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Pervasive translation in Mycobacterium tuberculosis

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 act...

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Autores principales: Smith, Carol, Canestrari, Jill G, Wang, Archer J, Champion, Matthew M, Derbyshire, Keith M, Gray, Todd A, Wade, Joseph T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094748/
https://www.ncbi.nlm.nih.gov/pubmed/35343439
http://dx.doi.org/10.7554/eLife.73980
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author Smith, Carol
Canestrari, Jill G
Wang, Archer J
Champion, Matthew M
Derbyshire, Keith M
Gray, Todd A
Wade, Joseph T
author_facet Smith, Carol
Canestrari, Jill G
Wang, Archer J
Champion, Matthew M
Derbyshire, Keith M
Gray, Todd A
Wade, Joseph T
author_sort Smith, Carol
collection PubMed
description 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.
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spelling pubmed-90947482022-05-12 Pervasive translation in Mycobacterium tuberculosis Smith, Carol Canestrari, Jill G Wang, Archer J Champion, Matthew M Derbyshire, Keith M Gray, Todd A Wade, Joseph T eLife Microbiology and Infectious Disease 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. eLife Sciences Publications, Ltd 2022-03-28 /pmc/articles/PMC9094748/ /pubmed/35343439 http://dx.doi.org/10.7554/eLife.73980 Text en https://creativecommons.org/publicdomain/zero/1.0/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 (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Microbiology and Infectious Disease
Smith, Carol
Canestrari, Jill G
Wang, Archer J
Champion, Matthew M
Derbyshire, Keith M
Gray, Todd A
Wade, Joseph T
Pervasive translation in Mycobacterium tuberculosis
title Pervasive translation in Mycobacterium tuberculosis
title_full Pervasive translation in Mycobacterium tuberculosis
title_fullStr Pervasive translation in Mycobacterium tuberculosis
title_full_unstemmed Pervasive translation in Mycobacterium tuberculosis
title_short Pervasive translation in Mycobacterium tuberculosis
title_sort pervasive translation in mycobacterium tuberculosis
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094748/
https://www.ncbi.nlm.nih.gov/pubmed/35343439
http://dx.doi.org/10.7554/eLife.73980
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