The belief that the genetic code is almost universal has been unsettled by a recent discovery in archaea. A study published in Science shows that a DNA sequence normally read as a “stop” signal during protein synthesis is, in some archaea, consistently read as a signal to add a rare amino acid. The finding reshapes how scientists understand genetic coding and carries implications for biotechnology and protein engineering.
How the genetic code normally works
Proteins are assembled by reading DNA in units of three bases, known as codons. These codons correspond to amino acids, the building blocks of proteins. Out of the 64 possible codons, 61 usually encode 20 common amino acids. The remaining three act as stop codons, signalling the cellular machinery to end protein synthesis. This system, deciphered by the late 1960s, has long been regarded as one of biology’s most conserved rules.
Rare exceptions to a universal rule
Although the genetic code is largely shared across life forms, a few deviations are known. In some bacteria, a codon that usually signals “stop” can encode an amino acid instead. In humans, for instance, one stop codon can be reinterpreted to insert selenocysteine in a small number of specialised proteins. In certain archaea, the stop codon TAG was already known to occasionally encode another rare amino acid, pyrrolysine (Pyl), but only in a handful of enzymes.
A genome-wide reassignment in archaea
The new study shows that this reassignment can be far more extensive. Researchers identified archaea in which the TAG codon has been completely repurposed. In these organisms, TAG never functions as a stop signal; it always encodes pyrrolysine. This genome-wide reassignment effectively creates a different genetic code, with 62 sense codons encoding 21 amino acids and only two remaining stop codons. The researchers have termed this alternative system the “Pyl code”.
Evidence from diverse environments
Using computational analysis, the scientists identified nine groups of archaea likely to use this code. Two were examined experimentally: , which survives in the extreme cold of Antarctic lakes, and , found in the human gut. Protein analysis confirmed that dozens of their proteins contain pyrrolysine at positions where a stop signal would normally appear, demonstrating consistent use of the Pyl code.
Why protein prediction must change
Predicting protein sequences from DNA depends on reading genes using the standard genetic code. For archaea using the Pyl code, this method would incorrectly truncate proteins at TAG codons. The study shows that scientists must instead interpret every TAG codon as encoding pyrrolysine to accurately predict protein structure and function in these organisms.
Implications for biotechnology
The discovery has practical significance beyond evolutionary biology. Researchers demonstrated that the cellular machinery required to read the Pyl code can be transferred into . Once engineered, the bacterium was able to insert pyrrolysine at specific positions in proteins. Scientists such as and suggest this capability could allow the design of proteins with new chemical properties and functional advantages.
What to note for Prelims?
- The genetic code has 64 codons, traditionally divided into 61 sense codons and 3 stop codons.
- Pyrrolysine is a rare, genetically encoded amino acid.
- Archaea form a distinct domain of life, separate from bacteria and eukaryotes.
- TAG is a stop codon in the standard genetic code.
What to note for Mains?
- How deviations from the universal genetic code inform evolutionary biology.
- Implications of alternative genetic codes for genome annotation and protein prediction.
- Potential applications of the Pyl code in synthetic biology and bioengineering.
- The role of microbial diversity and extreme environments in driving biological innovation.
