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Title: Towards an informative mutant phenotype for every bacterial gene

Abstract

Mutant phenotypes provide strong clues to the functions of the underlying genes and could allow annotation of the millions of sequenced yet uncharacterized bacterial genes. However, it is not known how many genes have a phenotype under laboratory conditions, how many phenotypes are biologically interpretable for predicting gene function, and what experimental conditions are optimal to maximize the number of genes with a phenotype. To address these issues, we measured the mutant fitness of 1,586 genes of the ethanol-producing bacterium Zymomonas mobilis ZM4 across 492 diverse experiments and found statistically significant phenotypes for 89% of all assayed genes. Thus, in Z. mobilis, most genes have a functional consequence under laboratory conditions. We demonstrate that 41% of Z. mobilis genes have both a strong phenotype and a similar fitness pattern (cofitness) to another gene, and are therefore good candidates for functional annotation using mutant fitness. Among 502 poorly characterized Z. mobilis genes, we identified a significant cofitness relationship for 174. For 57 of these genes without a specific functional annotation, we found additional evidence to support the biological significance of these gene-gene associations, and in 33 instances, we were able to predict specific physiological or biochemical roles for the poorly characterizedmore » genes. Last, we identified a set of 79 diverse mutant fitness experiments in Z. mobilis that are nearly as biologically informative as the entire set of 492 experiments. Therefore, our work provides a blueprint for the functional annotation of diverse bacteria using mutant fitness.« less

Authors:
 [1];  [1];  [1];  [2];  [3];  [1];  [2];  [2];  [2]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, Berkeley, CA (United States)
  3. Univ. of California, Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1215653
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Bacteriology
Additional Journal Information:
Journal Volume: 196; Journal Issue: 20; Journal ID: ISSN 0021-9193
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Deutschbauer, Adam, Price, Morgan N., Wetmore, Kelly M., Tarjan, Daniel R., Xu, Zhuchen, Shao, Wenjen, Leon, Dacia, Arkin, Adam P., and Skerker, Jeffrey M. Towards an informative mutant phenotype for every bacterial gene. United States: N. p., 2014. Web. doi:10.1128/JB.01836-14.
Deutschbauer, Adam, Price, Morgan N., Wetmore, Kelly M., Tarjan, Daniel R., Xu, Zhuchen, Shao, Wenjen, Leon, Dacia, Arkin, Adam P., & Skerker, Jeffrey M. Towards an informative mutant phenotype for every bacterial gene. United States. https://doi.org/10.1128/JB.01836-14
Deutschbauer, Adam, Price, Morgan N., Wetmore, Kelly M., Tarjan, Daniel R., Xu, Zhuchen, Shao, Wenjen, Leon, Dacia, Arkin, Adam P., and Skerker, Jeffrey M. Mon . "Towards an informative mutant phenotype for every bacterial gene". United States. https://doi.org/10.1128/JB.01836-14. https://www.osti.gov/servlets/purl/1215653.
@article{osti_1215653,
title = {Towards an informative mutant phenotype for every bacterial gene},
author = {Deutschbauer, Adam and Price, Morgan N. and Wetmore, Kelly M. and Tarjan, Daniel R. and Xu, Zhuchen and Shao, Wenjen and Leon, Dacia and Arkin, Adam P. and Skerker, Jeffrey M.},
abstractNote = {Mutant phenotypes provide strong clues to the functions of the underlying genes and could allow annotation of the millions of sequenced yet uncharacterized bacterial genes. However, it is not known how many genes have a phenotype under laboratory conditions, how many phenotypes are biologically interpretable for predicting gene function, and what experimental conditions are optimal to maximize the number of genes with a phenotype. To address these issues, we measured the mutant fitness of 1,586 genes of the ethanol-producing bacterium Zymomonas mobilis ZM4 across 492 diverse experiments and found statistically significant phenotypes for 89% of all assayed genes. Thus, in Z. mobilis, most genes have a functional consequence under laboratory conditions. We demonstrate that 41% of Z. mobilis genes have both a strong phenotype and a similar fitness pattern (cofitness) to another gene, and are therefore good candidates for functional annotation using mutant fitness. Among 502 poorly characterized Z. mobilis genes, we identified a significant cofitness relationship for 174. For 57 of these genes without a specific functional annotation, we found additional evidence to support the biological significance of these gene-gene associations, and in 33 instances, we were able to predict specific physiological or biochemical roles for the poorly characterized genes. Last, we identified a set of 79 diverse mutant fitness experiments in Z. mobilis that are nearly as biologically informative as the entire set of 492 experiments. Therefore, our work provides a blueprint for the functional annotation of diverse bacteria using mutant fitness.},
doi = {10.1128/JB.01836-14},
journal = {Journal of Bacteriology},
number = 20,
volume = 196,
place = {United States},
year = {Mon Aug 11 00:00:00 EDT 2014},
month = {Mon Aug 11 00:00:00 EDT 2014}
}

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