Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control

  1. Steven D. Rounsley7
  1. 1 Broad Institute, Cambridge, Massachusetts 02142, USA;
  2. 2 Department of Veterinary Molecular Biosciences, Montana State University, Bozeman, Montana 59717, USA;
  3. 3 The Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA;
  4. 4 Plant Pathology and Microbiology, University of California, Riverside, California 92521, USA;
  5. 5 Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California 94720, USA;
  6. 6 Department of Biology, The University of Texas at San Antonio, San Antonio, Texas 78249, USA;
  7. 7 School of Plant Sciences, The University of Arizona, Tucson, Arizona 85721, USA;
  8. 8 Valley Fever Center for Excellence, The University of Arizona, Tucson, Arizona 85724, USA;
  9. 9 Department of Pathology, University of California at San Diego, La Jolla, California 92093, USA

    1. ↵10 These authors contributed equally to this work.

    Abstract

    We have sequenced the genomes of 18 isolates of the closely related human pathogenic fungi Coccidioides immitis and Coccidioides posadasii to more clearly elucidate population genomic structure, bringing the total number of sequenced genomes for each species to 10. Our data confirm earlier microsatellite-based findings that these species are genetically differentiated, but our population genomics approach reveals that hybridization and genetic introgression have recently occurred between the two species. The directionality of introgression is primarily from C. posadasii to C. immitis, and we find more than 800 genes exhibiting strong evidence of introgression in one or more sequenced isolates. We performed PCR-based sequencing of one region exhibiting introgression in 40 C. immitis isolates to confirm and better define the extent of gene flow between the species. We find more coding sequence than expected by chance in the introgressed regions, suggesting that natural selection may play a role in the observed genetic exchange. We find notable heterogeneity in repetitive sequence composition among the sequenced genomes and present the first detailed genome-wide profile of a repeat-induced point mutation (RIP) process distinctly different from what has been observed in Neurospora. We identify promiscuous HLA-I and HLA-II epitopes in both proteomes and discuss the possible implications of introgression and population genomic data for public health and vaccine candidate prioritization. This study highlights the importance of population genomic data for detecting subtle but potentially important phenomena such as introgression.

    Footnotes

    • Received December 21, 2009.
    • Accepted April 28, 2010.
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    1. Published in Advance June 1, 2010, doi: 10.1101/gr.103911.109 Genome Res. 20: 938-946 Copyright © 2010 by Cold Spring Harbor Laboratory Press

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