The genetic code and mutations

Four letters, twenty amino acids

A protein is made of 20 kinds of amino acids. DNA has only four kinds of bases. How can four letters spell twenty words?

George Gamow, a physicist, worked it out. A code of single bases would give only 4 words. A code of pairs would give $4^2 = 16$, which is still too few. A code of triplets gives $4^3 = 64$, which is more than enough. A group of three bases that stands for one amino acid is a codon.

Then came the experiments that read the code.

• Har Gobind Khorana found a chemical way to make RNA with a known order of bases.
• Marshall Nirenberg made a cell-free system that could build protein from an RNA. The first codon that he read was UUU, which stands for phenylalanine.
• Severo Ochoa found an enzyme that makes RNA with chosen bases, without any template.

With these tools, all 64 codons were read. Codons are written for the mRNA, from the 5′ end to the 3′ end.

The code

The table gives the amino acid for each codon. Find the first two bases in the left column, and the third base in the top row.

You do not have to learn the table. But you must know its main features.

1. The codon is a triplet.
2. Of the 64 codons, 61 code for amino acids. Three, UAA, UAG and UGA, do not code for any amino acid. They are the stop codons.
3. AUG codes for methionine, and it is also the start codon. It has two jobs.
4. Many amino acids have more than one codon. The code is degenerate. Leucine, serine and arginine have six codons each, and methionine and tryptophan have only one.
5. The code is unambiguous and specific. One codon codes for one amino acid only.
6. The codons are read one after another, with no gaps or punctuation, and none of them overlaps with the next.
7. The code is nearly universal. UUU stands for phenylalanine in a bacterium and in a human. There are a few exceptions, such as in mitochondria. In human mitochondria, UGA codes for tryptophan.

This part is not in the NEET syllabus, but A-Level and IB ask it. The first two bases of a codon often decide the amino acid, and the third base is less important. This is the idea of the wobble. It is why a change in the third base is often silent.

Mutations and the code

A mutation is a change in the DNA. A point mutation changes one base. Its effect depends on the codon that it lands in.

The best-known point mutation is in sickle-cell anaemia. The sixth codon of the gene for the beta chain of haemoglobin is GAG. In the mutant it is GUG. The amino acid glutamic acid (Glu) is replaced by valine (Val). One base, one amino acid, and the haemoglobin changes.

Now think of an insertion or a deletion of bases. The mRNA is read three bases at a time. If one or two bases are added or lost, the reading of every codon after that point is shifted. This is a frameshift mutation, and it usually ruins the protein. If three bases (or a multiple of three) are added or lost, the reading frame is kept. The protein only gains or loses one or more amino acids.

You should find that a change of 1 or 2 bases spoils the frame from that codon to the end, and a change of 3 bases does not.

Try it in Python

The program builds the genetic code in a table, and counts its codons. In the program, M is methionine, W is tryptophan, L is leucine, S is serine and R is arginine.

The next program changes one base at a time in a codon and says what each change does. It uses the codon UUU for phenylalanine.

Practise with new numbers

Common mistakes

• Saying that the stop codons code for an amino acid. UAA, UAG and UGA have no amino acid.
• Saying that the code is not degenerate. An amino acid may have up to six codons, and each codon has one amino acid.
• Saying that one codon can code for two amino acids. The code is unambiguous.
• Saying that a deletion of three bases spoils the frame. It keeps the frame.
• Writing T in an mRNA codon. An mRNA has U.

Remember these

• 64 codons. 61 for amino acids and 3 stop codons (UAA, UAG, UGA). AUG is Met and the start codon.
• The code is triplet, degenerate, unambiguous, read without gaps and nearly universal.
• A point mutation can be silent, missense or nonsense. Sickle-cell: GAG to GUG, Glu to Val.
• Insertion or deletion of 1 or 2 bases is a frameshift. 3 bases keep the frame.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. Why must a codon have three bases?

2. Which codons are the stop codons, and what do they code for?

3. What does it mean that the genetic code is degenerate?

4. What is the change in the DNA that causes sickle-cell anaemia, and what does it do to the protein?

5. Why does the deletion of one base do more harm than the deletion of three?

References

• NCERT (2023). Biology, Textbook for Class XII, chapter 5, Molecular Basis of Inheritance.
• Clark M. A. et al. (2018). Biology 2e, OpenStax, chapter 15, section 15.1, The Genetic Code.
• Crick F. H. C. et al. (1961). General nature of the genetic code for proteins. Nature, 192, 1227 to 1232.