Here’s what you’ll learn when you read this story:

• While codons (combinations of three nucleotides) may vary in which do what functions, a long-standing rule was that each codon serves one specific purpose.
• New evidence, however suggests that onemicrobe sometimes uses the codon UGA as a stop codon and sometimes use it to code for the amino acid pyrrolysine.
• The discovery of this “loosey-goosey” translation could help scientists better understand archaea in our bodies and improve treatments of diseases.

---

The building blocks of life are formed from a simple process: DNA is transcribed into RNA, which then becomes proteins. And all life follows the same instructions for how those proteins form—instructions based on 61 codons made of three nucleotides, all of which are combinations of the four nucleic acids named adenine (A), cytosine (C), guanine (G), and uracil (U).

These codons are typically assigned either to one of the 20 canonical amino acids or to what’s known as a stop codon (usually UAA, UAG, or UGA), the latter of which sends a signal to terminate protein-building and release the polypeptide chain. For decades, scientists have assumed that this process needs to be exact to avoid an imprecise genetic code. However, a new study—published in the journal Proceedings of the National Academy of Sciences (PNAS) and led by scientists at the University of California (UC) Berkeley—discovered that at least one archaea, a methane-producing microbe named Methanosarcina acetivorans, survives by utilizing a more “loosey-goosey” translation method.

“Objectively, ambiguity in the genetic code should be deleterious; you end up generating a random pool of proteins,” Dipti Nayak, senior author of the paper from UC Berkeley, said in a press statement. “But biological systems are more ambiguous than we give them credit to be and that ambiguity is actually a feature—it’s not a bug.”

The scientists theorize that this “ambiquity” allowed the microbe to introduce the uncommon amino acid, pyrrolysine, to create enzymes that break down certain foods. Although life varies when it comes to the number of amino acids and what codons code which ones (with some even being redundant), one thing is usually certain: A codon has only one meaning. That is, until now.

Pyrrolysine is widespread in methanogenic archaea, and lead study author Katie Shalvarjian (now a postdoctoral researcher at the Lawrence Livermore National Laboratory) noticed while studying these methanogenic organisms that, strangely enough, the UAG codon in M. acetivorans wasn’t always being interpreted as pyrrolysine.

“The UAG codon is like a fork in the road, where it can be interpreted either as a stop codon or as a pyrrolysine residue,” Shalvarjian said in a press statement.

“They’re flip-flopping back and forth between whether they should call this a stop or whether they should keep going by adding this new amino acid,” Nayak added. “They cannot decide. They just do both and they seem to be fine by making this random choice.”

Preliminary findings suggest that the archaea’s choice isn’t completely random. When the amino acid is flooding the cell, the microbe tends to interpret UAG as integrated pyrrolysine and turn it into the appropriate protein. However, when less of it was around, UAG often acted as a stop codon, which yields a different protein entirely.

This research connects to the future of human health in surprising ways. For example, the human body relies on archaea to remove methylamines and keep the liver healthy, so it’s important to understand this ambiguity in its molecular machinery. Additionally, scientists could experiment with introducing a similar level of imprecision into gene therapies, which could address maladies caused by premature stop codons (such as cystic fibrosis).

“This really opens the door to finding interesting ways to control how cells interpret stop codons,” Nayak said.

Darren lives in Portland, has a cat, and writes/edits about sci-fi and how our world works. You can find his previous stuff at Gizmodo and Paste if you look hard enough.