Molecular Basis of Inheritance — Part A (NEET Biology Class 12): DNA Structure, Packaging & Replication
DNA Structure & the Double Helix
🎯 NEET priority: Highest-yield. 7–9 questions a year across both parts. Part A covers DNA structure and the classic experiments — the Hershey-Chase and Meselson-Stahl experiments and the exact double-helix numbers (3.4 nm pitch, 10 bp/turn, 0.34 nm per bp) are asked almost every year.
DNA structure — the exact numbers NEET asks
DNA was first identified as an acidic substance in the nucleus by Friedrich Meischer (1869), who named it 'Nuclein'. In 1953, James Watson and Francis Crick proposed the Double Helix model, based on the X-ray diffraction data of Maurice Wilkins and Rosalind Franklin and on Erwin Chargaff's rule that in double-stranded DNA, the ratios A:T and G:C are each constant and equal to one.
A nucleotide = nitrogenous base + pentose sugar + phosphate. Purines: adenine, guanine. Pyrimidines: cytosine, uracil, thymine. Base + sugar is joined by an N-glycosidic linkage (making a nucleoside); the phosphate joins the 5' carbon by a phosphoester linkage; two nucleotides join by a 3'-5' phosphodiester linkage.
The five salient features of the double helix
Feature | Detail |
Two chains | Sugar-phosphate backbone outside; bases project inside |
Anti-parallel polarity | One chain runs 5'→3', the other 3'→5' |
Base pairing | A=T via 2 hydrogen bonds; G≡C via 3 hydrogen bonds. A purine always pairs with a pyrimidine, keeping strand distance uniform |
Right-handed coil | Pitch = 3.4 nm; roughly 10 base pairs per turn; so distance between adjacent bp ≈ 0.34 nm |
Base stacking | Each base-pair plane stacks over the next — this, PLUS the H-bonds, gives the helix its stability |
Crick's Central Dogma: genetic information flows DNA → RNA → Protein. In some viruses the flow is reversed (RNA → DNA) — that process is reverse transcription.
Genome sizes worth remembering
Bacteriophage φ×174: 5386 nucleotides. Bacteriophage lambda: 48502 bp. E. coli: 4.6 × 10⁶ bp. Haploid human DNA: 3.3 × 10⁹ bp.
DNA Packaging & the Search for Genetic Material
Packaging of the DNA helix
A typical mammalian cell's DNA (6.6 × 10⁹ bp × 0.34 nm/bp) would stretch about 2.2 metres — far larger than the nucleus (~10⁻⁶ m). So it must be packaged.
In prokaryotes (e.g. E. coli), the negatively charged DNA is held by positively charged proteins in a region called the nucleoid, organised as large loops.
In eukaryotes, positively charged basic proteins called histones — rich in the basic amino acids lysine and arginine — form a histone octamer (8 molecules). The negatively charged DNA wraps around it to form a nucleosome, containing 200 bp of DNA. Under EM, nucleosomes appear as a 'beads-on-string' structure.
Beads-on-string → chromatin fibres → coiled and condensed at metaphase into chromosomes. Higher-order packaging needs Non-histone Chromosomal (NHC) proteins.
Euchromatin is loosely packed, stains light, and is transcriptionally ACTIVE. Heterochromatin is densely packed, stains dark, and is INACTIVE. This is a repeat NEET question — don't invert it.
The search for the genetic material — three landmark experiments
Experiment | Who & when | What was done | Conclusion |
Transforming principle | Frederick Griffith, 1928 | Streptococcus pneumoniae: S strain (smooth, mucous coat, virulent) killed mice; R strain (rough) did not. Heat-killed S alone was harmless — but heat-killed S + live R KILLED the mice, and live S was recovered | R strain was 'transformed' by some transforming principle from heat-killed S. But its biochemical nature was NOT identified |
Biochemical characterisation | Avery, MacLeod & McCarty, 1933–44 | Purified proteins, DNA and RNA from heat-killed S cells and tested which transformed live R cells. Proteases and RNases did NOT stop transformation; DNase DID | DNA alone caused transformation — so DNA is the hereditary material (though not all biologists were convinced) |
Unequivocal proof | Alfred Hershey & Martha Chase, 1952 | Grew bacteriophages on radioactive ³²P (labels DNA — protein has no phosphorus) or radioactive ³⁵S (labels protein — DNA has no sulphur). Infected E. coli, blended off the viral coats, centrifuged | Bacteria infected by ³²P phages WERE radioactive; those infected by ³⁵S phages were NOT. Therefore DNA, not protein, entered the bacteria — DNA is the genetic material |
DNA vs RNA & the RNA World
Properties of genetic material — why DNA beats RNA
A genetic material must be able to (1) replicate, (2) be chemically and structurally stable, (3) allow slow mutation for evolution, and (4) express itself as Mendelian characters.
