Mutation: from a changed base to a changed protein

Where does variation come from?

Children of the same parents are not alike. Part of the reason is recombination: independent assortment, crossing over and the chance meeting of gametes. The other part is mutation, a change in the DNA. Recombination mixes the alleles that already exist. Mutation makes new alleles.

A mutation is a sudden, heritable change in the DNA. It can change the genotype and so the phenotype.

• A change in a body cell (a somatic mutation) is not passed to children. It may lead to a cancer in that person.
• A change in a cell that forms gametes (a germ line mutation) can be passed to the next generation.

Agents that cause mutations are mutagens. They are physical agents, such as ultraviolet light, X rays and gamma rays, and many chemicals. A mutation can also arise by itself during the copying of DNA.

Point mutations

A point mutation is a change of one base pair. The commonest kind is a substitution: one base takes the place of another. The effect is read from the genetic code, which you meet fully in the next chapter. A codon is a group of three bases of the mRNA, and each codon stands for one amino acid or for a stop signal.

Three results are possible.

• Silent: the new codon stands for the same amino acid. The protein does not change. This is possible because most amino acids have more than one codon.
• Missense: the new codon stands for a different amino acid. The protein has one amino acid changed.
• Nonsense: the new codon is a stop codon. The protein is cut short.

A famous missense mutation is in the gene of beta-globin, a part of haemoglobin. The codon GAG (glutamic acid) becomes GUG (valine) at the sixth position. This single change causes sickle-cell anaemia, which you meet in the next lesson. The example is in NCERT. The NTA syllabus does not name the disease, but A-Level and IB ask about it.

Frameshift mutations

The code is read in groups of three bases without a gap. If one or two bases are inserted or deleted, every group after the change is read in a new way. This is a frameshift mutation. It nearly always ruins the protein from that point on. If three bases (or a multiple of three) are inserted or deleted, the frame is kept. The protein gains or loses a whole amino acid, and the rest is read as before.

You should see that a change of 1, 2, 4 or 5 bases ruins the frame, and a change of 3 or 6 keeps it.

Chromosomal mutations

A mutation can also change the structure or the number of whole chromosomes. These are chromosomal aberrations.

• Deletion: a piece of the chromosome is lost.
• Duplication: a piece is present twice.
• Inversion: a piece is turned round and put back.
• Translocation: pieces are exchanged between two chromosomes that are not a pair.
• Aneuploidy: one chromosome, or a few, is gained or lost. It happens when chromosomes fail to separate, which is called non-disjunction. The next lesson uses it for Down syndrome.
• Polyploidy: whole sets of chromosomes are added, so a cell has 3n or 4n. It happens when cytokinesis fails after the chromosomes have separated. It is often seen in plants, and it is rare in animals.

Chromosomal aberrations are commonly seen in cancer cells.

Try it in Python

The program lists every single-base change of the codon GAG and sorts the changes. A second program shows how a deletion or an insertion shifts the frame, with a sentence of three-letter words.

Practise with new numbers

Common mistakes

• Saying that every point mutation changes the protein. A silent mutation does not, because the code has more than one codon for most amino acids.
• Thinking that a deletion of three bases is a frameshift. Three bases are one codon, so the frame is kept.
• Mixing up polyploidy and aneuploidy. Polyploidy adds whole sets. Aneuploidy adds or removes single chromosomes.
• Saying that all mutations are harmful. Many are silent, and a few help the organism. Mutations are the source of variation for evolution.

Remember these

• Mutation: a sudden change in DNA. Mutagens include ultraviolet light, X rays and chemicals.
• A substitution can be silent, missense or nonsense. A deletion or insertion of one or two bases is a frameshift.
• Chromosomal aberrations: deletion, duplication, inversion and translocation.
• Aneuploidy comes from non-disjunction. Polyploidy is a gain of whole sets.

Check yourself

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

1. In an mRNA, the codon CAU for histidine changes to CAC, which also stands for histidine. What kind of mutation is it?

2. A sequence of 24 bases, which is 8 codons, has 3 bases deleted from its middle. How many codons does it have now, and is the reading frame kept?

3. Name the chromosomal change in each case: (a) a piece is turned round; (b) a piece is lost; (c) pieces are swapped between two chromosomes that are not a pair.

4. Why can a mutation in a skin cell not be passed to a child?

5. What is the difference between aneuploidy and polyploidy?

References

• NCERT (2023). Biology, Textbook for Class XII, chapter 4, sections on mutation and chromosomal disorders.
• Clark M. A., Douglas M. and Choi J. (2018). Biology 2e, OpenStax, chapter 13.2 and chapter 15.