The Genetic Code: Three Letters at a Time

Why three?

The message is written in only four letters — A, U, G, C — but proteins are built from about twenty different amino acids. Four letters read one at a time could only name four amino acids; read two at a time, only sixteen. You need at least three letters per word to get past twenty. And indeed, the cell reads the message in triplets. Each three-letter word is a codon, and the full lookup table from codon to amino acid is the genetic code.

Three letters from four options give 4 × 4 × 4 = 64 possible codons — more than enough for twenty amino acids. The extras are not wasted: most amino acids are spelled by more than one codon, a redundancy that makes the code robust against small errors. We call the code degenerate for this reason, but never ambiguous: each codon means exactly one thing.

Where the words begin: the reading frame

There are no spaces between codons, so where you begin counting decides every word that follows. That starting point and the triplet grouping it sets up are called the reading frame. Slide your starting point over by one letter and every codon downstream changes — the sentence becomes nonsense.

So the cell does not start counting from a random spot. It looks for a specific signal — the start codon, the triplet AUG — and begins the reading frame there. AUG does triple duty: it says 'start here,' it sets the frame, and it also codes for the amino acid methionine, the first one in almost every new protein.

Reading to the end

Reading continues codon by codon, adding one amino acid for each, until the cell hits one of three special triplets — UAA, UAG, or UGA — that name no amino acid at all. These are the stop codons. They are full stops: when one appears in frame, the protein is finished and released. Start codon to stop codon, the reading frame defines exactly which stretch of message becomes a protein.

READING A MESSAGE IN FRAME

  mRNA:  ...C  AUG  GCA  UUU  GGC  UAA  C...
              └─┬─┘ └─┬─┘ └─┬─┘ └─┬─┘ └─┬─┘
  codon:      AUG   GCA   UUU   GGC   UAA
  meaning:   START  Ala   Phe   Gly   STOP
             (Met)

  Protein built: Met - Ala - Phe - Gly   (then released at STOP)

  Now shift the frame by ONE letter to the right:
  ...CA  UGG  CAU  UUG  GCU  AAC...
        Trp   His   Leu   Ala   Asn   ← a completely different protein!

  Same letters, different starting point = different message.