Box 3568 DUMC
Durham, N.C. 27710
Phone: (919) 684-2857
Fax: (919) 684-2790
fred.dietrich@duke.edu
Research
In our laboratory we are interested in using genomic technology to address several fundamental biological questions.
What is the set of genes found in the fungi?
The starting point for this work is the complete sequence of the genome of the yeast Saccharomyces cerevisiae. When the sequence of this genome became available at the end of 1996 it became clear that the genome of this yeast encodes about 6000 genes. While many groups are studying this particular research strain to learn more about basic fungal biology we are taking a somewhat different approach. By characterizing the genomes of related organisms starting with the filamentous fungus Ashbya gossypii we hope to more precisely define what are the set of genes in S. cerevisiae as well as to identify genes found in related fungi that have been lost from the genome of this yeast. Considerably more than 90% of the genes found in S. cerevisiae are found in Ashbya gossypii and likewise well over 90% of the genes found in Ashbya gossypiiarefound in S. cerevisiae. This suggests that the set of genes found in this family of fungi is somewhat larger than the set of genes found in the standard research yeast, but not by very much.
How much genetic variation is there within a fungal pathogen species?
Our interest in this human pathogen is to expand beyond looking at one isolate and to investigate the diversity in the population. Are there genes found in some Cryptococcus neoformans isolates but not in others? Are there regions of the genome or individual genes which are highly diverged between Cryptococcus isolates? Efforts are now underway at Stanford University to sequence the genome of the JEC21 strain of Cryptococcus. This is a strain that has been agreed upon by the community of Cryptococcus researchers as a reference strain. But how much do other Cryptococcus isolates differ from JEC21?
What is the set of genes in humans?
The complete DNA sequence of human and mouse will become available soon. This does not mean that we will know the complete set of human or mouse genes. Our current state of knowledge does not allow us to accurately predict human genes directly from DNA sequence. We are interested in applying to the human genome some of the experimental and bioinformatic tools we are developing and utilizing in fungal systems.
We are currently establishing a high throughput sequencing and bioinformatics capacity to address the above questions.
Biography
Fred Dietrich was an undergraduate math major at the University of California, Davis, and then a graduate student at the Massachusetts Institute of Technology (MIT) in Gerry Fink’s lab. He moved to Stanford to join the S. cerevisiae genome project, working with Ron Davis and David Botstein to complete yeast chromosome V.
Fred moved to the Biozentrum, University of Basel in Switzerland in 1997 and spent three years as a post-doctoral fellow with Peter Phillipsen sequencing the genome of the filamentous ascomycete Ashbya gossypii. He was recruited to the Department of Molecular Genetics and Microbiology (MGM) at Duke in July 2000 where his attention focuses on the genomic evolution of fungi, most importantly, the pathogenic basidiomycete Cryptococcus neoformans serotype A. He is also interested in the interface between automated sequence acquisition and bioinformatics and in how to visualize genomic information.
Publications
Representative Publications:
Vijayraghavan S, Kozmin SG, Strope PK, Skelly DA, Lin Z, Kennell J, Magwene PM, Dietrich FS, McCusker JH. Mitochondrial Genome Variation Affects Multiple Respiration and Non-respiration Phenotypes in Saccharomyces cerevisiae. Genetics. 2018 Nov 29. pii: genetics.301546.2018. doi: 10.1534/genetics.118.301546. [Epub ahead of print]
Strope PK, Skelly DA, Kozmin SG, Mahadevan G, Stone EA, Magwene PM, Dietrich FS, McCusker JH. (2015). The 100-genomes strains, an S. cerevisiae resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen. Genome Res. 2015 May;25(5):762-74. doi: 10.1101/gr.185538.114. Epub 2015 Apr 3.
Zhao Y, Strope PK, Kozmin SG, McCusker JH, Dietrich FS, Kokoska RJ, Petes TD (2014). Structures of naturally-evolved CUP1 Tandem arrays in yeast indicate that these arrays are generated by unequal non-homologous recombination. G3. 2014 Sep 17 4:2259-69.
Dietrich FS, Voegeli S, Kuo S, Philippsen P. (2013). Genomes of Ashbya fungi isolated from insects reveal four mating-type loci, numerous translocations, lack of transposons, and distince gene duplications. G3 (Bethesda), 2013 Jun 7 3:1225-39.
