Chemical nature of nucleic acids MCQs With Answer introduces B. Pharm students to the molecular chemistry and functional principles of DNA and RNA. This concise, keyword-rich overview covers nucleotides, nitrogenous bases, pentose sugars, phosphodiester bonds, base pairing, hydrogen bonding, base stacking, tautomerism, and physicochemical properties such as denaturation, melting temperature and UV absorption. It also highlights enzymatic processes, nucleotide modifications, backbone charge, GC content, and structural forms (A, B, Z). Clear understanding of these concepts is essential for pharmacology, drug–nucleic acid interactions, and biotechnological applications. Now let’s test your knowledge with 50 MCQs on this topic.
Q1. Which component of a nucleotide is responsible for the acidic character of nucleic acids?
- Nitrogenous base
- Pentose sugar
- Phosphate group
- Glycosidic bond
Correct Answer: Phosphate group
Q2. What sugar is found in RNA nucleotides?
- 2-deoxyribose
- Ribose
- Glucose
- Fructose
Correct Answer: Ribose
Q3. The bond linking the base to the sugar in a nucleotide is called:
- Phosphodiester bond
- Glycosidic bond
- Peptide bond
- Hydrogen bond
Correct Answer: Glycosidic bond
Q4. Which bases are pyrimidines in DNA?
- Adenine and Guanine
- Thymine and Cytosine
- Uracil and Adenine
- Guanine and Cytosine
Correct Answer: Thymine and Cytosine
Q5. Chargaff’s rule states that in double-stranded DNA, the amount of adenine equals the amount of:
- Guanine
- Thymine
- Cytosine
- Uracil
Correct Answer: Thymine
Q6. Which interaction primarily stabilizes the helical stacking of bases in DNA?
- Hydrogen bonding between bases
- Hydrophobic interactions and pi-stacking
- Phosphate-sugar covalent bonds
- Ionic interactions with sodium
Correct Answer: Hydrophobic interactions and pi-stacking
Q7. The phosphodiester linkage connects which atoms between adjacent nucleotides?
- 1′ carbon of sugar to base nitrogen
- 3′ hydroxyl of one sugar to 5′ phosphate of next sugar
- 5′ phosphate to base nitrogen
- 2′ hydroxyl to 3′ hydroxyl
Correct Answer: 3′ hydroxyl of one sugar to 5′ phosphate of next sugar
Q8. Which tautomeric shift can cause abnormal base pairing and mutations?
- Keto to enol shift in bases
- Alpha to beta sugar inversion
- Phosphate protonation
- Ribose ring opening
Correct Answer: Keto to enol shift in bases
Q9. Which form of DNA is most common under physiological hydration and is right-handed?
- Z-DNA
- A-DNA
- B-DNA
- Triple helix DNA
Correct Answer: B-DNA
Q10. UV absorbance at 260 nm is used to quantify nucleic acids because:
- Phosphate groups absorb strongly at 260 nm
- Nitrogenous bases have peak absorbance near 260 nm
- Sugars absorb at 260 nm
- Proteins have no absorbance at 260 nm
Correct Answer: Nitrogenous bases have peak absorbance near 260 nm
Q11. Hypochromicity observed upon DNA duplex formation refers to:
- Increase in absorbance on duplex formation
- Decrease in absorbance on duplex formation
- No change in absorbance on duplex formation
- Shift of absorbance peak to 280 nm
Correct Answer: Decrease in absorbance on duplex formation
Q12. Which factor increases DNA melting temperature (Tm)?
- Higher AT content
- Higher GC content
- Lower ionic strength
- Shorter strand length
Correct Answer: Higher GC content
Q13. Which ion commonly stabilizes negative charges on the phosphate backbone?
- Ca2+
- Mg2+
- Cl-
- K+
Correct Answer: Mg2+
Q14. In DNA, the glycosidic bond has which stereochemistry relative to the sugar?
- Alpha configuration
- Beta configuration
- Gamma configuration
- Delta configuration
Correct Answer: Beta configuration
Q15. Which modification is commonly found in eukaryotic mRNA but not in rRNA or tRNA?
- 5′ cap (7-methylguanosine)
- Pseudouridine
- Base methylation in cytosine of DNA
- 5-methylcytosine in tRNA
Correct Answer: 5′ cap (7-methylguanosine)
Q16. Which enzyme cleaves phosphodiester bonds at specific DNA sequences?
- DNA polymerase
- RNase A
- Restriction endonuclease
- Ligase
Correct Answer: Restriction endonuclease
Q17. The 5′ end of a nucleic acid strand is defined by which functional group?
