Chapter 4 — Molecular Genetics Exercise Solutions
This chapter has the highest scoring potential in board exams. Master the steps of replication, transcription, and translation with exact enzyme names.
How to Use This Page
1. Start with the Key Concepts table for a rapid review of all essential terms. 2. Solve MCQs to check factual recall on DNA, RNA, and enzymes. 3. Fill in the Blanks for precise terminology and enzyme names. 4. True or False to catch and correct common misconceptions. 5. Match the Following to link enzymes, processes, and definitions. 6. Brief Answers (2-mark) for exam-style short responses. 7. Detailed Answers (5-mark) for structured, sub-pointed responses with diagram descriptions. 8. Common Mistakes to review before the exam. 9. Exam Checklist to ensure complete preparation.
Key Concepts (Quick Recap)
| Term | Definition |
|---|---|
| Nucleotide | Basic unit of DNA/RNA; consists of nitrogenous base + sugar + phosphate |
| Purines | Adenine (A) and Guanine (G) — double-ring nitrogenous bases |
| Pyrimidines | Thymine (T), Cytosine (C), Uracil (U) — single-ring nitrogenous bases |
| Chargaff's rule | In DNA, A = T and G = C; purines equal pyrimidines |
| Central dogma | DNA → RNA → Protein (flow of genetic information) |
| Semi-conservative replication | Each daughter DNA molecule has one old strand and one new strand |
| Replication fork | Y-shaped region where DNA strands separate during replication |
| Leading strand | Synthesised continuously in the 5'→3' direction |
| Lagging strand | Synthesised discontinuously as Okazaki fragments |
| Transcription | Synthesis of mRNA from a DNA template |
| Translation | Synthesis of protein from mRNA at the ribosome |
| Codon | Triplet of nucleotides on mRNA that codes for an amino acid |
| Anticodon | Triplet of nucleotides on tRNA complementary to a codon |
| Start codon | AUG — codes for Methionine and initiates translation |
| Stop codons | UAA, UAG, UGA — terminate translation; no amino acid assigned |
| Lac operon | Inducible operon in E. coli that regulates lactose metabolism |
| Promoter | DNA sequence where RNA polymerase binds to initiate transcription |
| Operator | DNA sequence where repressor protein binds to block transcription |
| Exon | Coding sequence in a gene that is retained in mature mRNA |
| Intron | Non-coding sequence in a gene that is removed during splicing |
I. Choose the Best Answer (MCQs)
1. The double helix model of DNA was proposed by: (a) Meselson and Stahl (b) Watson and Crick (c) Chargaff (d) Morgan
2. According to Chargaff's rule, if a DNA sample has 20% adenine, what is the percentage of guanine? (a) 20% (b) 30% (c) 30% (d) 40%
3. Semi-conservative replication of DNA was proved by: (a) Watson and Crick (b) Meselson and Stahl (c) Hershey and Chase (d) Griffith
4. Which enzyme unwinds the DNA double helix during replication? (a) DNA polymerase (b) Helicase (c) Ligase (d) Primase
5. Okazaki fragments are synthesised on the: (a) Leading strand (b) Lagging strand (c) Both strands (d) Template strand
6. The enzyme that joins Okazaki fragments is: (a) Helicase (b) DNA Polymerase III (c) DNA Ligase (d) Primase
7. In the lac operon, what happens when lactose is present? (a) Repressor binds operator and genes are OFF (b) Lactose binds repressor, repressor releases operator, genes are ON (c) Lactose binds promoter and genes are OFF (d) Repressor binds lactose and genes are OFF
8. Which of the following is a stop codon? (a) AUG (b) UAA (c) GCU (d) UAC
9. RNA that carries amino acids to the ribosome is: (a) mRNA (b) tRNA (c) rRNA (d) snRNA
10. The process of removing introns and joining exons is called: (a) Capping (b) Tailing (c) Splicing (d) Translation
11. Which enzyme synthesises the RNA primer during DNA replication? (a) DNA Polymerase I (b) DNA Polymerase III (c) Primase (d) Ligase
12. The P-site of the ribosome holds: (a) The incoming aminoacyl-tRNA (b) The tRNA carrying the growing polypeptide chain (c) The mRNA start codon (d) The released tRNA
II. Fill in the Blanks
1. The sugar present in DNA is deoxyribose and in RNA is ribose. 2. Adenine pairs with thymine in DNA and with uracil in RNA. 3. The number of hydrogen bonds between adenine and thymine is 2 and between guanine and cytosine is 3. 4. DNA replication occurs during the S phase of the cell cycle. 5. The enzyme that synthesises new DNA strands during replication is DNA Polymerase III. 6. The start codon is AUG which codes for Methionine. 7. The three stop codons are UAA, UAG, and UGA. 8. In eukaryotes, pre-mRNA processing includes 5' capping, 3' poly-A tail addition, and splicing. 9. The central dogma of molecular biology was proposed by Francis Crick. 10. In the lac operon, the structural genes are lacZ, lacY, and lacA.
