1. Microbiology and Infectious Disease

Pervasive translation in Mycobacterium tuberculosis

  1. Carol Smith
  2. Jill G Canestrari
  3. Archer J Wang
  4. Matthew M Champion
  5. Keith M Derbyshire  Is a corresponding author
  6. Todd A Gray  Is a corresponding author
  7. Joseph T Wade  Is a corresponding author
  1. New York State Department of Health, United States
  2. University of Notre Dame, United States
https://doi.org/10.7554/eLife.73980
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  1. Carol Smith
  2. Jill G Canestrari
  3. Archer J Wang
  4. Matthew M Champion
  5. Keith M Derbyshire
  6. Todd A Gray
  7. Joseph T Wade
(2022)
Pervasive translation in Mycobacterium tuberculosis
eLife 11:e73980.
https://doi.org/10.7554/eLife.73980
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Abstract

Most bacterial ORFs are identified by automated prediction algorithms. However, these algorithms often fail to identify ORFs lacking canonical features such as a length of >50 codons or the presence of an upstream Shine-Dalgarno sequence. Here, we use ribosome profiling approaches to identify actively translated ORFs in Mycobacterium tuberculosis. Most of the ORFs we identify have not been previously described, indicating that the M. tuberculosis transcriptome is pervasively translated. The newly described ORFs are predominantly short, with many encoding proteins of ≤50 amino acids. Codon usage of the newly discovered ORFs suggests that most have not been subject to purifying selection, and hence are unlikely to contribute to cell fitness. Nevertheless, we identify 90 new ORFs (median length of 52 codons) that bear the hallmarks of purifying selection. Thus, our data suggest that pervasive translation of short ORFs in Mycobacterium tuberculosis serves as a rich source for the evolution of new functional proteins.

Data availability

Raw Illumina sequencing data are available from the ArrayExpress and European Nucleotide Archive repositories with accession numbers E-MTAB-8039 and E-MTAB-10695. Raw mass spectrometry data are available through MassIVE, with exchange #MSV000087541. Reviewers can access the raw mass spectrometry data at ftp://MSV000087541@massive.ucsd.edu, password: sproteinTBPython code is available at https://github.com/wade-lab/Mtb_Ribo-RET.

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Author details

  1. Carol Smith

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    Competing interests
    No competing interests declared.

  2. Jill G Canestrari

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    Competing interests
    No competing interests declared.

  3. Archer J Wang

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    Competing interests
    No competing interests declared.

  4. Matthew M Champion

    Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, United States
    Competing interests
    No competing interests declared.

  5. Keith M Derbyshire

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    For correspondence
    keith.derbyshire@health.ny.gov
    Competing interests
    No competing interests declared.

  6. Todd A Gray

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    For correspondence
    todd.gray@health.ny.gov
    Competing interests
    No competing interests declared.

  7. Joseph T Wade

    Wadsworth Center, Division of Genetics, New York State Department of Health, Albany, United States
    For correspondence
    joseph.wade@gmail.com
    Competing interests
    Joseph T Wade, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9779-3160

Funding

National Institute of Allergy and Infectious Diseases (R21AI117158)

  • Keith M Derbyshire
  • Todd A Gray
  • Joseph T Wade

National Institute of Allergy and Infectious Diseases (R21AI119427)

  • Keith M Derbyshire
  • Todd A Gray
  • Joseph T Wade

National Institute of General Medical Sciences (R01GM139277)

  • Matthew M Champion
  • Keith M Derbyshire
  • Todd A Gray
  • Joseph T Wade

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Carol Smith
  2. Jill G Canestrari
  3. Archer J Wang
  4. Matthew M Champion
  5. Keith M Derbyshire
  6. Todd A Gray
  7. Joseph T Wade
(2022)
Pervasive translation in Mycobacterium tuberculosis
eLife 11:e73980.
https://doi.org/10.7554/eLife.73980

Share this article

https://doi.org/10.7554/eLife.73980

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