Genetic code and translation

The genetic code is the rule that turns a sequence of bases into a sequence of amino acids. With 4 bases and 20 amino acids, how many bases per amino acid? The physicist George Gamow argued: one base gives only 4 combinations, two give 16, but three give 4³ = 64, enough for all 20. So the code is a triplet: three bases, a codon, stand for one amino acid. Har Gobind Khorana, Marshall Nirenberg and Severo Ochoa did the chemistry that cracked the code.

Its features:

• 61 codons code for amino acids; 3 (UAA, UAG, UGA) code for none and act as stop signals.
• AUG has two jobs: it codes for methionine and is the start codon.
• One codon codes for only one amino acid: the code is unambiguous.
• But most amino acids have more than one codon: the code is degenerate.
• It is read in a row, three at a time, with no gaps (commaless, or contiguous).
• It is nearly universal: the same codon means the same amino acid in bacteria and in people.

A useful picture: read 'RAM HAS RED CAP' three letters at a time. Insert or delete one letter, and every word after it turns to nonsense: the reading frame shifts. This is a frameshift mutation. Inserting or deleting three letters adds or removes just one word (one amino acid), and the rest reads correctly.

tRNA is the adapter between codon and amino acid. Shaped like a clover leaf (an inverted L in three dimensions), it has an anticodon loop that pairs with a codon on the mRNA, and an end that carries the matching amino acid. There are no tRNAs for the stop codons.

Translation happens on ribosomes, which have a small and a large subunit:

• First, each amino acid is attached to its tRNA, using energy from ATP: this is charging, or aminoacylation.
• The small subunit binds the mRNA, and translation begins at the start codon AUG.
• The ribosome moves along the mRNA, codon by codon; tRNAs bring the amino acids, and peptide bonds link them into a chain. In bacteria, the bond is made by the 23S rRNA of the large subunit, so this rRNA acts as an enzyme (a ribozyme).
• At a stop codon, the finished chain is released.

The mRNA also has stretches that are not translated, before AUG and after the stop codon: the untranslated regions (UTRs), which help translation run efficiently.