Journal
NATURE
Volume 557, Issue 7706, Pages 503-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-018-0124-0
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Funding
- NIH S10 Instrumentation Grants [S10RR029668, S10RR027303, OD018174]
- DOE Joint Genome Institute
- College of Biological Sciences UCDNA Sequencing Facility (UC Davis)
- Institute for Genomics Sciences (University of Maryland)
- Office of Science, Office of Biological and Environmental Research of the US Department of Energy [DE-AC02-05CH11231]
- Laboratory Directed Research and Development (LDRD) from Berkeley Laboratory by Office of Science of the US Department of Energy [DE-AC02-05CH11231]
- Community Science Project from the Joint Genome Institute
- Office of Science of the US Department of Energy [DE-AC02-05CH11231]
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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. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.
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