Higher Biology | Key Area 1.6: Mutations

Mutation

A change in the genome (DNA), that can result in either an altered protein or no protein being synthesised and expressed.

Single gene mutation

A mutation that involves the alteration of a DNA nucleotide sequence, and affects a few bases as a result of the:

- Substitution of a nucleotide with another (can also be one or more bases in the sequence replaced by the same number of bases), eg. ATTCAGC → ATTCATC

- Insertion of one or more extra nucleotides into a DNA sequence, eg. ATTCAGC → ATTCGTAGC

- Deletion of one or more extra nucleotides from a DNA sequence, eg. ATTCAGC → ATTAGC

Point mutation

A one-codon change caused by a nucleotide substitution.

Substitution mutations affect one amino acid in a primary structure. What are the three resulting types of mutation caused by substitutions?

- Missense mutation

- Nonsense mutation

- Splice-site mutation

Missense mutation

A type of substitution mutation, where a changed codon results in the production of a different amino acid.

What types of proteins can be produced by missense mutations?

- If the changed amino acid has different chemical properties from the one coded for by the original sequence, the protein produced will also have different chemical properties and/or have a changed shape. It will not carry out its intended function and so is a non-functional protein.

- If the changed amino acid has similar chemical properties to the one coded for by the original sequence, the protein’s folded shape may be unaffected and function similarly to the original protein.

Name examples of disorders caused by missense mutations:

Sickle cell disease; phenylketonuria (PKU)

Nonsense mutation

A type of substitution mutation, where a codon is changed from coding for an amino acid to representing a premature stop codon, resulting in a shorter protein as translation ends early.

What types of proteins can be produced by nonsense mutations?

Shorter proteins are generally non-functional, or have functions that are greatly affected.

Name examples of disorders caused by nonsense mutations:

Duchenne muscular dystrophy (DMD)

Splice-site mutation

A type of substitution mutation, where substitutions affect the boundaries between introns and exons (ie. the splice sites) and result in introns being retained, or exons being excluded from the mature mRNA transcript.

What types of proteins can be produced by splice-site mutations?

Very different proteins are produced since mutations can prevent splicing at affected sites. These are generally non-functional.

Name examples of disorders caused by splice-site mutations:

Beta thalassemia; thrombotic thrombocytopenic purpura (TTP)

Frameshift mutation

- A mutation caused by the insertion or deletion of DNA nucleotides, where all codons (and so amino acids) after the mutation are changed.

- When codons are read at the ribosome, the codon reading frame is shifted by one codon.

What type of proteins can be produced by frameshift mutations?

Since completely different amino acids are coded for after the mutation, resulting proteins are significantly altered and so are generally non-functional.

Name examples of disorders caused by frameshift mutations:

Cystic fibrosis (deletion); Tay-Sachs disease (insertion)

Chromosome mutations

Mutations that affect whole chromosomes, involving a change in the structure or number of chromosomes.

What are chromosome structure mutations caused by?

They result from errors in cell division.

What do chromosome structure mutations make a chromosome?

Substantial changes to chromosome structure often makes them lethal.

What are the four types of chromosome structure mutation?

- Deletion

- Inversion

- Duplication

- Translocation

Deletion chromosome mutation

Where a section of chromosome is removed, resulting in a shorter chromosome which lacks certain genes.

eg. AB•CDEFGH → AB•CDGH

Inversion chromosome mutation

Where a section of chromosome breaks in two places and a set of genes rotates through 180° (ie. reversed), causing a complicated loop to be formed at gamete formation, often resulting in non-viable gametes.

eg. AB•CDEFGH → AB•CDGFEH

Translocation chromosome mutation

Where a section of chromosome is added to a chromosome not its homologous partner, causing problems during gamete formation, often resulting in non-viable gametes.

Non-reciprocal translocation

A one-way transfer of genes, where a section of chromosome breaks in only one chromosome and is transferred to a chromosome not its homologous partner.

eg. Chromosome 1: AB•CDEFGH & Chromosome 2: STUV•WYZ → Chromosome 1: AB•CDEFGHST & Chromosome 2: UV•WYZ

Reciprocal translocation

An exchange of genes, where a section of chromosome breaks in two chromosomes not homologous partners, and swapped.

eg. Chromosome 1: AB•CDEFGH & Chromosome 2: STUV•WYZ → Chromosome 1: AB•CDEST & Chromosome 2: FGHUV•WYZ

Duplication chromosome mutation

Where a section of chromosome is added from its homologous partner, resulting in a duplicated set of genes from the matching chromosome.

eg. AB•CDEFGH → AB•CDECDEFGH

Duplication of chromosomes may have an advantage or disadvantage:

Some duplications can be highly detrimental, whilst others can be important in evolution.

What is the importance of mutation and gene duplication in evolution?

- Duplication allows potential beneficial mutations to occur in one of the copies of the gene (DNA), whilst the original gene can still be expressed to produce its protein.

- The duplicated gene accumulates further mutations without selection pressure by altering the original gene’s function, and may produce another protein/characteristic that gives the organism a selective advantage without negative consequence.

- Duplicated genes can confer an advantage with numerous mutations over time (with new DNA sequences) since they facilitate the creation of new genes by giving rise to related genes with specialised functions.