Cracking codons

Ribosome and protein synthesis

Source: © Gunilla Elam/Science Photo Library

Understanding how chemistry links RNA triplets to the properties of amino acids

The genetic code has been dubbed ‘life’s greatest secret’.1 The code relates a sequence of DNA nucleotide bases in a gene to that of amino acids in the protein that gene encodes. Each of the 20 amino acids in proteins is represented by a different triplet of the four DNA nucleotides (denoted C, G, A, T) – or more properly, of the four nucleotides (C, G, A, U) of the messenger RNA (mRNA) molecules that act as an intermediary in the translation process. There are 64 permutations of bases, so the code has some redundancy: most amino acids are represented by two or more triplets (called codons) in mRNA.

The cracking of the genetic code began in 1961 when biochemists Marshall Nirenberg and Heinrich Matthaei at the US National Institutes of Health in Maryland found the first correspondence between a particular codon (UUU) and an amino acid (phenylalanine). By mid-1965 Nirenberg’s group had decoded 54 of the 64 possible codons; the last one (UGA) was finally decrypted in 1967, proving to be one of the three codons that, rather than encoding an amino acid, tells the translation machinery of the ribosome to stop.