Mutations — Genetics & Inheritance | IGCSE Biology

Exam Frequency Analysis

Past paper frequency (2018 to 2024)

This topic accounts for approximately 17% of your exam marks.

increasing

Very High

Increasing17%

Genetic crosses, Punnett squares, and dominant/recessive allele questions appear on almost every paper.

A mutation is a rare, random change in the sequence of bases in a DNA molecule. Mutations happen continuously in every living cell, mostly without consequence.

Three types of mutation

There are three main ways the DNA sequence can change:

Type	What happens	Effect
Substitution	One base is swapped for a different base	Only the codon containing the changed base is affected. The amino acid coded for by that codon may change, but the rest of the sequence is unaffected
Insertion	A new base is added into the sequence	Shifts every codon downstream of the insertion. Usually causes a much bigger change in the protein
Deletion	A base is removed from the sequence	Like insertion, shifts every codon downstream. Usually a major effect

Most mutations don't matter

The vast majority of mutations have no effect on the organism. They can be neutral for several reasons:

The mutation happens in a non-coding region of DNA (the bit between genes).
The new codon still codes for the same amino acid (the genetic code has redundancy: many amino acids are coded for by several different codons).
The new amino acid is so similar to the original that the protein's shape and function are unaffected.

When mutations do matter

Occasionally a mutation produces a real change in the protein, with consequences:

Harmful mutations produce a protein that does not work properly. Many genetic diseases are caused by mutations of this kind. Examples:
- Sickle cell anaemia: a single base substitution in the gene for haemoglobin changes one amino acid. The mutant haemoglobin sticks together in the wrong shape, deforming red blood cells into sickle shapes that block small blood vessels.
- Cystic fibrosis: a mutation in a gene called CFTR produces a faulty membrane protein. This causes thick sticky mucus to build up in the lungs and digestive system.
- Huntington's disease: an extra repetition of three bases in a gene called HTT produces a protein that damages brain cells in middle age.
Beneficial mutations produce a protein that works better, or gives a new function. If the new variant helps the organism survive or reproduce, it can spread through the population by natural selection (covered in topic 14).
Cancer is caused by mutations in the genes that normally control cell division. The mutated cells divide uncontrollably, forming a tumour.

What causes mutations

Mutations happen spontaneously during DNA replication, even with no external cause. Cells have repair mechanisms to fix most mistakes, but a few slip through.

Several external factors increase the rate of mutation:

Ionising radiation: gamma rays, X-rays, ultraviolet (UV) rays. Energy from the radiation breaks bonds in DNA molecules.
Chemical mutagens: certain chemicals damage DNA directly. Examples include the tar in tobacco smoke, some pesticides, and a small number of industrial chemicals.
Some viruses can insert their own DNA into the host's chromosome, disrupting genes.

People exposed to large doses of these factors over time have a higher risk of developing cancer. This is why skin protection from UV, avoiding smoking, and minimising exposure to radiation all reduce cancer risk.