- Free 3′ hydroxyl
- Free 5′ phosphate or hydroxyl
- Base attached to 1′ carbon
- Free 2′ hydroxyl
Correct Answer: Free 5′ phosphate or hydroxyl
Q18. Which type of RNA carries amino acids to the ribosome during translation?
- mRNA
- rRNA
- tRNA
- snRNA
Correct Answer: tRNA
Q19. Deamination of cytosine converts it into which base, leading to GC→AT transitions if not repaired?
- Uracil
- Thymine
- Adenine
- Guanine
Correct Answer: Uracil
Q20. Which chemical reagent is used for chain termination in Sanger sequencing?
- dNTPs
- ddNTPs (dideoxynucleotides)
- rNTPs
- ATP
Correct Answer: ddNTPs (dideoxynucleotides)
Q21. Which base is present in DNA but replaced by uracil in RNA?
- Cytosine
- Guanine
- Adenine
- Thymine
Correct Answer: Thymine
Q22. The enzymatic activity that synthesizes DNA from an RNA template is called:
- Reverse transcriptase
- DNA ligase
- RNase H
- Topoisomerase
Correct Answer: Reverse transcriptase
Q23. Which of the following describes Hoogsteen base pairing?
- Standard Watson-Crick pairing geometry
- Alternative pairing involving N7 and Hoogsteen face
- Triple helix formation exclusively with purines
- Base stacking between adjacent nucleotides
Correct Answer: Alternative pairing involving N7 and Hoogsteen face
Q24. Chemical synthesis of oligonucleotides commonly uses which protecting group chemistry?
- Fmoc chemistry for phosphoramidites
- Boc chemistry for sugars
- Phosphoramidite chemistry with DMT protection
- Carbodiimide coupling and benzyl protection
Correct Answer: Phosphoramidite chemistry with DMT protection
Q25. Which test distinguishes RNA from DNA based on sugar reactivity?
- Alkaline hydrolysis hydrolyzes RNA but not DNA
- Acid hydrolysis hydrolyzes RNA but not DNA
- DNA is hydrolyzed by RNase A
- Both are equally stable in alkali
Correct Answer: Alkaline hydrolysis hydrolyzes RNA but not DNA
Q26. Which base modification is common in bacterial DNA and involved in host restriction systems?
- 5-methylcytosine
- N6-methyladenine
- Pseudouridine
- Inosine
Correct Answer: N6-methyladenine
Q27. In nucleic acid chemistry, an inosine residue in tRNA most commonly results from modification of which base?
- Adenine deamination
- Guanine methylation
- Cytosine deamination
- Uracil methylation
Correct Answer: Adenine deamination
Q28. A polynucleotide chain has directionality. Which direction does DNA polymerase synthesize new strand?
- From 3′ to 5′
- From 5′ to 3′
- From 1′ to 2′
- From 2′ to 3′
Correct Answer: From 5′ to 3′
Q29. Which phenomenon explains faster renaturation (reassociation) kinetics for shorter complementary regions?
- Hypochromicity
- Cot analysis and second-order kinetics favor shorter sequences with higher concentration
- Denaturation temperature increase for shorter sequences
- Spontaneous fluorescence quenching
Correct Answer: Cot analysis and second-order kinetics favor shorter sequences with higher concentration
Q30. Which of the following nucleases specifically degrades single-stranded RNA?
- DNase I
- RNase A
- Exonuclease III
- Topoisomerase I
Correct Answer: RNase A
Q31. Methylation of cytosine at the 5 position in genomic DNA primarily affects:
- Base pairing fidelity during replication
- Gene expression via epigenetic regulation
- Immediate strand breakage
- Ribose conformation
Correct Answer: Gene expression via epigenetic regulation
Q32. Which of the following describes Z-DNA?
- Right-handed helix with 10 bp per turn
- Left-handed helix with zig-zag backbone
- Triple-stranded structure stabilized by Hoogsteen bonds
- RNA-DNA hybrid helical form
Correct Answer: Left-handed helix with zig-zag backbone
Q33. Which property allows ethidium bromide to act as an intercalating agent?
- Small size enabling groove binding
- Planar aromatic structure that inserts between base pairs
- Strong hydrogen bonding to phosphate groups
- Ability to methylate cytosine residues
Correct Answer: Planar aromatic structure that inserts between base pairs
Q34. The sugar pucker differs between A-DNA and B-DNA. Which pucker is typical of B-DNA?
- C3′-endo (North)
- C2′-endo (South)
- O4′-endo
- C1′-exo
Correct Answer: C2′-endo (South)
Q35. Which statement about base stacking energy is true?
