In a freshwater pond ciliate, the codon UAA, normally a stop signal, specifies the amino acid lysine, and UAG, also normally a stop signal, specifies glutamic acid. UGA still ends translation. The finding, reported in PLOS Genetics on October 5, 2023, came from sequencing work that was not designed to look for a new code. It breaks an expectation that UAA and UAG keep linked meanings, but it does not show that the standard genetic code is unstable across life.
What the standard genetic code does with stop codons
Proteins are built from instructions carried in messenger RNA. The code is read three letters at a time, and each three-letter unit, called a codon, usually specifies one amino acid. Three codons are different: UAA, UAG, and UGA tell the cell’s protein-making machinery to stop adding amino acids and release the finished chain.
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The third position of a codon is the “wobble” position, where pairing with transfer RNA (tRNA) is looser. UAA and UAG share their first two letters and differ only at the third. That similarity is why biologists have long assumed the two stop codons are tied together: when one is reassigned in a variant code, the other usually changes too, or keeps the same job.
How the ciliate turned up
The organism is a ciliate, a single-celled eukaryote with hair-like structures, recorded as Oligohymenophorea sp. PL0344. It was collected from a freshwater pond at Oxford University Parks in England. The team could not establish a stable long-term culture of it, so the study worked with small pools of cells and low-input sequencing methods.
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The discovery was incidental. Jamie McGowan, the lead author and a researcher at the Earlham Institute, described the organism’s selection as a matter of chance. In a news account from the Earlham Institute, he said: “It’s sheer luck we chose this protist to test our sequencing pipeline, and it just shows what’s out there, highlighting just how little we know about the genetics of protists.”
When the genome and transcriptome data were compared with conserved protein sequences, some in-frame UAA and UAG codons sat where the protein alignments pointed to lysine and glutamic acid. That pattern is what prompted the closer analysis.
The reassignment in plain terms
The table below sets the reported assignments for PL0344 against the standard code for the three stop codons.
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| Codon (RNA) | Standard code | PL0344 (as reported in the 2023 paper) |
|---|---|---|
| UAA | Stop | Lysine |
| UAG | Stop | Glutamic acid |
| UGA | Stop | Stop |
The surprise is not that a stop codon can carry an amino acid meaning, since other variant codes are known. It is that UAA and UAG, which were expected to move together, specify two different amino acids here. The authors read this as evidence that the coupling constraint can be overcome.
The numbers behind the claim
The claim rests on sequence analyses from this one organism. The authors checked internal codons at conserved protein positions, where the amino acid is predictable from related proteins:
| Codon examined | Internal codons at conserved sites | Matching the proposed amino acid |
|---|---|---|
| UAA (lysine) | 87 | 74 (85%) |
| UAG (glutamic acid) | 63 | 56 (89%) |
These are counts from the 2023 PLOS Genetics paper’s sequence analyses. They describe how well the proposed assignments fit conserved positions in this organism. They are not estimates of how common such codes are across organisms.
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Suppressor tRNAs and the downstream UGA question
Candidate tRNAs that could read the reassigned codons
The study also reports 23 putative suppressor tRNA genes: 12 predicted to carry a UUA anticodon and 10 predicted to carry a CUA anticodon. Anticodons with those sequences would be expected to pair with UAA and UAG codons, which is why they are the candidates that could decode the reassigned codons. These are predictions from gene sequences, not measured tRNA activity.
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1Fix the driver behind crashes, sound loss and screen glitches2Repair Windows errors before they cause bigger problems3Scan for outdated or missing drivers - takes under a minuteUGA codons after genes
UGA codons were enriched in the 3′ untranslated regions immediately downstream of genes. The authors propose that these nearby stop signals could limit the consequences when translation reads past a stop codon (readthrough). That is a proposed function, based on where the codons sit. The paper does not demonstrate the mechanism.
What the study does not establish
The paper does not establish the evolutionary sequence by which the code changed. It also does not report direct observation of the proteins made from these codons, so the amino acid assignments rest on sequence evidence and candidate tRNA genes rather than on protein-level measurement.
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Is this a one-off? The 2024 follow-up
A 2024 PLOS Genetics study found more UAG reassignments in ciliates. Three uncultivated species identified in TARA Oceans eukaryotic metagenome data were predicted to use UAG for leucine. Two other species, Hartmannula sinica and Trochilia petrani, were predicted to use UAG for glutamine. That study inferred three independent code-change events and found UAA remained the preferred stop codon in the taxa it sampled.
| Comparison point | PL0344 (2023 study) | Ciliates in the 2024 study |
|---|---|---|
| Reassigned stop codon | UAA and UAG | UAG |
| Amino acid assigned | UAA to lysine; UAG to glutamic acid | UAG to leucine (three species) or glutamine (two species) |
| Does UAA remain a stop? | No | Yes, in the sampled taxa |
| Source of evidence | Genome and transcriptome data from an uncultured organism, using small pools of cells | Metagenome data (three species) and genome-based predictions (two species) |
| Number of independent changes | Not stated as a separate count | Three independent events inferred |
The two studies describe a related pattern, but PL0344’s code is not the same as the leucine and glutamine assignments found later. The overlap is in the idea that UAG can be reassigned in ciliates.
What the discovery changes, and what it does not
The result shows that the link between UAA and UAG is not an absolute rule of translation. It adds a documented case in which the two stop codons carry different amino acids, which gives researchers a concrete example to test ideas about how genetic codes shift.
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It does not show that the standard code is breaking down. The standard code remains highly conserved across most known organisms. Ciliates are a notable group in which variant codes have been documented, and PL0344 is one of them. The McGowan team’s own framing points in the same direction: “Scientists attempt to engineer new genetic codes — but they are also out there in nature. There are fascinating things we can find, if we look for them. Or, in this case, when we are not looking for them.”
- The reassignment is documented in one organism from a single pond, based on sequence and candidate tRNA evidence.
- The downstream UGA role is a proposal, not a demonstrated mechanism.
- The 2024 study shows UAG reassignments in other ciliates, with different amino acids, which points to repeated evolutionary experiments rather than one isolated oddity.
For readers interested in the basics of how codons map to amino acids, a general genetics textbook covering translation is a sound background source. It is not required to follow this story.
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