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 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.
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Deutschbauer
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Morgan N
authors.initials: MN
authors.lastname: Price
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Wetmore
authors.affiliation: Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA Energy Biosciences Institute, University of California, Berkeley, California, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Tarjan
authors.affiliation: Department of Bioengineering, University of California, Berkeley, California, USA.
authors.forename: Zhuchen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Shao
authors.affiliation: Earth Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA Energy Biosciences Institute, University of California, Berkeley, California, USA.
authors.forename: Dacia
authors.initials: D
authors.lastname: Leon
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA Energy Biosciences Institute, University of California, Berkeley, California, USA Department of Bioengineering, University of California, Berkeley, California, USA APArkin@lbl.gov skerker@berkeley.edu.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Arkin
authors.affiliation: Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA Energy Biosciences Institute, University of California, Berkeley, California, USA Department of Bioengineering, University of California, Berkeley, California, USA APArkin@lbl.gov skerker@berkeley.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Skerker
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D056084:Genetic Fitness; D009154:Mutation; D020592:Shewanella / Q000235:genetics / Q000378:metabolism*; D017355:Zymomonas / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins
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