title: Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus.
abstract: The fungal genus Aspergillus is of critical importance to humankind. Species include those with industrial applications, important pathogens of humans, animals and crops, a source of potent carcinogenic contaminants of food, and an important genetic model. The genome sequences of eight aspergilli have already been explored to investigate aspects of fungal biology, raising questions about evolution and specialization within this genus.
  
  
  
  We have generated genome sequences for ten novel, highly diverse Aspergillus species and compared these in detail to sister and more distant genera. Comparative studies of key aspects of fungal biology, including primary and secondary metabolism, stress response, biomass degradation, and signal transduction, revealed both conservation and diversity among the species. Observed genomic differences were validated with experimental studies. This revealed several highlights, such as the potential for sex in asexual species, organic acid production genes being a key feature of black aspergilli, alternative approaches for degrading plant biomass, and indications for the genetic basis of stress response. A genome-wide phylogenetic analysis demonstrated in detail the relationship of the newly genome sequenced species with other aspergilli.
  
  
  
  Many aspects of biological differences between fungal species cannot be explained by current knowledge obtained from genome sequences. The comparative genomics and experimental study, presented here, allows for the first time a genus-wide view of the biological diversity of the aspergilli and in many, but not all, cases linked genome differences to phenotype. Insights gained could be exploited for biotechnological and medical applications of fungi.
authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands. r.devries@cbs.knaw.nl.|Fungal Molecular Physiology, Utrecht University, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands. r.devries@cbs.knaw.nl.
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Fungal Molecular Physiology, Utrecht University, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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authors.affiliation: Institute of Biology Leiden, Molecular Microbiology and Biotechnology, Leiden University, Sylviusweg 72, 2333, BE, Leiden, The Netherlands.|Present address: CSIRO Publishing, Unipark, Building 1 Level 1, 195 Wellington Road, Clayton, VIC, 3168, Australia.
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authors.affiliation: US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
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authors.affiliation: Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Georg August University Göttingen, Grisebachstr. 8, 37077, Göttingen, Germany.|Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Fungal Molecular Physiology, Utrecht University, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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authors.affiliation: US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.|Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, CEP 13083-862, Campinas, SP, Brazil.
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authors.forename: Iran
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authors.affiliation: Uppsala BioCenter, Department of Microbiology, Swedish University of Agricultural Sciences, P.O. Box 7025, 750 07, Uppsala, Sweden.|Present address: Swedish Chemicals Agency, Box 2, 172 13, Sundbyberg, Sweden.
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authors.forename: Natalia
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authors.affiliation: Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, 4032, Debrecen, Hungary.|MTA-DE Momentum, Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Nagyerdei krt.98., 4032, Debrecen, Hungary.
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, 4032, Debrecen, Hungary.
authors.forename: Erzsébet
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authors.affiliation: Institute of Biology Leiden, Molecular Microbiology and Biotechnology, Leiden University, Sylviusweg 72, 2333, BE, Leiden, The Netherlands.|Present address: Centre for Structural and Functional Genomics, Concordia University, 7141 Sherbrooke Street West, Montreal, QC, H4B 1R6, Canada.
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.
authors.forename: Diego Mauricio
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.
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authors.affiliation: US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
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authors.affiliation: School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.|Department of Biology, School of Science, University of Sulaimani, Al Sulaymaneyah, Iraq.
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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authors.affiliation: Institute of Biology Leiden, Molecular Microbiology and Biotechnology, Leiden University, Sylviusweg 72, 2333, BE, Leiden, The Netherlands.|Present address: Department Applied and Molecular Microbiology, Institute of Biotechnology, Berlin University of Technology, Gustav-Meyer-Allee 25, 13355, Berlin, Germany.
authors.forename: Tabea
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authors.affiliation: Systems Biology/Bioinformatics group, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, (HKI), Beutenbergstr. 11a, 07745, Jena, Germany.
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.
authors.forename: Fabio M
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authors.affiliation: US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
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authors.affiliation: Institute of Sciences of Food Production (ISPA), National Research Council (CNR), Via Amendola 122/O, 70126, Bari, Italy.