III. True or False (with corrections for false ones)
IV. Match the Following
| Column A | Column B |
|---|---|
| 1. Helicase | d. Unwinds DNA double helix |
| 2. Primase | g. Synthesises RNA primer |
| 3. DNA Polymerase III | a. Synthesises new DNA strand |
| 4. DNA Ligase | e. Joins Okazaki fragments |
| 5. RNA Polymerase | h. Catalyses transcription |
| 6. Topoisomerase | b. Relieves tension ahead of replication fork |
| 7. DNA Polymerase I | c. Removes RNA primer |
| 8. Peptidyl transferase | f. Forms peptide bonds during translation |
V. Answer Briefly (2-mark)
1. What is the central dogma of molecular biology? The central dogma describes the flow of genetic information: DNA → RNA → Protein. DNA is transcribed into mRNA (transcription), and mRNA is translated into protein (translation). This was proposed by Francis Crick. An exception to the central dogma is reverse transcription, found in retroviruses like HIV, where RNA is converted to DNA by the enzyme reverse transcriptase.
2. Differentiate between DNA and RNA. DNA is double-stranded with deoxyribose sugar and the nitrogenous base thymine; it is found mainly in the nucleus and is long-lived, storing genetic information. RNA is single-stranded with ribose sugar and the nitrogenous base uracil (instead of thymine); it is found in both the nucleus and cytoplasm, is short-lived, and carries out protein synthesis. There are three types of RNA — mRNA (messenger), tRNA (transfer), and rRNA (ribosomal) — each with a distinct role.
3. What is semi-conservative replication? Name the scientists who proved it. Semi-conservative replication means that each daughter DNA molecule contains one old (parental) strand and one newly synthesised strand. The two strands of the parent DNA separate, and each serves as a template for synthesising a new complementary strand. This was experimentally proved by Meselson and Stahl in 1958 using E. coli grown in medium containing heavy nitrogen (N-15) and then transferred to light nitrogen (N-14). After one replication, the DNA showed intermediate density, confirming semi-conservative replication.
4. What are Okazaki fragments? Why are they formed? Okazaki fragments are short DNA fragments (1000-2000 nucleotides in prokaryotes, 100-200 in eukaryotes) synthesised on the lagging strand during DNA replication. They are formed because DNA polymerase can only synthesise DNA in the 5'→3' direction, but the lagging strand template runs in the 3'→5' direction. Therefore, the lagging strand is synthesised discontinuously in short fragments, each initiated by an RNA primer. The fragments are later joined by DNA ligase to form a continuous strand.
5. Define transcription. Name the enzyme involved. Transcription is the process of synthesising RNA from a DNA template. It occurs in the nucleus (in eukaryotes) and is catalysed by the enzyme RNA polymerase. The DNA strand that serves as the template is called the antisense strand (or template strand), and the complementary strand is the coding strand (or sense strand). Transcription has three stages: initiation (RNA polymerase binds to promoter), elongation (RNA is synthesised 5'→3'), and termination (RNA polymerase reaches terminator sequence).