Why DNA is more stable: RNA has a reactive 2'-OH group at every nucleotide, making it labile and easily degradable; RNA is also catalytic and therefore reactive. The presence of thymine instead of uracil confers further stability to DNA. Being double-stranded with a complementary strand, DNA also evolved repair mechanisms.
Where RNA wins: RNA can directly code for protein synthesis; DNA depends on RNA. RNA also mutates faster — which is why RNA viruses evolve faster and have shorter life spans. Conclusion: DNA is better for STORAGE, RNA is better for TRANSMISSION of genetic information.
RNA is the genetic material in some viruses — e.g. Tobacco Mosaic Virus (TMV) and QB bacteriophage.
RNA World
RNA was the FIRST genetic material. Essential life processes (metabolism, translation, splicing) evolved around RNA, which acted as both genetic material AND catalyst. But being catalytic made it reactive and unstable — so DNA evolved FROM RNA with chemical modifications for greater stability.
DNA Replication & Why This Matters for NEET
DNA Replication — semiconservative
Watson and Crick immediately proposed that each strand acts as a template, so each daughter DNA has one parental and one newly synthesised strand — semiconservative replication.
The Meselson–Stahl experiment (1958) — the proof
Step | What happened | Result |
Grow in ¹⁵N | E. coli grown many generations in ¹⁵NH₄Cl (heavy nitrogen — NOT radioactive, separated by density only) | All DNA is 'heavy'; distinguishable by CsCl density-gradient centrifugation |
Transfer to ¹⁴N, 20 min (I generation) | Cells moved to normal ¹⁴NH₄Cl medium; E. coli divides every 20 minutes | All DNA had HYBRID (intermediate) density — proving each new molecule has one old + one new strand |
40 min (II generation) | Allowed one more division | Equal amounts of HYBRID DNA and 'LIGHT' DNA |
Taylor and colleagues (1958) confirmed the same in Vicia faba (faba beans) using radioactive thymidine, proving chromosomal DNA also replicates semiconservatively.
The replication machinery
The main enzyme is DNA-dependent DNA polymerase. In E. coli (4.6 × 10⁶ bp), replication finishes in about 18 minutes — an average rate of roughly 2000 bp per second, and with very high accuracy (errors would be mutations).
Deoxyribonucleoside triphosphates serve a dual purpose — they are both the substrates AND the energy source (their two terminal phosphates are high-energy, like ATP).
Because separating the whole helix would cost too much energy, replication happens inside a small opening — the replication fork. DNA polymerase works only in the 5'→3' direction. So on the template with 3'→5' polarity replication is continuous, while on the 5'→3' template it is discontinuous — those fragments are joined by DNA ligase.
Replication starts only at a definite origin of replication — which is exactly why a vector is needed in recombinant DNA work (the vector supplies the origin). In eukaryotes, DNA replication occurs in the S phase, and failure of cell division after replication causes polyploidy.
Why this matters for NEET
High-value one-liners: Meischer named it Nuclein (1869); Chargaff's ratio A/T = G/C = 1; pitch 3.4 nm, 10 bp/turn, 0.34 nm/bp; A=T has 2 H-bonds, G≡C has 3; nucleosome = 200 bp on a histone octamer; Hershey-Chase used ³²P for DNA, ³⁵S for protein; Meselson-Stahl used ¹⁵N and CsCl.
Trap: ¹⁵N in Meselson-Stahl is a heavy but NOT radioactive isotope — separated purely by density. Hershey-Chase, by contrast, used genuinely radioactive isotopes. Also, Griffith identified the transforming principle's existence, but Avery-MacLeod-McCarty identified its chemical nature — don't credit Griffith with proving DNA is the genetic material.
Test Yourself: MCQs, PYQs & Active Recall
Answer these, then close the article and do an Active Recall. Reveal each answer only after you commit to one.
