stop codon

In the genetic code, a stop codon (or termination codon) is a nucleotide triplet within messenger RNA that signals a termination of translation.^[1] Proteins are unique sequences of amino acids, and most codons in messenger RNA correspond to the addition of an amino acid to a growing protein chain — stop codons signal the termination of this process, releasing the amino acid chain. In the standard genetic code, there are three stop codons: UAG (in RNA) / TAG (in DNA) ("amber"), UAA / TAA ("ochre"), and UGA / TGA ("opal" or "umber"); several variations to this most common set are known. The UGA codon has recently been identified as the codon coding for Selenocysteine (Sec) this amino acid is found in 25 selenoproteins where it is located in the active site of the protein. Transcription of this codon is enabled by proximity of the SECIS element (SElenoCysteine Incorporation Sequence).^[2] Nonsense mutations are changes in DNA sequence which introduce a premature stop codon, causing any resulting protein to be abnormally shortened. This often causes a loss of function in the protein as critical parts of the amino acid chain are no longer created. Because of this terminology, stop codons have also been referred to as nonsense codons.

Amber, ochre, and opal nomenclature

Stop codons were historically given many different names as they each corresponded to a distinct class of mutants that all behaved in a similar manner. These mutants were first isolated within bacteriophages (T4 and lambda), viruses that infect the bacteria Escherichia coli. Mutations in viral genes weakened their infectious ability, sometimes creating viruses that were only able to infect and grow within certain varieties of E coli.

Amber mutations were the first set of nonsense mutations to be discovered, isolated by graduate student Harris Bernstein in experiments designed to resolve a debate between Richard Epstein and Charles Steinberg. Bernstein (whose last name means "amber" in German) had been offered the reward of having any discovered mutants named after himself.^[3]

Viruses with amber mutations are characterized by their ability to only infect certain strains of bacteria, known as amber suppressors. These bacteria carry their own mutation which allow a recovery of function in the mutant viruses. For example, a mutation in the tRNA which recognizes the amber stop codon allows translation to "read through" the codon and produce full length protein, thereby recovering the normal form of the protein and "suppressing" the amber mutation. Thus, amber mutants are an entire class of virus mutants which can grow in bacteria that contain amber suppressor mutations.

The ochre mutation was the second stop codon mutation to be discovered. Given a color name to match the name of amber mutants, ochre mutant viruses had a similar property in that they recovered infectious ability within certain suppressor strains of bacteria. The set of ochre suppressors was distinct from amber suppressors, so ochre mutants were inferred to correspond to a different nucleotide triplet. Through a series of mutation experiments comparing these mutants with each other and other known amino acid codons, Sydney Brenner concluded that the amber and ochre mutations corresponded to the nucleotide triplets "UAG" and "UAA".^[4]

The third and last stop codon in the standard genetic code was discovered soon after, corresponding to the nucleotide triplet "UGA".^[5] Nonsense mutations that created this premature stop codon were later called opal mutations or umber mutations.

References