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For decades, biology has relied on one central assumption: the genetic code is precise. DNA is transcribed into RNA, RNA is translated into proteins, and each three-letter codon has a fixed meaning. But scientists now say at least one living organism doesn’t strictly follow that rule.A new study published in the Proceedings of the National Academy of Sciences (PNAS) reports that a methane-producing microbe can survive while using a far more flexible, or ambiguous, version of the genetic code. The research was led by scientists at the University of California, Berkeley.
How the genetic code is supposed to work
In most forms of life, proteins are built using instructions from 61 codons, each made up of three nucleotides, adenine (A), cytosine (C), guanine (G), and uracil (U). These codons correspond to 20 standard amino acids or signal the end of protein production through stop codons such as UAA, UAG, and UGA.Biologists have long believed this system must be exact. Any ambiguity, scientists assumed, would result in faulty proteins and be harmful to life.That assumption is now being challenged.
A microbe that bends the rules
The study focused on an archaea called Methanosarcina acetivorans, a methane-producing microbe. Researchers found that this organism can survive despite using what they describe as a “looser” translation process.“Objectively, ambiguity in the genetic code should be deleterious; you end up generating a random pool of proteins,” said Dipti Nayak, senior author of the study, in a UC Berkeley 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.”Scientists believe this ambiguity allows the microbe to incorporate pyrrolysine, a rare amino acid, into proteins that help it break down certain nutrients.
One codon, two meanings
What surprised researchers most was how M. acetivorans interprets the UAG codon. Traditionally, UAG acts as a stop signal, telling the cell to halt protein production. But in this microbe, it sometimes codes for pyrrolysine instead.“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,” said Katie Shalvarjian, the study’s lead author and now a postdoctoral researcher at Lawrence Livermore National Laboratory, 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.”
Why the choice isn’t entirely random
Early findings suggest the microbe’s decision depends on its internal environment. When pyrrolysine is abundant inside the cell, UAG is more likely to be read as that amino acid. When levels are low, the same codon often functions as a stop signal, producing a shorter and entirely different protein.This dual interpretation directly contradicts one of biology’s long-standing rules: that a codon has only one meaning.The implications extend beyond microbial biology. Archaea play an important role in the human body by removing methylamines and helping maintain liver health, making it critical to understand how their molecular machinery works.The findings may also influence future gene therapy research. Some genetic diseases, including cystic fibrosis, are caused by premature stop codons. Introducing controlled ambiguity into genetic translation could one day help bypass those errors.“This really opens the door to finding interesting ways to control how cells interpret stop codons,” Nayak said.