Practice Questions
Q1. DNA was first identified as an acidic substance in the nucleus and named 'Nuclein' by:
(a) Erwin Chargaff
(b) Rosalind Franklin
(c) Watson and Crick
(d) Friedrich Meischer
Show answer
Answer: (d) — Friedrich Meischer identified DNA in 1869 and named it Nuclein.
Q2. The X-ray diffraction data used by Watson and Crick was produced by:
(a) Chargaff and Meischer
(b) Hershey and Chase
(c) Maurice Wilkins and Rosalind Franklin
(d) Meselson and Stahl
Show answer
Answer: (c) — Watson and Crick built their 1953 double-helix model on X-ray diffraction data from Maurice Wilkins and Rosalind Franklin.
Q3. According to Chargaff's rule, in double-stranded DNA:
(a) A/T = G/C = 1
(b) A/T = G/C = 2
(c) Purines exceed pyrimidines
(d) A + T = G + C always
Show answer
Answer: (a) — Chargaff observed that the ratios of adenine to thymine and guanine to cytosine are each constant and equal to one.
Q4. The number of hydrogen bonds between guanine and cytosine is:
(a) Four
(b) One
(c) Two
(d) Three
Show answer
Answer: (d) — G pairs with C via three hydrogen bonds; A pairs with T via two.
Q5. The pitch of the DNA double helix and the number of base pairs per turn are:
(a) 34 nm and 10 bp
(b) 3.4 nm and 10 bp
(c) 3.4 nm and 20 bp
(d) 0.34 nm and 10 bp
Show answer
Answer: (b) — The pitch is 3.4 nm with roughly 10 base pairs per turn, giving about 0.34 nm between adjacent base pairs.
Q6. Two nucleotides in a polynucleotide chain are linked by a:
(a) 3'-5' phosphodiester linkage
(b) Peptide bond
(c) N-glycosidic linkage
(d) Phosphoester linkage
Show answer
Answer: (a) — A 3'-5' phosphodiester linkage joins two nucleotides; N-glycosidic joins base to sugar and phosphoester joins phosphate to sugar.
Q7. A typical nucleosome contains how many base pairs of DNA?
(a) 1000 bp
(b) 200 bp
(c) 100 bp
(d) 300 bp
Show answer
Answer: (b) — A typical nucleosome has 200 bp of DNA wrapped around a histone octamer.
Q8. Histones are rich in which basic amino acid residues?
(a) Serine and threonine
(b) Lysine and arginine
(c) Valine and leucine
(d) Glycine and alanine
Show answer
Answer: (b) — Histones are rich in lysine and arginine, whose positively charged side chains bind the negatively charged DNA.
Q9. Transcriptionally active chromatin is:
(a) Both equally
(b) Heterochromatin, densely packed
(c) Neither
(d) Euchromatin, loosely packed
Show answer
Answer: (d) — Euchromatin is loosely packed, stains light and is transcriptionally active; heterochromatin is densely packed and inactive.
Q10. In Griffith's experiment, mice died when injected with:
(a) Heat-killed S strain alone
(b) Live R strain alone
(c) Heat-killed S strain plus live R strain
(d) Live R strain plus heat-killed R strain
Show answer
Answer: (c) — Heat-killed S + live R killed the mice, and live S bacteria were recovered — showing R had been transformed.
Q11. Avery, MacLeod and McCarty showed that transformation was prevented by digestion with:
(a) Protease
(b) RNase
(c) DNase
(d) Lipase
Show answer
Answer: (c) — Proteases and RNases did not affect transformation, but DNase did — proving DNA is the transforming principle.
Q12. In the Hershey-Chase experiment, radioactive sulphur was used to label:
(a) DNA
(b) The bacterial cell wall
(c) Both DNA and protein
(d) Protein
Show answer
Answer: (d) — DNA contains no sulphur, so 35S labelled only protein; 32P labelled only DNA since protein has no phosphorus.
Q13. Which of the following makes RNA less stable than DNA?
(a) Having a phosphate backbone
(b) The reactive 2'-OH group at every nucleotide
(c) Being double stranded
(d) Presence of thymine
Show answer
Answer: (b) — The reactive 2'-OH group present at every RNA nucleotide makes RNA labile and easily degradable.
Q14. Semiconservative DNA replication means each daughter DNA molecule has:
(a) Two entirely new strands
(b) Two entirely parental strands
(c) One parental and one new strand
(d) A random mixture of fragments
Show answer
Answer: (c) — In semiconservative replication each daughter molecule retains one parental strand and one newly synthesised strand.
