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Title: Towards an informative mutant phenotype for every bacterial gene

Journal Article · · Journal of Bacteriology
DOI:https://doi.org/10.1128/JB.01836-14· OSTI ID:1215653
 [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)

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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1215653
Journal Information:
Journal of Bacteriology, Vol. 196, Issue 20; ISSN 0021-9193
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 39 works
Citation information provided by
Web of Science

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Synthetic and systems biology for microbial production of commodity chemicals journal April 2016
Nitro sulfonyl fluorides are a new pharmacophore for the development of antibiotics journal January 2018
Essential genome of Pseudomonas aeruginosa in cystic fibrosis sputum journal March 2015
The essential gene set of a photosynthetic organism journal October 2015
Use of genetic and chemical synthetic lethality as probes of complexity in bacterial cell systems journal October 2017
The Extraintestinal Pathogenic Escherichia coli Factor RqlI Constrains the Genotoxic Effects of the RecQ-Like Helicase RqlH journal December 2015
A Markerless Method for Genome Engineering in Zymomonas mobilis ZM4 journal October 2019
Mutant phenotypes for thousands of bacterial genes of unknown function journal May 2018
A Comparison of the Costs and Benefits of Bacterial Gene Expression journal July 2016
Rapid Quantification of Mutant Fitness in Diverse Bacteria by Sequencing Randomly Bar-Coded Transposons journal May 2015
Complete genome sequence and the expression pattern of plasmids of the model ethanologen Zymomonas mobilis ZM4 and its xylose-utilizing derivatives 8b and 2032 journal May 2018
Prediction and characterization of promoters and ribosomal binding sites of Zymomonas mobilis in system biology era journal March 2019
A Comparison of the Costs and Benefits of Bacterial Gene Expression journal October 2016