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Title: Mutant phenotypes for thousands of bacterial genes of unknown function

Abstract

One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Lastly, our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [2];  [4];  [1];  [1] more »;  [5];  [5] « less
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Univ. of Missouri, Columbia, MO (United States)
  3. Univ. of California, San Diego, CA (United States)
  4. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Merced, CA (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1457011
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 557; Journal Issue: 7706; Related Information: © 2018 Macmillan Publishers Ltd., part of Springer Nature.; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Price, Morgan N., Wetmore, Kelly M., Waters, R. Jordan, Callaghan, Mark, Ray, Jayashree, Liu, Hualan, Kuehl, Jennifer V., Melnyk, Ryan A., Lamson, Jacob S., Suh, Yumi, Carlson, Hans K., Esquivel, Zuelma, Sadeeshkumar, Harini, Chakraborty, Romy, Zane, Grant M., Rubin, Benjamin E., Wall, Judy D., Visel, Axel, Bristow, James, Blow, Matthew J., Arkin, Adam P., and Deutschbauer, Adam M. Mutant phenotypes for thousands of bacterial genes of unknown function. United States: N. p., 2018. Web. doi:10.1038/s41586-018-0124-0.
Price, Morgan N., Wetmore, Kelly M., Waters, R. Jordan, Callaghan, Mark, Ray, Jayashree, Liu, Hualan, Kuehl, Jennifer V., Melnyk, Ryan A., Lamson, Jacob S., Suh, Yumi, Carlson, Hans K., Esquivel, Zuelma, Sadeeshkumar, Harini, Chakraborty, Romy, Zane, Grant M., Rubin, Benjamin E., Wall, Judy D., Visel, Axel, Bristow, James, Blow, Matthew J., Arkin, Adam P., & Deutschbauer, Adam M. Mutant phenotypes for thousands of bacterial genes of unknown function. United States. doi:10.1038/s41586-018-0124-0.
Price, Morgan N., Wetmore, Kelly M., Waters, R. Jordan, Callaghan, Mark, Ray, Jayashree, Liu, Hualan, Kuehl, Jennifer V., Melnyk, Ryan A., Lamson, Jacob S., Suh, Yumi, Carlson, Hans K., Esquivel, Zuelma, Sadeeshkumar, Harini, Chakraborty, Romy, Zane, Grant M., Rubin, Benjamin E., Wall, Judy D., Visel, Axel, Bristow, James, Blow, Matthew J., Arkin, Adam P., and Deutschbauer, Adam M. Wed . "Mutant phenotypes for thousands of bacterial genes of unknown function". United States. doi:10.1038/s41586-018-0124-0. https://www.osti.gov/servlets/purl/1457011.
@article{osti_1457011,
title = {Mutant phenotypes for thousands of bacterial genes of unknown function},
author = {Price, Morgan N. and Wetmore, Kelly M. and Waters, R. Jordan and Callaghan, Mark and Ray, Jayashree and Liu, Hualan and Kuehl, Jennifer V. and Melnyk, Ryan A. and Lamson, Jacob S. and Suh, Yumi and Carlson, Hans K. and Esquivel, Zuelma and Sadeeshkumar, Harini and Chakraborty, Romy and Zane, Grant M. and Rubin, Benjamin E. and Wall, Judy D. and Visel, Axel and Bristow, James and Blow, Matthew J. and Arkin, Adam P. and Deutschbauer, Adam M.},
abstractNote = {One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Lastly, our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.},
doi = {10.1038/s41586-018-0124-0},
journal = {Nature (London)},
number = 7706,
volume = 557,
place = {United States},
year = {2018},
month = {5}
}

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