McDonald TR, Mueller O, Dietrich FS, Lutzoni F. (2013). High-throughput genome sequencing of lichenizing fungi to assess gene loss in the ammonium transporter/ammonia permease gene family. BMC Genomics, 2013 Apr 4. 4:225.
Cirulli ET, Heinzen EL, Dietrich FS, Shianna KV, Singh A, Maia JM, Goedert JJ, Goldstein DB. (2011). A whole-genome analysis of premature termination codons. Genomics, 2011 Nov 98:337-42.
McDonald T, Dietrich FS, Lutzoni F. (2011). Multiple horizontal gene transfers of ammonium transporters/ammonia permeases from prokaryotes to eukaryotes: Toward a new functional and evolutionary classification. Mol Biol Evol., 2012 Jan 29:51-60.
Diezmann S, Dietrich FS. Oxidative stress survival in a clinical Saccharomyces cerevisiae isolate is influenced by a major quantitative trait nucleotide. Genetics.,188(3):709-722. [Epub 2011 Apr 21].
Stajich JE, Wilke SK, Ahrén D, Au CH, Birren BW, Borodovsky M, Burns C, Canbäck B, Casselton LA, Cheng CK, Deng J, Dietrich FS, Fargo DC, Farman ML, Gathman AC, Goldberg J, Guigó R, Hoegger PJ, Hooker JB, Huggins A, James TY, Kamada T, Kilaru S, Kodira C, Kües U, Kupfer D, Kwan HS, Lomsadze A, Li W, Lilly WW, Ma LJ, Mackey AJ, Manning G, Martin F, Muraguchi H, Natvig DO, Palmerini H, Ramesh MA, Rehmeyer CJ, Roe BA, Shenoy N, Stanke M, Ter-Hovhannisyan V, Tunlid A, Velagapudi R, Vision TJ, Zeng Q, Zolan ME, Pukkila PJ. (2010). Insights into evolution of multicellular fungi from the assembled chromosomes of the mushroom Coprinopsis cinerea (Coprinus cinereus). Proc Natl Acad Sci USA, 107(26):11889-11894.
Lee SC, Corradi N, Doan S, Dietrich FS, Keeling PJ, Heitman J. (2010). Evolution of the sex-related locus and genomic features shared in microsporidia and fungi. PLoS One, 5(5):e10539.
Rodriguez-Carres M, Findley K, Sun S, Dietrich FS, Heitman J. (2010). Morphological and genomic characterization of Filobasidiella depauperata: A homothallic sibling species of the pathogenic Cryptococcus species complex. PLoS One, 5(3):e9620.
Argueso JL, Carazzolle MF, Mieczkowski PA, Duarte FM, Netto OV, Missawa SK, Galzerani F, Costa GG, Vidal RO, Noronha MF, Dominska M, Andrietta MG, Andrietta SR, Cunha AF, Gomes LH, Tavares FC, Alcarde AR, Dietrich FS, McCusker JH, Petes TD, Pereira GA. (2009). Genome structure of a Saccharomyces cerevisiae strain widely used in bioethanol production. Genome Res, 19(12):2258-2270. [Epub 2009 Oct 7].
Diezmann S, Dietrich FS. (2009). Saccharomyces cerevisiae: Population divergence and resistance to oxidative stress in clinical, domesticated and wild isolates. PLoS One, 4(4):e5317.
Kavanaugh LA and Dietrich FS. (2009). Non-coding RNA prediction and verification in Saccharomyces cerevisiae. PLoS Genet, 5(1):e1000321.
Lee SC, Corradi N, Byrnes EJ, III, Torres-Martinez S, Dietrich FS, Keeling PJ, Heitman, J. (2008). Microsporidia evolved from ancestral sexual fungi. Curr Biol, Oct 29.
Hu G, Liu I, Sham A, Stajich JE, Dietrich FS, Kronstad JW. (2008). Comparative hybridization reveals extensive genome variation in the AIDS-associated pathogen Cryptococcus neoformans. Genome Biol, 9(2):R41.
Luedi PP, Dietrich FS, Weidman JR, Bosko JM, Jirtle RL, Hartemink AJ. (2007). Computational and experimental identification of novel human imprinted genes. Genome Res, 17:1723-1730.