6. What is the lac operon? Explain briefly. The lac operon is an inducible operon in E. coli that regulates the metabolism of lactose. It consists of structural genes (lacZ for beta-galactosidase, lacY for permease, lacA for transacetylase), a promoter, an operator, and a regulator gene (lacI). When lactose is absent, the lacI gene produces a repressor protein that binds to the operator, blocking transcription. When lactose is present, it acts as an inducer and binds to the repressor, causing the repressor to release from the operator. This allows RNA polymerase to transcribe the structural genes.
VI. Answer in Detail (5-mark)
1. Describe the structure of DNA as proposed by Watson and Crick. The Watson and Crick model of DNA (1953) is based on X-ray diffraction data by Rosalind Franklin:
- Double helix: DNA consists of two polynucleotide strands wound around each other in a right-handed helix.
- Antiparallel strands: The two strands run in opposite directions — one 5'→3' and the other 3'→5'. This is called antiparallel orientation.
- Sugar-phosphate backbone: The outer backbone is made of alternating deoxyribose sugar and phosphate groups, connected by phosphodiester bonds.
- Base pairing: Nitrogenous bases project inward and pair specifically — Adenine (A) pairs with Thymine (T) through 2 hydrogen bonds, and Guanine (G) pairs with Cytosine (C) through 3 hydrogen bonds. This is Chargaff's rule.
- Base stacking: The paired bases are stacked one above the other, perpendicular to the helix axis, stabilised by hydrophobic interactions and van der Waals forces.
- Dimensions: One full turn of the helix (pitch) is 3.4 nm, containing 10 base pairs. The distance between adjacent base pairs is 0.34 nm. The diameter of the helix is approximately 2 nm.
- Diagram description: Draw the double helix showing two strands wound around a common axis. Label the sugar-phosphate backbone on the outside, base pairs (A-T, G-C) on the inside, phosphodiester bonds, and hydrogen bonds between base pairs. Show the antiparallel orientation with 5' and 3' ends.
2. Explain the process of DNA replication with the role of each enzyme. DNA replication is the process by which a DNA molecule makes an identical copy of itself. It is semi-conservative:
- Origin of replication: Replication begins at specific sequences called origins of replication. In prokaryotes, there is one origin; in eukaryotes, there are many.
- Unwinding (Helicase): The enzyme helicase unwinds and separates the two strands of the DNA double helix, forming the replication fork.
- Relieving tension (Topoisomerase): As helicase unwinds the DNA, supercoiling occurs ahead of the fork. Topoisomerase (DNA gyrase in prokaryotes) relieves this tension by cutting and rejoining the DNA strands.
- Primer synthesis (Primase): DNA polymerase cannot start synthesis de novo. Primase synthesises short RNA primers complementary to the template strand.
- Elongation (DNA Polymerase III): DNA Polymerase III adds nucleotides to the 3' end of the primer, synthesising the new strand in the 5'→3' direction. The leading strand is synthesised continuously. The lagging strand is synthesised discontinuously as Okazaki fragments.
- Primer removal (DNA Polymerase I): DNA Polymerase I removes the RNA primers and fills the gaps with DNA nucleotides.
- Joining fragments (DNA Ligase): DNA Ligase joins the Okazaki fragments by forming phosphodiester bonds, creating a continuous strand.
- Proofreading: DNA Polymerase III also has 3'→5' exonuclease (proofreading) activity, correcting mismatched nucleotides.
3. Explain the process of transcription in eukaryotes with the stages and processing of pre-mRNA. Transcription is the synthesis of mRNA from a DNA template, catalysed by RNA polymerase:
1. 5' capping: A 7-methylguanosine cap is added to the 5' end. This protects the mRNA from degradation and helps ribosome binding during translation. 2. 3' poly-A tail: A chain of 200-250 adenine nucleotides is added at the 3' end. This protects mRNA from degradation and aids in export from the nucleus. 3. Splicing: Introns (non-coding sequences) are removed and exons (coding sequences) are joined together by the spliceosome (complex of snRNPs). This produces mature mRNA that is ready for translation.