Q15. In the Meselson-Stahl experiment, the heavy isotope used was:
(a) 14C
(b) 15N (non-radioactive)
(c) Radioactive 32P
(d) Radioactive 35S
Show answer
Answer: (b) — 15N is a heavy but NOT radioactive isotope of nitrogen, separated from 14N purely on the basis of density in a CsCl gradient.
Q16. DNA polymerase catalyses polymerisation only in which direction?
(a) Direction varies by organism
(b) Both directions equally
(c) 3' to 5'
(d) 5' to 3'
Show answer
Answer: (d) — DNA-dependent DNA polymerase works only 5' to 3', which is why one strand is synthesised continuously and the other discontinuously.
Q17. Discontinuously synthesised DNA fragments are joined by the enzyme:
(a) DNA polymerase
(b) Helicase
(c) DNA ligase
(d) DNase
Show answer
Answer: (c) — DNA ligase joins the discontinuously synthesised fragments on the lagging strand template.
NEET Previous Year Questions (PYQs)
Real NEET previous-year questions on this chapter, with explanations in our own words.
Q18. Unequivocal proof that DNA is the genetic material came from the experiments of: (NEET PYQ)
(a) Hershey and Chase
(b) Griffith
(c) Avery, MacLeod and McCarty
(d) Meselson and Stahl
Show answer
Answer: (a) — Hershey and Chase (1952), using radioactively labelled bacteriophages, gave the unequivocal proof that DNA is the genetic material.
Q19. Which of these viruses has RNA as its genetic material? (NEET PYQ)
(a) Bacteriophage φ×174
(b) Tobacco Mosaic Virus
(c) Bacteriophage lambda
(d) Bacteriophage T2
Show answer
Answer: (b) — Tobacco Mosaic Virus and QB bacteriophage are examples where RNA, not DNA, is the genetic material.
Q20. In E. coli, replication of the entire genome is completed in approximately: (NEET PYQ)
(a) 18 minutes
(b) 2 minutes
(c) 20 hours
(d) 6 hours
Show answer
Answer: (a) — E. coli (4.6 x 10^6 bp) completes replication in about 18 minutes, at roughly 2000 bp per second.
Q21. The 'beads-on-string' structure seen under the electron microscope refers to: (NEET PYQ)
(a) Ribosomes on mRNA
(b) Chromosomes at metaphase
(c) Nucleosomes in chromatin
(d) The replication fork
Show answer
Answer: (c) — Nucleosomes, which are the repeating units of chromatin, appear as a beads-on-string structure under EM.
Q22. The haploid content of human DNA is approximately: (NEET PYQ)
(a) 4.6 x 10^6 bp
(b) 5386 nucleotides
(c) 3.3 x 10^9 bp
(d) 48502 bp
Show answer
Answer: (c) — Haploid human DNA content is about 3.3 x 10^9 base pairs; E. coli has 4.6 x 10^6 bp.
Q23. In the Meselson-Stahl experiment, DNA extracted after 40 minutes (second generation) consisted of: (NEET PYQ)
(a) All light DNA
(b) Equal amounts of hybrid and light DNA
(c) All heavy DNA
(d) All hybrid DNA
Show answer
Answer: (b) — After the second generation (40 min), the DNA was composed of equal amounts of hybrid density DNA and light DNA.
Q24. Deoxyribonucleoside triphosphates in replication act as: (NEET PYQ)
(a) Neither
(b) Substrates only
(c) Both substrates and energy source
(d) Energy source only
Show answer
Answer: (c) — They serve a dual purpose — acting as substrates and providing energy through their two terminal high-energy phosphates.
Active Recall Prompt
Write everything you can recall about Molecular Basis of Inheritance (Part A), naming each part first: DNA structure (Meischer, Watson and Crick, Wilkins and Franklin, Chargaff's rule, the linkages, and the five salient features with their exact numbers); the central dogma; DNA packaging (nucleoid, histones, nucleosome, euchromatin vs heterochromatin); the search for genetic material (Griffith's transforming principle, Avery-MacLeod-McCarty, Hershey-Chase — what each showed); properties of genetic material (why DNA is more stable than RNA); the RNA world; and DNA replication (semiconservative, the Meselson-Stahl experiment, DNA polymerase, the replication fork, continuous vs discontinuous synthesis, DNA ligase, origin of replication). Begin each fact with its topic and end it with a full stop.