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authors.affiliation: Department of Plant Pathology, Kansas State University, Manhattan, KS, 66506, USA.
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authors.initials: RB
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authors.affiliation: Centre for Structural and Functional Genomics, Concordia University, 7141 Sherbrooke Street West, Montreal, QC, H4B 1R6, Canada.
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authors.affiliation: School of Biology, University of St Andrews, St Andrews, Fife, KY16 9TH, UK.
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authors.initials: SE
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Nathalie
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authors.affiliation: Institute of Biology Leiden, Molecular Microbiology and Biotechnology, Leiden University, Sylviusweg 72, 2333, BE, Leiden, The Netherlands.|Present address: BaseClear B.V., Einsteinweg 5, 2333, CC, Leiden, The Netherlands.
authors.forename: Diana
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authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, CEP 13083-970, Campinas, São Paulo, Brasil.
authors.forename: Juliana Velasco de Castro
authors.initials: JV
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authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800, Kongens Lyngby, Denmark.
authors.forename: Tammi C
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
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authors.affiliation: Departments of Bacteriology and Genetics, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, USA.
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authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Fungal Molecular Physiology, Utrecht University, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Miaomiao
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authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800, Kongens Lyngby, Denmark.
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authors.affiliation: School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
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authors.lastname: Archer
authors.affiliation: Fungal Biotechnology Team, Pacific Northwest National Laboratory, Richland, Washington, 99352, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Baker
authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Fungal Molecular Physiology, Utrecht University, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Present address: Centre of Functional and Structure Genomics Biology Department Concordia University, 7141 Sherbrooke St. W., Montreal, QC, H4B 1R6, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Benoit
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology - Hans Knoell Institute (HKI) and Institute for Microbiology, Friedrich Schiller University Jena, Beutenbergstr. 11a, 07745, Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.affiliation: Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Georg August University Göttingen, Grisebachstr. 8, 37077, Göttingen, Germany.
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
authors.affiliation: Department of Microbiology, Karlsruhe Institute of Technology, Institute for Applied Biosciences, Hertzstrasse 16,, 76187, Karlsruhe, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 223, 2800, Kongens Lyngby, Denmark.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Frisvad
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café S/N, CEP 14040-903, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Houbraken
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, 66045, USA.
authors.forename: Berl
authors.initials: B
authors.lastname: Oakley
authors.affiliation: Department of Biotechnology and Microbiology, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, 4032, Debrecen, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Pócsi
authors.affiliation: Department of Microbiology, Imperial College, London, SW7 2AZ, UK.|Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Claudio
authors.initials: C
authors.lastname: Scazzocchio
authors.affiliation: Research Division Biochemical Technology, Institute of Chemical Engineering, TU Wien, Gumpendorferstraße 1a, 1060, Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Seiboth
authors.affiliation: Westerdijk Fungal Biodiversity Institute, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.|Institute of Biology Leiden, Molecular Microbiology and Biotechnology, Leiden University, Sylviusweg 72, 2333, BE, Leiden, The Netherlands.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: vanKuyk
authors.affiliation: Broad Institute, 415 Main St, Cambridge, MA, 02142, USA.|Present address: Seres Therapeutics, 200 Sidney St, Cambridge, MA, 02139, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wortman
authors.affiliation: School of Life Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Dyer
authors.affiliation: US Department of Energy Joint Genome Institute, 2800 Mitchell Drive, Walnut Creek, CA, 94598, USA.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Grigoriev
mesh_terms: D000220:Adaptation, Biological; D001230:Aspergillus / Q000145:classification* / Q000235:genetics* / Q000378:metabolism; D044822:Biodiversity; D018533:Biomass; D002244:Carbon / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods; D006801:Humans; D053858:Metabolic Networks and Pathways; D058977:Molecular Sequence Annotation; D005810:Multigene Family; D010088:Oxidoreductases / Q000378:metabolism; D010802:Phylogeny; D010944:Plants / Q000378:metabolism / Q000382:microbiology; D064210:Secondary Metabolism / Q000235:genetics; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics
chemical_list: D005656:Fungal Proteins; D002244:Carbon; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases
keywords: Aspergillus; Comparative genomics; Fungal biology; Genome sequencing