In the genetic code, a stop codon is a nucleotide triplet within messenger RNA that signals
a termination of translation.
Proteins are based on polypeptides, which are unique sequences of amino acids.
Most codons in messenger RNA correspond to the addition of an amino acid to a growing
polypeptide chain, which may ultimately become a protein.
Stop codons signal the termination of this process by binding release factors, which
cause the ribosomal subunits to disassociate, releasing the amino acid chain.
While start codons need nearby sequences or initiation factors to start translation, stop
codon alone is sufficient to initiate termination.
Introduction In the standard genetic code, there are several
stop codons: in RNA:
UAG UAA
UGA
in DNA: TAG
TAA TGA
The UGA codon has recently been identified as the codon coding for Selenocysteine.
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.
The UAG codon can translate into pyrrolysine in a similar way selenocysteine is encoded.
Distribution of stop codons within the genome of an organism are non-random and can correlate
with GC-content.
For example, the E. coli K-12 genome contains 2705 TAA, 1257 TGA, and 326 TAG stop codons.
Nonsense mutations are changes in DNA sequence that 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, viruses that infect the bacteria Escherichia
coli.
Mutations in viral genes weakened their infectious ability, sometimes creating viruses that were
able to infect and grow within only certain varieties of E coli.
amber mutations were the first set of nonsense mutations to
be discovered, isolated by Richard Epstein and Charles Steinberg and named after their
friend Harris Bernstein.
Viruses with amber mutations are characterized by their ability to infect only certain strains
of bacteria, known as amber suppressors.
These bacteria carry their own mutation that allow a recovery of function in the mutant
viruses.
For example, a mutation in the tRNA that 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 that can grow in bacteria that
contain amber suppressor mutations.
Can also be placed with other viruses.
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".
opal mutations or umber mutations the third and last stop codon in the standard
genetic code was discovered soon after, corresponding to the nucleotide triplet "UGA".
Nonsense mutations that created this premature stop codon were later called opal mutations
or umber mutations.
Amber suppressors are tRNA molecules that carry a mutation that suppresses an amber
stopcodon.
It can thus read through an amber stopcodon.
The same applies for opal or ochre suppressors.
It literally means they suppress an amber/ochre or opal sequence.
Hidden stops Hidden stops are non-stop codons that would
be read as stop codons if they were frameshifted +1 or -1.
These prematurely terminate translation if the corresponding frame-shift occurs before
the hidden stop.
It is hypothesised that this decreases resource waste on nonfunctional proteins and the production
of potential cytotoxins.
Researchers at Louisiana State University propose the ambush hypothesis, that hidden
stops are selected for.
Codons that can form hidden stops are used in genomes more frequently compared to synonymous
codons that would otherwise code for the same amino acid.
Unstable rRNA in an organism correlates with a higher frequency of hidden stops.
Online software Finding stop codons in a DNA sequence and
calculate space between them See also
Genetic code Start codon
References