5.4 - Mutations

What a mutation is and how it changes the protein

• A mutation is a random change to the sequence of bases in DNA.
• Mutations happen continuously and arise spontaneously - for example when DNA isn't copied perfectly as a cell prepares to divide.
• A mutation produces a genetic variant - a different form of the gene, also called a new allele - and can sometimes be passed from parent to offspring.

How a mutation changes the protein

• The order of bases in a gene sets the order of amino acids in the protein it codes for, read three bases at a time - each triplet codes for one amino acid.
• A mutation that changes the base sequence can change which amino acids are joined, and so change the protein that's built.
• A protein folds into a particular shape that depends on its amino-acid sequence, and that shape lets it do its job.
• So changing the amino acids can change the shape, and so change how well the protein works - its activity might increase, decrease, or stop altogether.

Effect on the phenotype ranges from none to large

A mutation often changes nothing, because:

• The changed triplet may still code for the same amino acid.
• The change to the protein may be too small to alter its shape and function.
• The mutation may fall in a part of the DNA that does not do an important job, or sit in a recessive allele masked by a dominant one.

Other outcomes:

• Small effect - Alters a characteristic only slightly.
• Large effect - Occurs when a key protein is badly disrupted or not made at all.

The two kinds of protein where this matters most

1. Enzymes - Have an active site with a very specific shape that the substrate fits into. If a mutation changes the active site's shape, the substrate may no longer bind, so the enzyme can't speed up its reaction. A mutation can even stop the enzyme being produced at all.
2. Structural proteins (e.g. collagen) - Depend on their shape to give strength and support. If a mutation changes that shape, the protein can lose its strength and become much less useful for holding tissues together.

Mutations in coding and non-coding DNA

• Genes are sequences of bases that code for proteins.
• Non-coding DNA is DNA that does not code for any protein.
• Mutations aren't confined to genes - they can happen in either coding or non-coding DNA.

Effect of the mutation depends on where it is

• Coding DNA - A mutation changes the protein the gene makes, so it can change how the protein works.
• Non-coding DNA - A mutation doesn't change a protein directly. Instead, some non-coding DNA controls the expression of nearby genes, so a mutation there can:
  • Change whether a gene is switched on or off, and how strongly it's expressed
  • Change how much of a protein is made, or stop that protein being made at all

A mutation in non-coding DNA can therefore still affect the phenotype, even though it doesn't lie within a gene.