Stajich JE, Dietrich FS, Roy SW. (2007). Comparative genomic analysis of fungal genomes reveals intron-rich ancestors. Genome Biol, 8(10):R223.
Wei W, McCusker JH, Hyman RW, Jones T, Ning Y, Cao Z, Gu Z, Bruno D, Miranda M, Nguyen M, Wilhelmy J, Komp C, Tamse R, Wang X, Jia P, Luedi P, Oefner PJ, David L, Dietrich FS, Li Y, Davis RW, Steinmetz LM. (2007). Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. Proc Natl Acad Sci USA, 104(31):12825-12830.
Harrison LB, Yu Z, Stajich JE, Dietrich FS, Harrison PM. (2007). Evolution of budding yeast prion-determinant sequences across diverse fungi. J Mol Biol, 368(1):273-282.
Gattiker A, Rischatsch R, Demougin P, Voegeli S, Dietrich FS, Philippsen P, Primig M. (2007). Ashbya Genome Database 3.0: A cross-species genome and transcriptome browser for yeast biologists. BMC Genomics, 8:9.
Hall C, Dietrich FS. (2007). The reacquisition of biotin prototrophy in Saccharomyces cerevisiae involved horizontal gene transfer, gene duplication and gene clustering. Genetics, 177(4):2293-2307.
Giles SS, Stajich JE, Nichols C, Gerrald QD, Alspaugh JA, Dietrich FS, Perfect JR. (2006). The Cryptococcus neoformans catalase gene family and its role in antioxidant defense. Eukaryot Cell, 5(9):1447-59.
Cramer RA Jr, Stajich JS, Yamanaka Y, Dietrich FS, Steinbach WJ, Perfect JR. (2006). Phylogenomic analysis of non-ribosomal peptide synthetases in the genus Aspergillus. Gene, 383:24-32.
Kavanaugh LA, Fraser JA, Dietrich FS. (2006). Evolution of the human pathogen Cryptococcus neoformans by intervarietal transfer of a 14-gene fragment. Mol Biol Evol, 23(10):1879-90.
Fraser JA, Lim SM, Diezmann S, Wenink EC, Arndt CG, Cox GM, Dietrich FS, Heitman J. (2006). Yeast diversity sampling on the San Juan Islands reveals no evidence for the spread of the Vancouver Island Cryptococcus gattii outbreak to this locale. FEMS Yeast Res, 6(4):620-4.
Stajich JE, Dietrich FS. (2006). Evidence of mRNA-mediated intron loss in the human-pathogenic fungus Cryptococcus neoformans. Eukaryot Cell, 5(5):789-93.
Allen A, Stajich JE, Dietrich FS, Perfect JR, Heitman J. (2005). Same-sex mating and the origin of the Vancouver Island Cryptococcus gattii outbreak. Nature, 437(7063):1360-4.
Zhang Z and Dietrich FS. (2005). Identification and characterization of upstream open reading frames (uORF) in the 5′ untranslated regions (UTR) of genes in Saccharomyces cerevisiae. Current Genetics, 13:1-11. [Epub ahead of print].
Hall C, Brachat S, and Dietrich FS. (2005). Contribution of horizontal gene transfer to the evolution of Saccharomyces cerevisiae. Eukaryotic Cell, 4:1102-1115.
Zhang Z and Dietrich FS. (2005). Mapping of transcription start sites in Saccharomyces cerevisiae using 5′ SAGE. Nucleic Acids Res, 33:2838-2851.
Campbell LT, Fraser JA, Nichols CB, Dietrich FS, Carter D, and Heitman J. (2005). Clinical and environmental isolates of Cryptococcus gattii from Australia that retain sexual fecundity. Eukaryotic Cell, 4:1410-1419.
Fraser JA, Diezmann S, Subaran RL, Allen A, Lengeler KB, Dietrich FS, Heitman J. (2004). Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms. PLoS Biology, 12:0001-0013.
Kraus PR, Boily M-J, Giles SS, Stajich JE, Allen A. Cox GM, Dietrich FS, Perfect JR, Heitman J. (2004). Identification of Cryptococcus neoformans temperature-regulated genes with a genomic-DNA microarray. Eukaryotic Cell, 3(5):1249-1260.
