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

Journal Article · · Nature (London)
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  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)
+ Show Author Affiliations

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.

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:
1457011
Journal Information:
Nature (London), Vol. 557, Issue 7706; Related Information: © 2018 Macmillan Publishers Ltd., part of Springer Nature.; ISSN 0028-0836
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 220 works
Citation information provided by
Web of Science

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Cited By (14)

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Oxidative Pathways of Deoxyribose and Deoxyribonate Catabolism journal February 2019
Unsupervised Learning Approach for Comparing Multiple Transposon Insertion Sequencing Studies journal February 2019
Salvage of the 5-deoxyribose byproduct of radical SAM enzymes journal August 2018
Changes in the genetic requirements for microbial interactions with increasing community complexity journal September 2018
Exploring the Evolution of Virulence Factors through Bioinformatic Data Mining journal May 2019
Metabolic network percolation quantifies biosynthetic capabilities across the human oral microbiome journal June 2019
The selective pressures on the microbial community in a metal-contaminated aquifer journal December 2018
Genome-driven cell engineering review: in vivo and in silico metabolic and genome engineering journal June 2019
Low mutational load and high mutation rate variation in gut commensal bacteria journal March 2020
Transposon-insertion sequencing screens unveil requirements for EHEC growth and intestinal colonization journal August 2019
Absolute Measurements of mRNA Translation in Caulobacter crescentus Reveal Important Fitness Costs of Vitamin B 12 Scavenging journal May 2019
Environmental conditions shape the nature of a minimal bacterial genome journal July 2019
BOFdat: Generating biomass objective functions for genome-scale metabolic models from experimental data journal April 2019

Figures / Tables (9)

Figure 1(p. 32)figure Figure 1
Figure 2(p. 33)figure Figure 2
Figure 3(p. 34)figure Figure 3
Figure 4(p. 35)figure Figure 4
Supplementary Figure 1(p. 39)figure Supplementary Figure 1
Supplementary Figure 2(p. 40)figure Supplementary Figure 2
Supplementary Figure 3(p. 41)figure Supplementary Figure 3
Supplementary Figure 4(p. 42)figure Supplementary Figure 4
Supplementary Figure 5(p. 43)figure Supplementary Figure 5

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