The blueprint for all life on Earth is encoded in deoxyribonucleic acid, or DNA, which contains the instructions for building and maintaining an organism. This information is first copied into messenger RNA (mRNA) before being translated into proteins, the molecular machines that perform nearly all cellular functions. The “genetic code” refers to the set of rules that governs how the sequence of information in the mRNA is read to assemble the correct sequence of amino acids. The entire system is built upon a fundamental set of 64 possible codes that are overwhelmingly conserved across all known organisms.
The Core Structure Codons and Amino Acids
The genetic code is based on a four-letter alphabet derived from the nitrogenous bases—Adenine (A), Guanine (G), Cytosine (C), and Uracil (U) in RNA. These four bases are read in groups of three, known as codons, which function like molecular words. Because there are four possible bases and each codon consists of three positions, the total number of unique combinations results in 64 possible codons.
These 64 codons provide the instructions for incorporating the 20 standard amino acids used by life. Of the 64 total codons, 61 are classified as “sense” codons, meaning they specify one of the 20 amino acids. The remaining three codons—UAA, UAG, and UGA—act as “stop” signals, indicating the end of a protein chain. The codon AUG codes for Methionine and also acts as the “start” signal to begin protein synthesis.
A significant feature of this system is its redundancy, also called degeneracy, where multiple different codons can specify the same amino acid. For instance, Leucine is specified by six different codons, while Methionine and Tryptophan are specified by only one each. This redundancy helps buffer the organism against random mutations, as a change in the third position often still results in the incorporation of the correct amino acid.
The Principle of Near Universality
The standard genetic code is considered universal because the meaning of the 64 codons is largely consistent across all three domains of life: Bacteria, Archaea, and Eukaryota. This means that the codon sequence UUU specifies the amino acid Phenylalanine in any organism. The shared nature of this code is one of the strongest pieces of evidence supporting the theory that all life on Earth shares a single common ancestor.
This universality is striking because the same set of codon-amino acid assignments is maintained across billions of years of evolution. The preservation of this system suggests that any change to the code would likely be lethal, as it would alter the amino acid sequence of thousands of proteins simultaneously. The standard code is stable and serves as the baseline for genetic information transfer in the vast majority of organisms.
Known Variations and Exceptions
While the standard code dominates, specific organisms and cellular compartments exhibit minor deviations, confirming the code is “near universal.” The most common examples are found within the small, circular genomes of mitochondria, the energy-producing organelles in eukaryotic cells. For instance, in mammalian mitochondria, the codons AGA and AGG, which code for Arginine in the nuclear code, are re-assigned as stop codons.
Furthermore, the codon UGA, a stop signal in the standard code, is sometimes re-assigned to code for the amino acid Tryptophan in mammalian and Drosophila mitochondria. Similar re-assignments of one or two codons have been observed in the nuclear codes of certain single-celled organisms, such as some protists and specific strains of bacteria. These localized variations typically involve a change in function for one of the three stop codons.
A few organisms also incorporate non-standard amino acids into their proteins by re-purposing a stop codon. Selenocysteine, the 21st amino acid, is incorporated when the UGA stop codon is encountered alongside a specific mRNA structure called a SECIS element. Similarly, the 22nd amino acid, Pyrrolysine, is incorporated by certain archaea and bacteria in response to the UAG stop codon. These exceptions demonstrate that the core 64-codon system can evolve under specific conditions.