Dietrich FS, Voegeli S, Brachat S, Lerch A, Gates K, Steiner S, Mohr C, Pohlmann R, Luedi P, Choi S, Wing RA, Flavier A, Gaffney TD, Philippsen P. (2004). The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science, 304(5668)304-307.
Toffaletti DL, Nielsen K, Dietrich FS, Heitman J, and Perfect JR. (2004). Cryptococcus neoformans mitochondiral genomes from serotype A and D strains do not influence viurlence. Current Genetics, 46:193-204.
Brachat S, Dietrich FS, Voegeli S, Zhang Z, Stuart L, Lerch A. (2003). Reinvestigation of the Saccharomyces cerevisiae genome annotation by comparison to the genome of a related fungus: Ashbya gossypii. Genome Biology, 4:R45.
Zhang Z, Dietrich FS. (2003). Verification of a new gene on Saccharomyces cerevisiae chromosome III. Yeast, 20(8):731-738.
Toffaletti DL, Dei Poeta M, Rude TH, Dietrich FS, Perfect JR. (2003). Regulation of cytochrome c oxidase subunit 1 (COX 1) expression in Cryptococcus by temperature and host environment. Microbiology, 149(Pt4):1041-1049.
Jarvis ED, Smith VA, Wada K, Rivas MV, McElroy M, Smulders TV, Carninici P, Hayashizaki Y, Dietrich FS, Wu X, McConnell P, Yu J, Want PP, Haremink AF, Lin S. (2002) A framework for integrating the songbird brain. J. Comp Physiol A Neuroethol Sens Neural Behav Physiol, 188(11-12):961-980.
Lengeler KB, Fox DS, Fraser JA, Allen A, Forrester K, Dietrich FS, Heitman J. (2002) The mating type locus of Cryptococcus neoforms: a step in the evolution of sex chromosomes. Eukaryotic Cell, 1:704-718.
Alberti-Sequi C, Dietrich FS, Altmann-Johl R, Heopfner D, Phippsen P. (2001). Cytoplasmic dynein is required to oppose the force that moves nuclei towards the hyphal tip in the filamentous ascomycete Ashbya gossypii. J. Cell. Science, 114:975-986.
Ayad-Durieux Y, Knechtle P, Dietrich FS, Philippsen P. (2000). A PAK-like protein kinase is required for maturation of young hyphae and septation in the filamentous ascomycete Ashbya gossypii. J Cell Science, 113:4563-4575.
Wendland J, Pohlmann R, Dietrich FS, Steiner S, Moh, C, Philippsen P. (1999). Compact organization of rRNA genes in the filamentous fungus Ashbya gossypii. Current Genetics, 35:618-625.
Winzeler EA, Shoemaker DD, Astromoff A, Liang H, Anderson K, Andre B, Bangham R, Benito R, Boeke JD, Bussey H, Chu AM, Connelly C, Davis K, Dietrich FS, Dow SW, El Bakkoury M, Foury F, Friend SH, Gentalen E, Giaever G, Hegemann JH, Jones T, Laub M, Liao H, Liebundguth N, Lockhart DJ, Lucau-Danila A, Lussier M, M’Rabet N, Menard P, Mittmann M, Pai C, Rebischung C, Revuelta JL, Riles L, Roberts CJ, Ross-MacDonald P, Scherens B, Snyder M, Sookhai-Mahadeo S, Storms RK, Vronneau S, Voet M, Volckaert G, Ward TR, Wysocki R, Yen GS, Yu K, Zimmermann K, Philippsen P, Johnston M, Davis RW. (1999). Functional Characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science, 5429: 901-906.
Dietrich FS, Mulligan J, Hennessy K, Yelton MA, et al. (1997). The nucleotide sequence of Saccharomyces cerevisiae chromosome V. Nature, 387:(6632 suppl) 78-81.
Bussey, H., et al. (1997). The nucleotide sequence of Sacchromyces cerevisiae chromosome XVI. Nature, 387 (6632 suppl):103-105.
Oefner PJ, Hunicke-Smith SP, Chiang L, Dietrich FS, Mulligan J, Davis RW. (1996). Efficient random subcloning of DNA sheared in a recirculating point-sink flow system. Nucleic Acids Res, 24:3879-3886.