- Initiation: RNA polymerase II binds to the promoter region of the gene with the help of transcription factors. The promoter contains the TATA box (in eukaryotes). The DNA double helix unwinds, exposing the template strand.
- Elongation: RNA polymerase moves along the template strand in the 3'→5' direction, synthesising RNA in the 5'→3' direction. Ribonucleotides are added complementary to the DNA template: A pairs with U (in RNA), T pairs with A, G pairs with C, C pairs with G.
- Termination: RNA polymerase reaches the terminator sequence and releases the newly formed RNA. In eukaryotes, this results in pre-mRNA (primary transcript).
- Processing of pre-mRNA: Eukaryotic pre-mRNA undergoes three modifications before becoming mature mRNA:
- Diagram description: Draw a gene showing promoter, exons, and introns. Show the three processing steps: capping at 5' end, poly-A tail at 3' end, and splicing (removal of introns). Label the resulting mature mRNA with cap, exons joined together, and poly-A tail.
4. Explain the process of translation with the role of ribosomes, mRNA, and tRNA. Translation is the synthesis of protein from mRNA at the ribosome:
1. Aminoacyl-tRNA entry: The next aminoacyl-tRNA enters the A-site, carrying the amino acid specified by the next codon. 2. Peptide bond formation: Peptidyl transferase (a ribozyme in the large subunit) catalyses the formation of a peptide bond between the amino acid in the P-site and the one in the A-site. 3. Translocation: The ribosome moves one codon forward along the mRNA. The tRNA in the P-site moves to the E-site and exits. The tRNA in the A-site (now carrying the growing polypeptide) moves to the P-site. The A-site is now empty for the next aminoacyl-tRNA.
- Activation of amino acids: Each amino acid is activated by ATP and linked to its specific tRNA by aminoacyl-tRNA synthetase, forming aminoacyl-tRNA.
- Initiation: The small ribosomal subunit binds to the mRNA at the start codon (AUG). The initiator tRNA carrying methionine (in prokaryotes, formyl-methionine) binds to the start codon at the P-site. The large ribosomal subunit then joins, forming the complete ribosome.
- Elongation: This occurs in three steps:
- Termination: When a stop codon (UAA, UAG, or UGA) enters the A-site, no tRNA matches it. Release factors bind to the A-site, causing the polypeptide to be released from the tRNA in the P-site. The ribosome subunits dissociate.
- Post-translational modifications: The polypeptide may undergo folding, cleavage, addition of chemical groups (phosphorylation, glycosylation), or targeting to specific cellular locations.
- Diagram description: Draw a ribosome with three sites (E, P, A) on the large subunit. Show mRNA threaded through the ribosome with codons visible. Show tRNAs in the A-site (incoming) and P-site (growing chain). Label the peptide bond formation and translocation steps.
DNA Structure — Key Points
- Double helix model: Watson and Crick (1953), based on X-ray data by Rosalind Franklin.
- Antiparallel strands: one 3'→5', other 5'→3'.
- Base pairing: A=T (2 hydrogen bonds), G≡C (3 hydrogen bonds).
- Sugar-phosphate backbone forms the outer rails.
- One full turn (pitch) = 3.4 nm, 10 base pairs.
DNA Replication — Enzymes
| Enzyme | Function |
|---|---|
| Helicase | Unwinds and separates double helix |
| Primase | Synthesises RNA primer |
| DNA Polymerase III | Synthesises new DNA strand (5'→3') |
| DNA Polymerase I | Removes RNA primer, fills gap |
| DNA Ligase | Joins Okazaki fragments |
| Topoisomerase | Relieves tension ahead of replication fork |
Leading strand — synthesised continuously in 5'→3'. Lagging strand — synthesised discontinuously as Okazaki fragments.
