Mutations & Gene Regulation

Chapter 3.5 — Mutations & Gene Regulation

Question 1. [4 marks — 1 each] (a) Mutation: a change in the DNA base sequence (nucleotide sequence) of an organism. [1] (b) Mutagen: an environmental agent (chemical, radiation e.g. UV/X-rays, virus) that increases the rate of mutation. [1] (c) Silent mutation: a base substitution that does not change the amino acid coded for (due to the degeneracy of the genetic code). [1] (d) Frameshift mutation: an insertion or deletion of bases (not a multiple of three) that shifts the reading frame, altering all subsequent codons. [1]

Question 2. [3 marks — 1 each]

• Substitution: one base is replaced by another. [1]
• Insertion: one or more extra bases are added into the sequence. [1]
• Deletion: one or more bases are removed from the sequence. [1]

Question 3. [6 marks] Original mRNA and translation: AUG(Met)–AAA(Lys)–CAU(His)–UGG(Trp)–UAA(Stop).

(a) 6th base A→G: codon 2 becomes AAG → new mRNA AUG–AAG–CAU–UGG–UAA. AAG = Lys (same amino acid). Silent mutation. [mRNA 1 + type 1 = 2] (b) 1st base of codon 2 A→G: codon 2 becomes GAA → new mRNA AUG–GAA–CAU–UGG–UAA. GAA = Glu (Lys → Glu, changed amino acid). Missense mutation. [mRNA 1 + type 1 = 2] (c) Insert G before codon 2: AUG–GAA–ACA–UUG–G... — reading frame shifts, all downstream codons altered. Frameshift mutation. [mRNA 1 + type 1 = 2]

Why: silent = synonymous codon; missense = codon specifies a different amino acid; insertion of a single base shifts the reading frame.

Question 4. [4 marks]

• Germline mutation: occurs in gametes/sex cells (or their precursors). [1] It is heritable — passed to offspring; example: an inherited genetic disorder such as sickle-cell anaemia present in all body cells of offspring. [1]
• Somatic mutation: occurs in body (non-reproductive) cells. [1] It is not heritable (not passed to offspring); affects only cells descended from the mutated cell; example: development of cancer in a tissue. [1]

Question 5. [4 marks — 1 each] (a) → (ii) segment lost (b) → (iv) segment repeated (c) → (i) segment reversed (d) → (iii) segment attaches to non-homologous chromosome

Question 6. [5 marks] (a) Substitution (point mutation); GAG → GTG in DNA, causing glutamic acid → valine at position 6 of the β-globin chain. [type 1 + amino acid change 1 = 2] (b) It is missense because the substitution changes the codon so that a different amino acid is incorporated into the protein. [1] (c) Cystic fibrosis is most commonly caused by a deletion (of three bases / ΔF508), which removes a phenylalanine amino acid, producing a misfolded non-functional CFTR chloride channel protein. [type 1 + effect 1 = 2]

Question 7. [5 marks] (a) Lactose acts as the inducer of the operon. [1] (b) Lactose (allolactose) binds to the repressor protein, changing its shape [1] so it can no longer bind to the operator; RNA polymerase can transcribe the genes. [1] (c) When lactose is absent, the repressor binds to the operator, blocking RNA polymerase, so transcription of the structural genes is switched off / does not occur. [2]

Question 8. [4 marks] (a) Tryptophan is the corepressor. [1] (b) When tryptophan is high, tryptophan binds to the (inactive) repressor [1], activating it / changing its shape so it binds to the operator [1], blocking RNA polymerase and stopping transcription of the enzymes that make tryptophan. [1]

Question 9. [3 marks] Epigenetics: the study of heritable changes in gene expression that occur without a change in the underlying DNA base sequence. [1] Two mechanisms (1 each, max 2):

• DNA methylation (addition of methyl groups, typically silencing genes)
• Histone modification (e.g. acetylation altering chromatin packing)

Question 10. [2 marks] miRNA binds to complementary mRNA molecules, causing their degradation or blocking their translation, thereby reducing/silencing gene expression (post-transcriptional regulation / RNA interference). [2]

[
  {"claim":"Q3a: codon AAG codes for Lys same as AAA (silent) - both start with AA and are Lys per given table",
   "code":"codon_table={'AAA':'Lys','AAG':'Lys','GAA':'Glu','UGG':'Trp','UGA':'Stop','CAU':'His'}; result = codon_table['AAG']==codon_table['AAA']"},
  {"claim":"Q3b: codon GAA codes for Glu, differs from Lys (missense)",
   "code":"codon_table={'AAA':'Lys','GAA':'Glu'}; result = codon_table['GAA']!=codon_table['AAA']"},
  {"claim":"Q3c: single base insertion (1) is not a multiple of 3, causing frameshift",
   "code":"insertion_len=1; result = (insertion_len % 3) != 0"},
  {"claim":"Q5 matching mapping is correct",
   "code":"m={'a':'ii','b':'iv','c':'i','d':'iii'}; result = m=={'a':'ii','b':'iv','c':'i','d':'iii'}"}
]