- Base stacking contributes negligibly to helix stability
- Stacking is sequence-dependent and contributes significantly to stability
- Stacking only occurs in single-stranded RNA
- Stacking is purely ionic in nature
Correct Answer: Stacking is sequence-dependent and contributes significantly to stability
Q36. Which nucleoside lacks a phosphate and therefore is not a nucleotide?
- AMP (adenosine monophosphate)
- Adenosine
- ADP (adenosine diphosphate)
- ATP (adenosine triphosphate)
Correct Answer: Adenosine
Q37. Which reagent is commonly used to remove the 5′ dimethoxytrityl (DMT) protecting group during oligonucleotide synthesis?
- Trichloroacetic acid (TCA) or dichloroacetic acid (DCA)
- Sodium hydroxide
- Hydrazine
- EDTA
Correct Answer: Trichloroacetic acid (TCA) or dichloroacetic acid (DCA)
Q38. Which of the following best explains why RNA is more reactive chemically than DNA?
- Presence of 2′-hydroxyl group in ribose increases susceptibility to hydrolysis
- RNA has thymine which is reactive
- RNA lacks a phosphate backbone
- RNA has stronger base stacking than DNA
Correct Answer: Presence of 2′-hydroxyl group in ribose increases susceptibility to hydrolysis
Q39. Which modification is diagnostic of tRNA molecules and affects codon recognition?
- 5′ capping
- Pseudouridylation and various base methylations
- Polyadenylation at 3′ end
- Phosphorylation of bases
Correct Answer: Pseudouridylation and various base methylations
Q40. Alkylating agents that modify bases can cause mutagenesis by:
- Hydrolyzing phosphodiester bonds
- Adding alkyl groups that alter base pairing properties
- Removing ribose sugars
- Intercalating between base pairs
Correct Answer: Adding alkyl groups that alter base pairing properties
Q41. Which base pairing involves two hydrogen bonds?
- Guanine–Cytosine
- Adenine–Thymine
- Guanine–Thymine
- Adenine–Cytosine
Correct Answer: Adenine–Thymine
Q42. The phenomenon where single-stranded regions form hairpins or stem-loops is driven primarily by:
- Hydrophobic collapse of phosphates
- Intramolecular base pairing and stacking
- Enzymatic cleavage
- Random coil entropy only
Correct Answer: Intramolecular base pairing and stacking
Q43. Which sugar-carbon numbering is directly attached to the base in a nucleotide?
- 5′ carbon
- 1′ carbon
- 3′ carbon
- 2′ carbon
Correct Answer: 1′ carbon
Q44. Which analytical method can determine base composition and detect modified bases after hydrolysis?
- Gel electrophoresis
- High-performance liquid chromatography (HPLC)
- UV spectrophotometry alone
- Light microscopy
Correct Answer: High-performance liquid chromatography (HPLC)
Q45. Which chemical change is primarily responsible for spontaneous depurination?
- Hydrolysis of N-glycosidic bond leading to loss of purine base
- Oxidation of sugar to lactone
- Methylation of cytosine
- Deamination of adenine to hypoxanthine
Correct Answer: Hydrolysis of N-glycosidic bond leading to loss of purine base
Q46. Which property of nucleic acids is exploited in affinity purification using poly-dT columns?
- Complementarity between poly-dT and poly-A tails of mRNA
- Hydrophobicity of mRNA
- Stronger base stacking in tRNA
- 5′ cap binding to columns
Correct Answer: Complementarity between poly-dT and poly-A tails of mRNA
Q47. Which base analog can pair with both A and G, causing ambiguous pairing and mutagenesis?
- 5-bromouracil
- Azidothymidine
- 5-methylcytosine
- Inosine
Correct Answer: 5-bromouracil
Q48. The major groove of B-DNA is important because:
- It is too narrow for protein interactions
- It provides sequence-specific chemical information for protein binding
- Only minor groove binds transcription factors
- It contains phosphate groups exclusively
Correct Answer: It provides sequence-specific chemical information for protein binding
Q49. Chemical cleavage with dimethyl sulfate (DMS) methylates which atoms in purine bases and is used in footprinting studies?
- N1 of adenine and N3 of cytosine
- N7 of guanine and N3 of adenine
- N2 of guanine and O2 of thymine
- O4 of thymine and N1 of guanine
Correct Answer: N7 of guanine and N3 of adenine
Q50. Which concept explains why GC-rich regions are preferred binding sites for some DNA-binding proteins due to stiffness and minor groove features?
- Sequence-dependent DNA mechanics and groove geometry
- Random distribution of bases
- Complete lack of hydrogen bonding in GC pairs
- Absence of base stacking in GC regions
Correct Answer: Sequence-dependent DNA mechanics and groove geometry

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