1. The Broad Institute of MIT and Harvard, 320 Charles Street, Cambridge, Massachusetts 02142, USA
2. The Institute for Genomic Research, Rockville, Maryland 20850, USA
3. Department of Computer Science, Stanford University, Stanford, California 94305, USA
4. Department of Environmental and Biomolecular Systems, Oregon Health & Science University, 20 000 NW Walker Road, Beaverton, Oregon 97006-8921, USA
5. Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK
6. Genetic Information Research Institute, 1925 Landings Drive, Mountain View, California 94043, USA
7. Institut de Génétique et Microbiologie, Institut Universitaire de France, Université Paris-Sud, UMR8621, 91405 Orsay Cedex, France
8. Department of Plant Pathology, Plant Science Building, 1405 Veteran's Drive, University of Kentucky, Lexington, Kentucky 40546-0312, USA
9. Plant Science Initiative and Department of Plant Pathology, University of Nebraska, Lincoln, Nebraska 68588, USA
10. Department of Molecular Microbiology and Genetics, Institute for Microbiology and Genetics, Georg-August-University Gottingen, Grisebachstr. 8, D-37077 Gottingen, Germany
11. Institut Pasteur, Unité Postulante Biologie et Pathogénicité Fongiques, INRA USC 2019, 75724 Paris Cedex 15, France
12. Institut Pasteur, Génopole-PF1, 75724 Paris Cedex 15, France
13. Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Brazil
14. Department of Biology, Texas A&M University, College Station, Texas 77843, USA
15. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK
16. John Innes Centre, Colney Lane, Norwich NR4 7UH, UK
17. Department of Food Microbiology and Toxicology, The University of Wisconsin-Madison, 1925 Willow Drive, Madison, Wisconsin 53706-1187, USA
18. Max Planck Institute for terrestrial Microbiology, D-35043 Marburg and Institute for Applied Biosiences at the University of Karlsruhe, D-76187 Karlsruhe, Germany
19. Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, USA
20. School of Biology, University Park, University of Nottingham, Nottingham NG7 2RD, UK
21. Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Ramiro de Maeztu 9, Madrid 28040, Spain
22. Department of Molecular Genetics, The Ohio State University, Columbus, Ohio 43210, USA
23. The University of Georgia, Department of Plant Biology, 2502 Plant Sciences, Athens, Georgia 30602-7271, USA
24. National Institute of Technology and Evaluation (NITE), 2-49-10 Nishihara, Shibuya-ku, Tokyo 151-0066, Japan
25. National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan
26. The George Washington University School of Medicine, Department of Biochemistry and Molecular Biology, 2300 Eye Street NW, Washington DC 20037, USA
27. Schools of Medicine and Biological Sciences, The University of Manchester, Stopford Building, Manchester M23 9PL, UK
28. Plant Science and Fungal Molecular Biology Research Group, School of Biological Sciences, Donnan Labs, The University of Liverpool, Liverpool L69 7ZD, UK
29. Department of Genetics, University of Melbourne, Parkville, Victoria 3010, Australia
30. Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, Idaho 83844-3052, USA

Correspondence to: James E. Galagan¹ Correspondence and requests for materials should be addressed to J.E.G. (Email: jgalag@mit.edu). The A. nidulans genome sequence has been deposited at DDBJ/EMBL/GenBank under the project accession AACD00000000.

Abstract

The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

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