The Genetic code
The genetic code is a triplet code in which each codon (a set of three contiguous bases) in an mRNA specifies one amino acid. The code is degenerate: some amino acids are specified by more than one codon. The genetic code is nonoverlapping and almost universal. Specific codons are used to signify the start and end of protein synthesis.
Francis Crick and colleagues 1961 published the first strong evidence in support of a triplet code (three nucleotides per codon).
Genetic code was cracked by the combined efforts of Marshall Nirenberg, Severo Ochoa, H. Ghobind Khorana, Philip Leder, and their colleagues who worked out the meaning of all 64 triplet codons. Nirenberg and Khorana shared the 1968 Nobel Prize in Physiology or Medicine for their work on the code with Robert Holley, who determined the complete nucleotide sequence of the yeast alanine tRNA.

Properties of genetic code
The genetic code is composed of nucleotide triplets. Three nucleotides in mRNA specify one amino acid in the polypeptide product. Codon is a triplet. Out of the 64 codons, 61 codons code for 20 amino acids and 3 codons (UAA, UGA, and UAG) do not code for any amino acids. Thus, they function as initiation and termination codons.
1. The genetic code contains start and stop codons
- Specific start and stop signals for protein synthesis are contained in the code. In both eukaryotes and prokaryotes, AUG (which codes for methionine) is almost always the start codon for protein synthesis.
- GUG occasionally
- The three stop codons have been given names: UAG is amber, UGA is opal, and UAA is ochre. “Amber” was named by discoverers Richard Epstein and Charles Steinberg,
- Termination codons: UAG, UAA, and UGA. These three codons are the stop codons, also called nonsense codons or chain-terminating codons. They are used to specify the end of the translation of a polypeptide chain. Thus, when we read a particular mRNA sequence, we look for a stop codon located at a multiple of three nucleotides—in the same reading frame—from the AUG start codon to determine where the amino acid coding sequence for the polypeptide ends. This is called an open reading frame (ORF)
2. The genetic code is non-overlapping.
Each nucleotide in mRNA belongs to just one codon except in rare cases where genes overlap and a nucleotide sequence is read in two different reading frames.
3. The genetic code is comma-free.
There are no commas or other forms of punctuation within the coding regions of mRNA molecules. During translation, the codons are read consecutively.
4. The genetic code is degenerate.
The occurrence of more than one codon per amino acid is called degeneracy. Examples of degeneracy
- Leucine, serine, and arginine are each specified by six different codons.
- Met and Trp are each coded by a single codon.
- Isoleucine has three codons while the others have either two or four codons.
The degeneracy in the genetic code is of two types.
- Partial degeneracy occurs when the third base may be either of the two pyrimidines (U or C) or either of the two purines (A or G).
- In complete degeneracy, any of the four bases may be present at the third position in the codon, and the codon will still specify the same amino acid. For example, valine is encoded by GUU, GUC, GUA, and GUG
5. The genetic code is ordered
- Multiple codons for a given amino acid and codons for amino acids with similar chemical properties are closely related, usually differing by a single nucleotide.
- Leucine, isoleucine, and valine have codons that differ from each other by only one base.
- Orderedness in genetic code minimizes the effects of mutations
6. The genetic code is nearly universal
- Genetic code is the same for all living beings except in the mitochondria of mammals, yeast, and several other spp.
- UGA specifies tryptophan rather than chain termination
- AUA is a methionine codon, not an isoleucine codon
- AGA and AGG are stop codons rather than arginine codons.
7. Co-linearity
- DNA is a linear polynucleotide chain and a protein is a linear polypeptide chain.
- The sequence of amino acids in a polypeptide chain corresponds to the sequence of nucleotide bases in the gene (DNA) that codes for it.
- A change in a specific codon in DNA produces a change of amino acid in the corresponding position in the polypeptide.
- The gene and the polypeptide it codes for are said to be co-linear.
8. Translation of mRNA occurs in 5′ → 3′ direction.
61 of 64 codons code for the 20 common amino acids. For example, the codon 5′-CAU-3′ codes for histidine, whereas 5’AUG-3′ codes for methionine.
Codon-tRNA Interactions
- The accurate recognition of codons on mRNA by aminoacyl-tRNAs is essential for the correct sequence of amino acids in the polypeptide chain
- Because of the degeneracy of the genetic code, there are two possibilities:
- Multiple different tRNAs must recognize the degenerate codons
- or the anticodon of a given tRNA must be able to base-pair with degenerate codons.
- Both of these phenomena occur. Several tRNAs exist for certain amino acids, and some tRNAs recognize more than one codon.
- F. Crick proposed in 1961 that the hydrogen bonding between the bases in the anticodons of tRNAs and the codons of mRNAs follows strict base-pairing rules only for the first two bases of the codon.
- The base-pairing involving the third base of the codon is less stringent, allowing wobble at this site.
- Wobble base pairing allows several types of base pairing (other than Watson – Crick pairing) at the third codon base during the codon-anticodon interaction.
- The wobble hypothesis predicted the existence of at least two tRNAs for each amino acid with codons that exhibit complete degeneracy.
- The wobble hypothesis also predicted the occurrence of three tRNAs for the six serine codons.
- Crick’s wobble hypothesis nicely explains the relationships between tRNAs and codons given the degenerate but ordered genetic code.
References
- Principles of Genetics Sixth Edition by D. Peter Snustad and Michael J. Simmons, John Wiley & Sons, Inc.
- Genes VIII 2004 by Benjamin Lewin Published by Pearson Prentice Hall Pearson Education, Inc.
- Genetics: A Conceptual Approach by Benjamin A. Pierce, 3rd edition 2009, WH Freeman and Company