The Genetic Code

The rulebook that maps every three-letter codon of nucleotides onto an amino acid or a stop signal, and the experiments that cracked it.

Definition

The genetic code is the correspondence between the 64 nucleotide triplets (codons) of messenger RNA and the 20 standard amino acids plus translational stop signals, read in a fixed frame to specify a protein's sequence.

Scope

This topic covers the structure and properties of the genetic code: its triplet, non-overlapping, comma-free reading; codon–amino-acid assignments including start and stop codons; degeneracy and wobble; the reading frame; and the near-universality of the code with its known exceptions. It treats the code itself; the machinery that reads it is covered in companion topics on the ribosome and tRNA.

Core questions

• How was it established that the code is read in non-overlapping triplets?
• How were individual codons assigned to amino acids?
• Why does the code have more codons than amino acids, and what is wobble?
• How universal is the code, and what exceptions exist?

Key theories

Triplet, non-overlapping code

Genetic information is read in consecutive groups of three nucleotides without overlap, so a defined reading frame determines which codons are read; frameshifts scramble the message downstream.

Degeneracy and wobble

Most amino acids are encoded by several synonymous codons that usually share their first two positions, and flexible pairing at the third codon position (wobble) lets a single tRNA read more than one codon.

Mechanisms

The code was decoded by translating synthetic RNAs in cell-free systems: a poly(U) template directed synthesis of polyphenylalanine, assigning UUU to phenylalanine, and systematic use of defined polymers and triplets assigned the remaining codons. The 64 codons include 61 sense codons specifying amino acids and 3 stop codons; a single start codon also sets the reading frame. Degeneracy concentrates synonymous codons so that third-position changes are often silent, and wobble pairing economises on the number of tRNAs needed.

Clinical relevance

Because reading frame and codon identity determine protein sequence, point mutations, nonsense mutations, and frameshifts have predictable consequences for protein products and underlie many genetic conditions; presented as significance, not clinical guidance.

History

Nirenberg and Matthaei's 1961 poly(U) experiment made the first codon assignment; Khorana's defined polymers, Holley's tRNA sequencing, and Crick's adaptor and wobble proposals completed the code, recognised by the 1968 Nobel Prize in Physiology or Medicine.

Key figures

• Marshall Nirenberg
• Har Gobind Khorana
• Francis Crick
• Robert Holley

Seminal works

• nirenberg1961
• watson2013

Frequently asked questions

How many codons are there and what do they encode?

There are 64 codons: 61 specify amino acids and 3 are stop signals; one codon also serves as the usual start, setting the reading frame.

What is wobble?

Flexible base pairing at the third codon position that lets one transfer RNA recognise several synonymous codons, reducing the number of tRNAs a cell needs.