Pervasive translation in Mycobacterium tuberculosis
- New York State Department of Health, United States
- University of Notre Dame, United States
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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Pervasive Translation in Mycobacterium tuberculosisEBI ArrayExpress E-MTAB-8039.
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Pervasive Translation in Mycobacterium tuberculosisEBI ArrayExpress E-MTAB-10695.
Article and author information
Author details
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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Pervasive translation in Mycobacterium tuberculosis
eLife 11:e73980.
https://doi.org/10.7554/eLife.73980
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