With these charged alternative transfer RNAs in hand, the researchers confirmed that they were ignored by normal ribosomes. But if you used a ribosome with the corresponding changes that restored base pairing, it would happily make a protein using them. So, the researchers had two different populations of transfer RNAs, each compatible with a different population of ribosomes.
They designed a separate genetic code and used the alternative transfer RNAs to implement it. They then designed a messenger RNA that could be translated by both genetic codes, but would produce different proteins depending on which code was being used. They then put together a mixture of both populations of transfer RNAs, both populations of ribosomes, and all the chemicals needed to get translation to work.
Two different proteins were produced. So, both populations of ribosomes latched onto the messenger RNA but used different populations of transfer RNAs to make a protein using the messenger. And since the two populations implemented different genetic codes, the two populations of ribosomes made different proteins.
This is really cool.
It also might be practically useful. After all, it’s extremely difficult to mess with the genetic code, because every protein in the cell depends on it. If that code keeps working happily while you mess with a second genetic code, then the cell will potentially be quite a bit happier.
Potentially. The researchers only do this work in a mixture of proteins and chemicals isolated from cells; they don’t try it in actual cells. And, to be clear, it might cause problems there. After all, the alternative ribosome would still try to translate any messenger RNAs that it comes across but will use the wrong genetic code, likely producing lots of truncated or malformed proteins. Collectively, these could interfere enough with normal processes to kill the cell.
I don’t see an obvious way around this problem. But I wasn’t clever enough to realize that having two genetic codes operating in parallel was possible, so some sharp biologist may ultimately find a way around it.
Nature, 2026. DOI: 10.1038/s41586-026-10949-y (About DOIs).