© 2005 Nature Publishing Group Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus William C. Nierman 1 , Arnab Pain 2 , Michael J. Anderson 3 , Jennifer R. Wortman 1 , H. Stanley Kim 1 , Javier Arroyo 4 , Matthew Berriman 2 , Keietsu Abe 5 , David B. Archer 6 , Clara Bermejo 4 , Joan Bennett 7 , Paul Bowyer 3 , Dan Chen 1 , Matthew Collins 2 , Richard Coulsen 8 , Robert Davies 2 , Paul S. Dyer 6 , Mark Farman 9 , Nadia Fedorova 1 , Natalie Fedorova 1 , Tamara V. Feldblyum 1 , Reinhard Fischer 10 , Nigel Fosker 2 , Audrey Fraser 2 , Jose L. Garcı ´a 11 , Maria J. Garcı ´a 12 , Arlette Goble 2 , Gustavo H. Goldman 13 , Katsuya Gomi 5 , Sam Griffith-Jones 2 , Ryan Gwilliam 2 , Brian Haas 1 , Hubertus Haas 14 , David Harris 2 , H. Horiuchi 15 , Jiaqi Huang 1 , Sean Humphray 2 , Javier Jime ´nez 12 , Nancy Keller 15 , Hoda Khouri 1 , Katsuhiko Kitamoto 16 , Tetsuo Kobayashi 17 , Sven Konzack 10 , Resham Kulkarni 1 , Toshitaka Kumagai 18 , Anne Lafton 19 , Jean-Paul Latge ´ 20 , Weixi Li 9 , Angela Lord 2 , Charles Lu 1 , William H. Majoros 1 , Gregory S. May 21 , Bruce L. Miller 22 , Yasmin Mohamoud 1 , Maria Molina 4 , Michel Monod 23 , Isabelle Mouyna 20 , Stephanie Mulligan 1 , Lee Murphy 2 , Susan O’Neil 2 , Ian Paulsen 1 , Miguel A. Pen ˜alva 11 , Mihaela Pertea 1 , Claire Price 2 , Bethan L. Pritchard 3 , Michael A. Quail 2 , Ester Rabbinowitsch 2 , Neil Rawlins 2 , Marie-Adele Rajandream 2 , Utz Reichard 24 , Hubert Renauld 2 , Geoffrey D. Robson 3 , Santiago Rodriguez de Co ´rdoba 11 , Jose M. Rodrı ´guez-Pen ˜a 4 , Catherine M. Ronning 1 , Simon Rutter 2 , Steven L. Salzberg 1 , Miguel Sanchez 12 , Juan C. Sa ´nchez-Ferrero 11 , David Saunders 2 , Kathy Seeger 2 , Rob Squares 2 , Steven Squares 2 , Michio Takeuchi 25 , Fredj Tekaia 20 , Geoffrey Turner 26 , Carlos R. Vazquez de Aldana 12 , Janice Weidman 1 , Owen White 1 , John Woodward 2 , Jae-Hyuk Yu 27 , Claire Fraser 1 , James E. Galagan 28 , Kiyoshi Asai 18 , Masayuki Machida 29 , Neil Hall 2 †, Bart Barrell 2 & David W. Denning 3 Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen 1–3 . Its conidia production is prolific, and so human respiratory tract exposure is almost constant 4 . A. fumigatus is isolated from human habitats 5 and vegetable compost heaps 6,7 . In immunocompromised individuals, the incidence of invasive infec- tion can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis 8 . Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4- megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence pro- vides an unparalleled resource for the future understanding of this remarkable fungus. The genome of A. fumigatus Af293 was sequenced by the whole- genome random sequencing method 9 augmented by optical map- ping 10 . Genome closure and quality standard attainment was accom- plished by directed sequencing and manual editing. (See Table 1 and Supplementary Fig. S1 for genome features.) Sequenced chromoso- mal arms extend from putative centromeres to the telomere and end in 7–21 tandem repeats of the sequence TTAGGG. The copy number of the mitochondrial genome relative to the nuclear genome is estimated to be 12 based on the redundancy in the assembled LETTERS 1 The Institute for Genomic Research, Rockville, Maryland 20850, and The George Washington University School of Medicine, Department of Biochemistry and Molecular Biology, 2300 Eye Street NW, Washington DC 20037, USA. 2 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK. 3 School of Medicine and Faculty of Life Sciences, The University of Manchester, Stopford Building, Manchester M13 9PT, UK. 4 Departmento Microbiologı ´a II. Universidad Complutense de Madrid 28040, Spain. 5 Tohoku University, 1-1 Tsutsumidori-Amamiyamachi Aoba-ku, Sendai 981-8555, Japan. 6 School of Biology, University of Nottingham, University Park, Nottingham NG7 2RD, UK. 7 Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA. 8 European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK. 9 Department of Plant Pathology, University of Kentucky, Lexington, Kentucky 40546-0312, USA. 10 Max Planck Institute for Terrestrial Microbiology, D-35043 Marburg, Germany. 11 Centro de Investigaciones Biolo ´gicas, CSIC, Madrid 28040, Spain. 12 Departmento Microbiologia y Genetica, Universidad de Salamanca, 37007 Salamanca, Spain. 13 Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Brazil. 14 Department of Molecular Biology, Innsbruck Medical University, A-6020 Innsbruck, Austria. 15 Department of Plant Pathology, University of Wisconsin at Madison, Madison, Wisconsin 53706, USA. 16 Department of Biotechnology, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. 17 Department of Biological Mechanisms and Functions, Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan. 18 Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan. 19 Unite ´ Postulante Biologie et Pathoge ´nicite ´ Fongiques, INRA USC 2019, Institut Pasteur, Paris 75015, France. 20 Unite ´ des Aspergillus, Institut Pasteur, Paris 75015, France. 21 Division of Pathology and Laboratory Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. 22 Departments of Microbiology, Molecular Biology and Biochemistry, Center for Reproductive Biology, University of Idaho, Moscow, Idaho 83844, USA. 23 Department of Dermatology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland. 24 Department of Bacteriology, Georg-August-University, D-37077 Gottingen, Germany. 25 Tokyo University of Agriculture and Technology, Saiwai-chou 3-5-8, Fuchu, Tokyo 183-0054, Japan. 26 Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield S10 2TN, UK. 27 Department of Food Microbiology and Toxicology, The University of Wisconsin, Madison, Wisconsin 53706, USA. 28 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA. 29 Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki 305-8566, Japan. †Present address: The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland 20850, USA. Vol 438|22/29 December 2005|doi:10.1038/nature04332 1151