Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen1-3. Its conidia production is prolific, and so human respiratory tract exposure is almost constant4. A. fumigatus is isolated from human habitats 5 and vegetable compost heaps6,7. In immunocompromised individuals, the incidence of invasive infection 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 sinusitis8. 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 provides an unparalleled resource for the future understanding of this remarkable fungus.
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Acknowledgements Initial work was funded by the Fungal Research Trust and Burroughs Wellcome Fund. Major funding came from the National Institute of Allergy and Infectious Diseases (NIAID), the Wellcome Trust and the Fondo de Investigaciones Sanitarias. Construction of the Af293 microarray was funded by NIAID. Additional BAC end sequencing was funded internally by the Institut Pasteur. We thank D. Dixon, C. Caulcott, V. McGovern, P. Goodwin and J.-L. Rodriguez-Tudela for their support and encouragement during this project. We also thank C. Staben of the University of Kentucky for intellectual assistance and script development.
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