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A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome

Author

Listed:
  • Poonam Chitale

    (Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School)

  • Alexander D. Lemenze

    (Rutgers—The State University of New Jersey)

  • Emily C. Fogarty

    (University of Chicago
    University of Chicago)

  • Avi Shah

    (Rutgers University – New Jersey Medical School
    Rutgers University- New Jersey Medical School)

  • Courtney Grady

    (Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School)

  • Aubrey R. Odom-Mabey

    (Boston University School of Medicine and Bioinformatics Program, Boston University
    Boston University)

  • W. Evan Johnson

    (Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School)

  • Jason H. Yang

    (Rutgers University – New Jersey Medical School
    Rutgers University- New Jersey Medical School)

  • A. Murat Eren

    (Helmholtz Institute for Functional Marine Biodiversity (HIFMB)
    Bay Paul Center, Marine Biological Laboratory)

  • Roland Brosch

    (Université Paris Cité, Unit for Integrated Mycobacterial Pathogenomics)

  • Pradeep Kumar

    (Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School)

  • David Alland

    (Rutgers University – New Jersey Medical School
    Rutgers University – New Jersey Medical School)

Abstract

H37Rv is the most widely used Mycobacterium tuberculosis strain, and its genome is globally used as the M. tuberculosis reference sequence. Here, we present Bact-Builder, a pipeline that uses consensus building to generate complete and accurate bacterial genome sequences and apply it to three independently cultured and sequenced H37Rv aliquots of a single laboratory stock. Two of the 4,417,942 base-pair long H37Rv assemblies are 100% identical, with the third differing by a single nucleotide. Compared to the existing H37Rv reference, the new sequence contains ~6.4 kb additional base pairs, encoding ten new regions that include insertions in PE/PPE genes and new paralogs of esxN and esxJ, which are differentially expressed compared to the reference genes. New sequencing and de novo assemblies with Bact-Builder confirm that all 10 regions, plus small additional polymorphisms, are also present in the commonly used H37Rv strains NR123, TMC102, and H37Rv1998. Thus, Bact-Builder shows promise as an improved method to perform accurate and reproducible de novo assemblies of bacterial genomes, and our work provides important updates to the primary M. tuberculosis reference genome.

Suggested Citation

  • Poonam Chitale & Alexander D. Lemenze & Emily C. Fogarty & Avi Shah & Courtney Grady & Aubrey R. Odom-Mabey & W. Evan Johnson & Jason H. Yang & A. Murat Eren & Roland Brosch & Pradeep Kumar & David Al, 2022. "A comprehensive update to the Mycobacterium tuberculosis H37Rv reference genome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34853-x
    DOI: 10.1038/s41467-022-34853-x
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    References listed on IDEAS

    as
    1. S. T. Cole & R. Brosch & J. Parkhill & T. Garnier & C. Churcher & D. Harris & S. V. Gordon & K. Eiglmeier & S. Gas & C. E. Barry & F. Tekaia & K. Badcock & D. Basham & D. Brown & T. Chillingworth & R., 1998. "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence," Nature, Nature, vol. 393(6685), pages 537-544, June.
    2. S. T. Cole & R. Brosch & J. Parkhill & T. Garnier & C. Churcher & D. Harris & S. V. Gordon & K. Eiglmeier & S. Gas & C. E. Barry & F. Tekaia & K. Badcock & D. Basham & D. Brown & T. Chillingworth & R., 1998. "Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence," Nature, Nature, vol. 396(6707), pages 190-190, November.
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