Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 14, Pages 5540-5545Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1303090110
Keywords
aminoacyl-tRNA synthetase; oral microbiome; single-cell sequencing
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Funding
- National Institutes of Health [R01 HG004857, GM22854]
- Defense Advanced Research Projects Agency [N660-12-C-4020]
- Oak Ridge National Laboratory (managed by the University of Tennessee-Battelle) via the US Department of Energy [DE-AC05-00OR22725]
- US Department of Energy Joint Genome Institute
- Department of Energy [DE-AC02-05CH11231]
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The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(UCA)(Gly) with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(UCA)(Gly) with glycine in vitro with similar activity compared with normal tRNA(UCC)(Gly). Coexpression of SR1 glycyl-tRNA synthetase and tRNA(UCA)(Gly) in Escherichia coli yields significant beta-galactosidase activity in vivo from a lacZ gene containing an inframe TGA codon. Comparative genomic analysis with Human Micro-biome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.
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