Single-gene mutations (substitution including missense, nonsense and splice-site; insertion and deletion causing frame-shift) and chromosome structure mutations (deletion, duplication, inversion, translocation), and their effects on proteins and phenotype.

What this dot point is asking

The SQA wants you to describe the single-gene mutations (substitution, insertion and deletion), explain their effects on the protein (missense, nonsense, splice-site and frame-shift), describe the chromosome structure mutations (deletion, duplication, inversion and translocation), and explain how these changes affect the phenotype.

Single-gene mutations

There are three basic types, and the consequences depend on how the reading frame is affected.

Substitution. One base is replaced by a different base, so only one codon changes. The effect can be:

• Missense, where the new codon codes for a different amino acid, changing one amino acid in the protein.
• Nonsense, where the new codon becomes a stop codon, ending the protein early and usually making it non-functional.
• A splice-site change, where the substitution occurs at the boundary of an intron and exon, disrupting splicing so the wrong regions are removed or kept.
• A silent change, where the new codon still codes for the same amino acid, so the protein is unchanged.

Insertion and deletion. A nucleotide is added (insertion) or removed (deletion). Because codons are read in fixed groups of three, adding or losing a base shifts the reading frame:

Chromosome structure mutations

Larger mutations change whole sections of a chromosome rather than single bases:

• Deletion - a section of the chromosome is lost, so those genes are missing.
• Duplication - a section is repeated, so those genes are present in extra copies.
• Inversion - a section breaks off, turns through 180 degrees and rejoins, reversing the order of its genes.
• Translocation - a section becomes attached to a different, non-homologous chromosome.

Because these mutations move, lose or copy many genes at once, they often have large effects on the phenotype, although duplication can be important in evolution by providing extra gene copies that may take on new functions.

Effects on phenotype

Most mutations occur in the body's cells at a low natural rate, and mutagens such as ultraviolet light, X-rays and some chemicals increase that rate. A mutation may be harmful (producing a faulty protein and a genetic disorder), neutral (no noticeable effect), or occasionally beneficial (giving an advantage). Whatever its effect, a mutation is the only source of brand-new alleles and so is the ultimate origin of all genetic variation.

Examples in context

Example 1. Sickle-cell anaemia. A single substitution mutation in the gene for haemoglobin changes one amino acid (a missense mutation), producing an abnormal haemoglobin that distorts red blood cells. This shows how even a one-base change can alter a protein and the phenotype.

Example 2. Cancer-causing mutations. Mutagens such as ultraviolet light cause mutations in genes that control the cell cycle. If a mutation removes the brakes on cell division, the cell may divide uncontrollably and form a tumour, linking mutation directly to the loss of cell-cycle control.

Try this

Q1. Name the type of single-gene mutation that adds an extra nucleotide to the sequence. [1 mark]

• Cue. Insertion.

Q2. Explain why a frame-shift mutation usually has a greater effect than a substitution. [1 mark]

• Cue. A frame-shift changes every codon after the mutation, while a substitution changes at most one codon.