The power of single-cell genomics: the mysterious SR1 bacteria have a unique genetic code
Thanks to Mitch Balish for calling my attention to this one.
SR1 bacteria are not exactly a household name, even among microbiologists. They were first discovered in contaminated aquifers, and since then they were found to be also in animal and insect guts, as well as in human mouths. They are even suspected of being a cause of periodontal disease. I should probably say here that SR1 is a whole phylum of bacteria, and not a single genus or species. The reason that they are not that well known is that their discovery was fairly recent.
Also, no one has ever actually seen or grown SR1.
Like 99% of the microbial world, SR1 cannot be cultured in the lab. Maybe they need the close association of other bacteria that provide nutrients or some sort of essential function that SR1 lack. (See the “Black Queen Hypothesis” on how members of multi-species bacterial communities provide essential functions to the community.) Our knowledge of SR1 comes from finding molecular species markers in environmental genomic studies. These markers give us an estimate of the prevalence of SR1 bacteria. The fact that we find them in certain types of environments tell us of their preferences for low oxygen. Some also are suspected to be free living, while those that are associated with humans and other animals are thought to be parasitic or commensal.
Characterizing bacteria by small fragments of genomic sequences is like walking in a forest and not seeing any animals. You only see strange tracks on the ground, and branches with clumps of fur that were scraped off several animals. Judging by the fur and tracks, you can tell that these may be animals you haven’t seen before. Even though you cannot observe the animals. you can lean some things about them: fur color an consistency can help you classify them in a certain mammalian family (only mammals have fur). The tracks and height of fur clumps can tell you the animals’ approximate size and weight. If the tracks are clawed, you may infer the mystery animals are carnivorous. If they are hooves, they are probably herbivorous. You can also infer their range, and perhaps an approximate number of individuals, and whether different subspecies likes to live in the hilly or the flat part of the forest. An occasional feather on the ground, or nest in the trees may tell you there are birds in th forest too. Still, you can’t learn much more than that there is a community of animals, and the approximate number of species and some basic traits they may have.
So a new study on the single-cell sequencing of SR1 is quite welcome: it’s a good trap for our unidentified animals, or removing the helmet from the Stig’s head. Metagenomics can provide a sample-based genetic picture of a microbial community, but can’t tell us of the structure of an individual bacterial genome. A single whole genome can inform us of what a bacterium can or can’t do, as an individual biological unit. So we can learn, for example, why members of SR1 cannot be cultured, or why they may be involved in periodontal disease.
A group from Oak Ridge National Laboratory, Yale University and the Joint Genome Institute have managed to do that. They isolated single cells of SR1 bacteria, and although the bacteria could not be cultured, their genomes could be sequenced. Once the researchers actually looked at the predicted genes, they found that they were uncharacteristically and unrealistically short. The UGA codon that normally signals the stop of protein translation, appeared with an alarmingly high frequency, cutting genes in the middle. This led them to think that the UGA codon may not actually be a stop codon. Searching the genome, they found a gene for tRNA that looks like a Glycine carrier, and had the ACU anticodon.
Bingo. The UGA codons in SR1 actually code for Glycine. An (almost) first. UGA for glycine were found before in mitichondria of a sea-squirt, but only there.
The genome the researchers sequenced is incomplete, but there are several other interesting things they found. One is no evidence of respiration-related genes, explaining why SR1 are found in oxygen-poor environments. Another oddity is a strange kind of RubisCO. RuBisCO is probably the most abundant protein on earth, and is the enzyme involved in the first major step of converting CO2 into sugars – something plants and phtosynthetic bacteria do. SR1 are not photosynthetic, and their RubisCO, although able to fix carbon, is actually involved in the breakdown of sugars. This ”re-purposing” of RubisCO is something that is found in archaea, but rarely in bacteria. Another first.
This study is exciting, because it shows the power of single-cell genomics. No matter how much metagenomics you do, you will still be left with an incomplete picture of the genomic data in your sample, and left guessing as to what individual species may be doing. With single-cell genomics, “complete picture” genomics is back, and it’s taking on the uncultured microbes.
Campbell, J., O’Donoghue, P., Campbell, A., Schwientek, P., Sczyrba, A., Woyke, T., Soll, D., & Podar, M. (2013). UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1303090110