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.

Codon	Amino acid
UUU	phenylalanine
UUC	phenylalanine
AUG	methionine (START)
GGU	glycine
GGC	glycine
GGA	glycine
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