From RNA to protein: translation

The genetic code

Messenger RNA is written in a four-letter alphabet; proteins in a twenty-letter one. The genetic code is the conversion table between them.

Why groups of three

The argument is purely combinatorial, and it was made before any experiment:

if 1 base coded 1 amino acid  ->  4 possibilities     insufficient
if 2 bases coded             ->  4² = 16             still insufficient
if 3 bases code              ->  4³ = 64             sufficient (20 needed)

The code is therefore a triplet code: each group of three bases, a codon, designates an amino acid.

A redundant code

64 codons for 20 amino acids: several codons designate the same amino acid.

   UUU  ->  phenylalanine         GGU  ->  glycine
   UUC  ->  phenylalanine         GGC  ->  glycine
                                  GGA  ->  glycine
   AUG  ->  methionine (START)    GGG  ->  glycine
   UAA, UAG, UGA  ->  STOP        (no amino acid)

This redundancy is not waste: it cushions mutations. If the third base of a codon changes, the amino acid often stays the same — the four glycine codons differ only in their last letter. The code is built so that the most frequent errors are the least damaging.

Careful not to reverse it: the code is redundant but unambiguous. A given codon always codes the same amino acid; the converse is what fails.

Punctuation

AUG        START codon: marks the beginning, and codes methionine
UAA, UAG, UGA   STOP codons: mark the end, code no amino acid

The AUG codon also sets the reading frame: it is from there that the RNA is cut into triplets. The same sequence read one base out of step gives an entirely different protein.

   AUG CCU GAA UAC ...        correct frame
   A UGC CUG AAU AC...        shifted by one base: unreadable message

A near-universal code

This is one of the strongest arguments for a common origin of life: the same genetic code works in a bacterium, a yeast, an oak and a human. The codon GGU means glycine everywhere.

This universality has a major practical consequence: a human gene can be inserted into a bacterium, and it will make the corresponding human protein. That is how insulin has been produced since 1982 — before which it was extracted from pig pancreases.

A few rare exceptions exist, notably in mitochondria, where one or two codons have a different meaning. They confirm the rule more than they weaken it.

Summary