(a) types of gene mutations and their possible effects on protein production and function

Types of mutations: Substitution

• One or more bases are swapped for another • Example: ATGCCT → ATTCCT (G replaced with T) • Affects one codon so may change one amino acid

Types of mutations: Deletion

• One or more bases are removed • Example: ATGCCT → ATCT (GC deleted) • Can cause frameshift if not a multiple of 3

Types of mutations: Insertion

• One or more bases are added • Example: ATGCCT → ATGACCT (A inserted) • Often causes a frameshift

How base order affects proteins

• DNA base order determines amino acid sequence • A mutation can alter the primary structure • This can change the final 3D tertiary structure • Active sites may not form and proteins may not function

Example of mutation altering amino acids

• Substitution can change the codon • Example: GCT → GAT • Alanine replaced by aspartic acid • Changes the resulting protein sequence

What is a frameshift mutation?

• Mutation where insertion or deletion changes the reading frame • Shifts all triplets after the mutation • Earlier frameshift = greater effect on protein • Affects many amino acids → big impact on protein structure

Why don’t mutations in multiples of 3 cause frameshifts?

• Because whole triplets are inserted/removed • The reading frame is preserved • Less disruptive compared to 1-base insertion/deletion

Frameshift example: deletion

• Original: TAT AGT CTT • Delete A → TAT GTC TT • Codons change → Tyrosine, Valine instead of original sequence • Alters multiple amino acids

Frameshift example: insertion

• Insert G into TAT AGT CTT → TAT GAG TCT T • New amino acids: Tyrosine, Glutamic acid, Serine • Alters many codons

Mutations can be spontaneous or caused by mutagens

• Spontaneous: DNA replication errors • Mutagenic agents increase mutation rate: UV light, ionising radiation, chemicals

Neutral mutations: same amino acid coded for

• Base change but amino acid doesn’t change • Because many amino acids have more than one codon • Example: TAT → TAC both code for tyrosine

Neutral mutations: chemically similar amino acids

• Mutation changes amino acid but replacement is chemically similar • Protein still works normally • Example: AGG (arginine) → AAG (lysine)

Neutral mutations: amino acid not involved in protein function

• Amino acid change far from enzyme active site • Protein structure and function unaffected • Overall organism unaffected

Why substitution mutations often have neutral effects

• They affect one codon only • Do not shift reading frame • Less likely to disrupt overall protein structure compared to frameshifts

Mutations that affect protein function

• Can make protein more or less active • May change shape (e.g., enzyme active site) • Can be beneficial or harmful

Beneficial mutation example: antibiotic resistance

• Bacteria gain mutations in enzyme genes • Enzymes break down more types of antibiotics • Increases bacterial survival

How beneficial mutations spread

• Advantageous allele passed on via natural selection • Individuals with mutation survive longer • Frequency of allele increases across generations

Mutations with harmful effects

• Decrease survival chances • Change protein structure/function negatively • Examples include genetic disorders and cancer-related mutations

Harmful mutation example: Cystic fibrosis

• Caused by deletion of 3 bases in CFTR gene • CFTR protein folds incorrectly → broken down • Leads to thick mucus, respiratory problems

Harmful mutation example: BRCA1 mutation

• BRCA1 protein normally repairs DNA breaks • Mutation → short, non-functional protein • Increases breast cancer risk due to uncontrolled cell division

Mutations affecting protein production

• Mutation at gene start may block RNA polymerase binding • Transcription cannot start → protein not produced • Loss of important protein causes disease

Example: Beta thalassaemia (HBB gene)

• Mutation in transcription initiation region • Little/no beta-globin produced • Leads to low haemoglobin, faulty red blood cells, poor oxygen transport • Causes severe symptoms such as weakness and growth problems

Exam tip: explaining mutation → protein effects

• Always describe: change in base sequence, change in amino acid sequence, and change in protein structure/function • Frameshift affects many amino acids → larger impact than substitution