Article

Nature 406, 477-483 (3 August 2000) | doi:10.1038/35020000; Received 3 April 2000; Accepted 18 May 2000

DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae

John F. Heidelberg1, Jonathan A. Eisen1, William C. Nelson1, Rebecca A. Clayton, Michelle L. Gwinn1, Robert J. Dodson1, Daniel H. Haft1, Erin K. Hickey1, Jeremy D. Peterson1, Lowell Umayam1, Steven R. Gill1, Karen E. Nelson1, Timothy D. Read1, Hervé Tettelin1, Delwood Richardson1, Maria D. Ermolaeva1, Jessica Vamathevan1, Steven Bass1, Haiying Qin1, Ioana Dragoi1, Patrick Sellers1, Lisa McDonald1, Teresa Utterback1, Robert D. Fleishmann1, William C. Nierman1, Owen White1, Steven L. Salzberg1, Hamilton O. Smith1,2, Rita R. Colwell3, John J. Mekalanos4, J. Craig Venter1,2 and Claire M. Fraser1

  1. The Institute for Genomic Research , 9712 Medical Center Drive, Rockville, Maryland 20850, USA
  2. Center of Marine Biotechnology, University of Maryland Biotechnology Institute, 701 East Pratt Street, Baltimore, Maryland 21202, USA, and
  3. Department of Cell and Molecular Biology, University of Maryland , College Park, Maryland 20742, USA
  4. Harvard Medical School, Department of Microbiology and Molecular Genetics, 200 Longwood Avenue , Boston, Massachusetts 02115, USA
  5. Present address: Celera Genomics, 45 West Gude Drive, Rockville, Maryland 20850, USA

Correspondence to: Claire M. Fraser1 Correspondence and requests for materials should be addressed to C.M.F. (e-mail: Email: gvc@tigr.org). The annotated genome sequence and the gene family alignments are available at left fencehttp://www.tigr.org/tbd/mdbright fence. The sequences have been deposited in GenBank with accession number AE003852 (chromosome 1) and AE003853 (chromosome 2).

Here we determine the complete genomic sequence of the Gram negative, gamma-Proteobacterium Vibrio cholerae El Tor N16961 to be 4,033,460 base pairs (bp). The genome consists of two circular chromosomes of 2,961,146 bp and 1,072,314 bp that together encode 3,885 open reading frames. The vast majority of recognizable genes for essential cell functions (such as DNA replication, transcription, translation and cell-wall biosynthesis) and pathogenicity (for example, toxins, surface antigens and adhesins) are located on the large chromosome. In contrast, the small chromosome contains a larger fraction (59%) of hypothetical genes compared with the large chromosome (42%), and also contains many more genes that appear to have origins other than the gamma-Proteobacteria. The small chromosome also carries a gene capture system (the integron island) and host 'addiction' genes that are typically found on plasmids; thus, the small chromosome may have originally been a megaplasmid that was captured by an ancestral Vibrio species. The V. cholerae genomic sequence provides a starting point for understanding how a free-living, environmental organism emerged to become a significant human bacterial pathogen.

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