251-268
Kues, U, Richardson, W.V.J, Tymon, A.M, Mutasa, E.S, Gottgens, B, Gaubatz, S, Gregoriades, A, Casselton, L.A. (1992) The combination of dissimilar alleles of the Aα and Aβ gene complexes, whose proteins contain homeo domain motifs, determines sexual development in the mushroom Coprinus cinereus Genes and Development. 6 (4): pp 568-577
Maconochie, M.K, Connerton, I.F, Casselton, L.A. (1992) The acu-1 gene of Coprinus cinereus is a regulatory gene required for induction of acetate utilisation enzymes Molecular and General Genetics. 234 (2): pp 211-216
Collaborators
Dr Mike Challen, Warwick HRI, Wellesbourne, UK
Professor Patricia Pukkila, University of N. Carolina, Chapel Hill
Professor Miriam Zolan, University of Indiana, Bloomington, U
Professor Takashi Kamada, University of Okayama, Japan