Topic 6.7 Notes – Mutations

1. What a Mutation Is and Why It Matters

A mutation is a permanent change in the DNA nucleotide sequence.

Because information flows
DNA → RNA → Protein,
a change in DNA can lead to:

• A different amino acid sequence
• A different amount of protein (if regulation is affected)
• A protein with altered structure and function
• A change in phenotype

Think in a chain:

Genotype change → gene product change → phenotype change

The effect depends on:

• Where the mutation occurs (coding vs regulatory vs noncoding)
• How it alters transcription or translation
• The environment

Mutations can be:

• Beneficial
• Detrimental
• Neutral

Same mutation, different environment, different outcome. That idea shows up often in FRQs.

Examples you should recognize:

• CFTR mutation → disrupted ion transport → cystic fibrosis.
• MC1R mutation in pocket mice → darker fur → camouflage advantage on dark lava rock.

You do not need to memorize specific diseases beyond examples like these, but you must explain the mechanism: altered gene → altered protein → altered trait.

2. Types of Gene Mutations

Point Mutations (Substitutions)

One nucleotide is replaced with another.

They can cause:

• Missense → different amino acid
• Nonsense → premature stop codon → shortened protein
• Silent → same amino acid (genetic code redundancy)

Silent does not change the amino acid sequence, but it can sometimes affect mRNA stability or expression level.

Nonsense mutations often cause loss of function because the protein is truncated.

Insertions and Deletions

Nucleotides are added or removed.

If the number added/removed is not a multiple of 3, you get a frameshift mutation.

A frameshift mutation occurs when a nucleotide is inserted or deleted early in a sequence, shifting the grouping of codons so that all downstream codons are read incorrectly, often leading to a premature stop codon.

A frameshift:

• Shifts the reading frame
• Changes all downstream amino acids
• Often creates a premature stop
• Usually produces a nonfunctional protein

Quick comparison:

Mutations by Functional Effect

Regardless of type:

• Loss-of-function → reduced or no protein activity
• Gain-of-function → increased or new activity
• Neutral mutation → no measurable phenotype change

Environment determines whether a mutation is helpful or harmful. The classic example is sickle cell. The mutation changes hemoglobin structure. In malaria regions, heterozygotes have increased survival. Outside those regions, the mutation is mostly harmful.

That environmental dependence is a favorite testing angle.

3. Changes in Chromosome Number and Structure

Mutations are not limited to single genes.

Changes in Chromosome Number

Usually caused by nondisjunction during meiosis or mitosis. In the diagram below, notice how chromosomes fail to separate properly in meiosis I versus meiosis II and how that changes the types of gametes produced.

Nondisjunction in meiosis I vs. meiosis II

If nondisjunction happens in meiosis I, all four gametes are abnormal, either n + 1 or n − 1. If it happens in meiosis II, two gametes are normal (n) and two are abnormal.

Results include:

• Aneuploidy → extra or missing chromosome
• Polyploidy → extra full sets of chromosomes

Effects:

• In animals, often developmental limitations
• In plants, polyploidy can increase vigor
• Triploidy often causes sterility

The key concept is gene dosage. More copies of a chromosome mean more copies of genes, which changes protein amounts.

Changes in Chromosome Structure

Structural rearrangements include:

• Deletion → segment lost
• Duplication → segment repeated
• Inversion → segment reversed
• Translocation → segment moved to another chromosome

These can:

• Disrupt genes
• Alter regulation
• Create fusion proteins (common in some cancers)

You are not expected to memorize specific syndromes. Focus on mechanism.

4. Where Mutations Come From

Mutations arise randomly due to:

Internal causes

• DNA replication errors
• Failure of DNA repair

External mutagens

• UV radiation
• X-rays
• Reactive chemicals

Important:
Mutations occur randomly with respect to fitness. Natural selection does not cause mutations. It filters them after they happen.

5. Mutations and Natural Selection

Mutations create genetic variation, the raw material for evolution.

If a mutation:

• Increases survival or reproduction → frequency increases
• Decreases fitness → selected against
• Has no effect → may persist by genetic drift

Horizontal Gene Transfer in Prokaryotes

Increases variation without reproduction:

• Transformation → uptake of free DNA
• Transduction → viral DNA transfer
• Conjugation → plasmid transfer via pilus
• Transposition → DNA segments move within genome

These mechanisms spread traits like antibiotic resistance rapidly.

Viral Recombination

If related viruses infect the same cell, their genomes can mix, forming new viral strains.

Across life, variation-increasing processes are conserved:

• All organisms experience mutations
• Prokaryotes use horizontal gene transfer
• Eukaryotes use meiosis and crossing over

Populations survive change because heritable variation exists first. Selection acts second.