Transcription — Steps
1. Initiation: RNA polymerase binds to promoter region. 2. Elongation: RNA synthesised 5'→3', complementary to template strand. 3. Termination: RNA polymerase reaches terminator sequence, RNA released.
In eukaryotes: pre-mRNA undergoes processing:
- 5' capping (7-methylguanosine)
- 3' poly-A tail addition
- Splicing — introns removed, exons joined
Translation — Codon Table Essentials
- Start codon: AUG (Methionine)
- Stop codons: UAA, UAG, UGA (no amino acid)
- Codons are non-overlapping, non-ambiguous, degenerate (multiple codons for same amino acid).
Ribosomes: 3 sites — E (exit), P (peptidyl), A (aminoacyl).
Gene Regulation — Lac Operon
| Component | Role |
|---|---|
| Structural genes (lacZ, lacY, lacA) | Code for enzymes to metabolise lactose |
| Promoter | Binding site for RNA polymerase |
| Operator | Binding site for repressor |
| Regulator gene (lacI) | Codes for repressor protein |
- No lactose: Repressor binds operator → genes OFF.
- Lactose present: Lactose (inducer) binds repressor → repressor released → genes ON.
Worked Examples
Example 1 — Complementary strand
Write the complementary DNA strand for 5'-ATGCTAGC-3'.
Example 2 — Chargaff's rule
In a DNA sample, adenine is 30%. Find the % of T, G, and C.
Example 3 — mRNA from a template strand
Transcribe the DNA template 3'-TACGGT-5'.
Common Mistakes to Avoid
1. ❌ Writing thymine in RNA instead of uracil ✅ RNA contains uracil (U) in place of thymine (T). DNA has T; RNA has U.
2. ❌ Saying DNA polymerase works in the 3'→5' direction ✅ DNA polymerase can only synthesise in the 5'→3' direction. It reads the template in 3'→5' and synthesises the new strand 5'→3'.
3. ❌ Confusing template strand (antisense) with coding strand (sense) ✅ The template strand (antisense) is the strand that RNA polymerase reads. The coding strand (sense) has the same sequence as the mRNA (with T instead of U).
4. ❌ Forgetting that stop codons are NOT recognised by tRNA ✅ Stop codons (UAA, UAG, UGA) have no corresponding tRNA. Release factors bind instead, terminating translation.
5. ❌ Confusing leading strand with lagging strand synthesis ✅ Leading strand = continuous synthesis in 5'→3' direction toward the fork. Lagging strand = discontinuous synthesis as Okazaki fragments away from the fork.
6. ❌ Stating that introns are coding sequences ✅ Introns are non-coding sequences removed during splicing. Exons are coding sequences retained in mature mRNA.
7. ❌ Writing that RNA polymerase requires a primer ✅ RNA polymerase does NOT require a primer — it initiates transcription directly at the promoter. DNA polymerase requires an RNA primer.
8. ❌ Saying the lac operon is always ON ✅ The lac operon is inducible — it is OFF when lactose is absent (repressor bound) and ON when lactose is present (inducer binds repressor).
Exam Checklist
- [ ] Can you describe the Watson and Crick model of DNA with dimensions and base pairing?
- [ ] Can you state and apply Chargaff's rule to calculate base percentages?
- [ ] Can you explain semi-conservative replication and the Meselson-Stahl experiment?
- [ ] Can you list all replication enzymes and their functions?
- [ ] Can you differentiate between leading strand and lagging strand synthesis?
- [ ] Can you explain the three stages of transcription (initiation, elongation, termination)?
- [ ] Can you describe the three processing steps of pre-mRNA in eukaryotes?
- [ ] Can you explain translation with the roles of mRNA, tRNA, and ribosomes (E, P, A sites)?
- [ ] Can you identify start and stop codons?
- [ ] Can you explain the lac operon with all components (structural genes, promoter, operator, regulator)?
- [ ] Can you differentiate between DNA and RNA (at least 5 differences)?
- [ ] Can you write a complementary DNA strand and transcribe DNA to mRNA?
- [ ] Can you explain the central dogma and its exception (reverse transcription)?