Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives

  1. Thomas J. Sharpton1,11,
  2. Jason E. Stajich1,
  3. Steven D. Rounsley2,
  4. Malcolm J. Gardner3,
  5. Jennifer R. Wortman4,
  6. Vinita S. Jordar5,
  7. Rama Maiti5,
  8. Chinnappa D. Kodira6,
  9. Daniel E. Neafsey6,
  10. Qiandong Zeng6,
  11. Chiung-Yu Hung7,
  12. Cody McMahan7,
  13. Anna Muszewska8,
  14. Marcin Grynberg8,
  15. M. Alejandra Mandel2,
  16. Ellen M. Kellner2,
  17. Bridget M. Barker2,
  18. John N. Galgiani9,
  19. Marc J. Orbach2,
  20. Theo N. Kirkland10,
  21. Garry T. Cole7,
  22. Matthew R. Henn6,
  23. Bruce W. Birren6 and
  24. John W. Taylor1
  1. 1 Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California 94720, USA;
  2. 2 Department of Plant Sciences, The University of Arizona, Tucson Arizona 85721, USA;
  3. 3 Department of Global Health, Seattle Biomedical Research Institute, Seattle, Washington 98109-5219, USA;
  4. 4 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
  5. 5 J. Craig Venter Institute, Rockville, Maryland 20850, USA;
  6. 6 Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
  7. 7 Department of Biology, The University of Texas at San Antonio, San Antonio, Texas 78249, USA;
  8. 8 Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw 02-106, Poland;
  9. 9 Valley Fever Center for Excellence, The University of Arizona, Tuscon, Arizona 85721, USA;
  10. 10 Department of Pathology, University of California at San Diego, La Jolla, California 92093, USA

    Abstract

    While most Ascomycetes tend to associate principally with plants, the dimorphic fungi Coccidioides immitis and Coccidioides posadasii are primary pathogens of immunocompetent mammals, including humans. Infection results from environmental exposure to Coccidiodies, which is believed to grow as a soil saprophyte in arid deserts. To investigate hypotheses about the life history and evolution of Coccidioides, the genomes of several Onygenales, including C. immitis and C. posadasii; a close, nonpathogenic relative, Uncinocarpus reesii; and a more diverged pathogenic fungus, Histoplasma capsulatum, were sequenced and compared with those of 13 more distantly related Ascomycetes. This analysis identified increases and decreases in gene family size associated with a host/substrate shift from plants to animals in the Onygenales. In addition, comparison among Onygenales genomes revealed evolutionary changes in Coccidioides that may underlie its infectious phenotype, the identification of which may facilitate improved treatment and prevention of coccidioidomycosis. Overall, the results suggest that Coccidioides species are not soil saprophytes, but that they have evolved to remain associated with their dead animal hosts in soil, and that Coccidioides metabolism genes, membrane-related proteins, and putatively antigenic compounds have evolved in response to interaction with an animal host.

    Footnotes

    • 11 Corresponding author.

      E-mail sharpton{at}berkeley.edu; fax (510) 642-4995.

    • [Supplemental material is available online at http://www.genome.org. The sequence data for C. immitis, C. posadasii, H. capsulatum, and U. reesii have been submitted to GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) under accession nos. AAEC02000000, ACFW00000000, AAJI01000000, and AAIW01000000, respectively.]

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.087551.108.

      • Received October 8, 2008.
      • Accepted May 12, 2009.
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