Student Reader

Genetic code

Features of the genetic code
No OverlapThe codons do not overlap.
ContinutyThere are no gaps in the reading frame.
TripletThe genetic code is encoded by three-nucleotide codons.
DegenerateThere are more codons than amino acids.
Degenerate amino acids are encoded by as many as six different codons.
Other amino acids are not degenerate, and are encoded by just one codon.

Each of the 20 amino acids are specified by one or more RNA codons, which are three-nucleotide (triplet) sequences. There are also three stop codons (UGA, UAG and UAA) that signal to stop translation as well as two start codons (ATG and AUG) that signal to start translation. An open reading frame (ORF) is the nucleotide sequence between a start codon and a stop codon. Depending on where one starts reading the sequence, a nucleotide can have as many as three different reading frames; except for the ORF, these reading frames often have many stop codons. The codons are almost all universal codons and are consistent in all living organisms on Earth, except for a few unusual codons in certain species (usually a stop codon converted to encode an amino acid).

Why does a codon have three letters?
2 lettersThere would only be 16 (42) codons. Not enough for the 20 amino acids.
3 lettersThere would only be 64 (43) codons. More than enough for the 20 amino acids.
4 lettersThere would only be 256 (45) codons. Too many for the 20 amino acids.

Breaking the genetic code

Francis Crick first proposed that the genetic code consisted of triplets, and his theory was confirmed by 1968 Nobel-winning work by Marshall Nirenberg and his colleagues in 1961-1964. The genetic code was resolved by the experiment shown below.

Trinucleotide Experiment
TranslationThere were 64 tubes, all of which contained a single type of radioactively labeled amino acid (tryptophan, lysine, etc). Each tube contained a different trinucleotide (UUU, AUG, etc). An E. coli extract of translational machinery was then added to each tube. This experiment was repeated twenty times, once for each amino acid.
FiltrationEach reaction was then filtered so that only charged ribosomes remained. An amino acid can only bind to the tRNA if it is encoded for, and the tRNA can only bind the ribosome when bound to an amino acid. All 20 amino acid naturally occurred in the E. coli cell extract, but the radioactively labeled ribosomes imparted a charge to the tRNA and, thus, the ribosome.
ResultsPerforming trinucleotide experiments for each of the 64 possible trinucleotide codons, the meaning of each codon was unambiguously resolved. 61 codons were found to encode the 20 amino acids, with 3 three codons (UGA, UAG & UAA) encoding no amino acid and thus signaling to stop translation; the start codons, identified later, double to encode methionine.
Genetic codeComments