Molecular Basis of Inheritance Class 12 Notes वंशागति के आणविक आधार — कक्षा 12 जीव विज्ञान अध्याय 5

Revise these first (prerequisites)

• Basic idea of cell, nucleus and chromosome
• Proteins are made of amino acids (Class 11 Biomolecules)
• Chapter 4: concept of gene and allele
• Simple meaning of a hydrogen bond (Chemistry)

1. DNA = the instruction book of life

   Inside every cell, DNA is like a recipe book that states which protein is to be made and when. A gene is one 'chapter' of this book. Proteins do most of the work in the body, so the instructions written in DNA determine our traits.

2. Building block of DNA — the nucleotide

   DNA is made of small units called nucleotides: one nitrogenous base + one sugar (deoxyribose) + one phosphate. There are four bases: A, T, G, C. It is like writing an entire book using an alphabet of just 4 letters.

3. Double helix — a twisted ladder

   DNA is made of two strands that look like a twisted ladder. The 'steps' of the ladder are pairs of bases: A always pairs with T and G always pairs with C. This model was given by Watson and Crick in 1953.

4. Replication = making a copy

   Before a cell divides, DNA makes an exact copy of itself — replication (प्रतिकृतियन). Both strands unwind and each old strand acts as a template for a new strand. So every new DNA molecule has one old and one new strand (semiconservative).

5. DNA → RNA → Protein

   The information in DNA is first copied into mRNA (transcription / अनुलेखन), then the code of the mRNA is read to make protein (translation / स्थानांतरण). This flow is called the central dogma. Think of it this way: the master recipe (DNA) stays safe, and only its photocopy (mRNA) goes to the kitchen.

6. Genetic code — 3-letter words

   mRNA is read in groups of 3 bases — each group is a codon that specifies one amino acid. Reading starts at AUG (start) and stops at UAA, UAG or UGA (stop).

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As per NCERT 2026-27 — every point you need for the board exam.

1. Nucleotide

   Nitrogenous base + pentose sugar = nucleoside; + phosphate = nucleotide. Purines: A, G. Pyrimidines: C, T (DNA), U (RNA). Nucleotides are joined by 3'-5' phosphodiester bonds; the base and sugar are joined by an N-glycosidic bond.

2. DNA double helix

   Watson & Crick (1953), based on X-ray data of Wilkins and Rosalind Franklin. Two antiparallel strands; A=T (2 H-bonds), G≡C (3 H-bonds). Chargaff's rule: A = T, G = C. Pitch 3.4 nm, ~10 bp per turn, 0.34 nm between bp.

3. Length of DNA

   A human diploid cell has ~6.6 × 10⁹ bp → ~2.2 m of DNA. E. coli: 4.6 × 10⁶ bp. Lambda phage: 48502 bp.

4. DNA packaging

   Prokaryotes: nucleoid. Eukaryotes: an octamer of positively charged histones (lysine, arginine) + DNA = nucleosome (~200 bp). Beads-on-string → chromatin fibre. Euchromatin = loose, active; heterochromatin = dense, inactive.

5. Discovery of the genetic material

   Griffith (1928): Streptococcus pneumoniae (S & R strains) → transforming principle. Avery, MacLeod, McCarty: it is DNA. Hershey–Chase (1952): bacteriophage, radioactive ³²P (DNA) entered, ³⁵S (protein) did not → DNA is the genetic material.

6. RNA world

   The first genetic material was RNA. RNA also acts as a catalyst (ribozyme), but due to its 2'-OH group it is reactive and unstable. That is why the more stable DNA became the genetic material.

7. Replication

   Semiconservative — Meselson & Stahl (1958), using ¹⁵N in E. coli. Enzyme: DNA-dependent DNA polymerase (5'→3'); begins at the origin of replication, forming a replication fork. Leading strand is continuous, lagging strand is discontinuous (Okazaki fragments, joined by DNA ligase). Occurs in the S-phase.

8. Central dogma & transcription

   DNA → RNA → protein (Crick). Transcription unit: promoter, structural gene, terminator. Template strand 3'→5', coding strand 5'→3' (same sequence as mRNA, except T in place of U). Bacteria: a single RNA polymerase, σ factor (initiation), ρ factor (termination).

9. Eukaryotic transcription

   RNA pol I → rRNA (28S, 18S, 5.8S); pol II → hnRNA (precursor of mRNA); pol III → tRNA, 5S rRNA, snRNA. hnRNA undergoes splicing (introns removed, exons joined), capping (methyl guanosine triphosphate added at the 5' end) and tailing (poly-A added at the 3' end).

10. Genetic code

    Triplet code; 64 codons: 61 for amino acids, 3 stop (UAA, UAG, UGA). AUG = start + methionine. Unambiguous, degenerate, comma-less, nearly universal. George Gamow suggested the triplet code; Nirenberg and Khorana deciphered it.

11. tRNA & translation

    tRNA = adapter molecule (clover-leaf / inverted L); has an anticodon loop and an amino acid acceptor end. Charging (aminoacylation) → initiation (AUG) → elongation (peptide bond; 23S rRNA of ribosome = ribozyme) → termination (release factor). UTRs on both sides.

12. Lac operon (Jacob & Monod)

    Structural genes: z (β-galactosidase), y (permease), a (transacetylase); i gene = repressor. Lactose (inducer) inactivates the repressor → transcription ON. This is negative regulation.

13. HGP & DNA fingerprinting

    Human Genome Project (1990–2003): ~3 × 10⁹ bp; about 30,000 genes estimated; 99.9% bases are the same in all humans; chromosome 1 has the most genes (2968), Y the fewest (231); less than 2% of the genome codes for proteins; ~1.4 million SNPs. DNA fingerprinting (Alec Jeffreys): VNTR / satellite DNA probe, Southern blotting → forensics, paternity test.

The concept in depth — the why and the how. Everything stays within the NCERT syllabus.

1. Why is DNA better than RNA as genetic material?

   Every nucleotide of RNA has a 2'-OH group, which makes it reactive and easily degradable; DNA lacks it, so DNA is more stable. Thymine (in place of uracil) also gives DNA extra stability. Being reactive, RNA also mutates quickly — RNA viruses evolve fast. Hence DNA is better for stable storage, and RNA is better for fast expression/catalysis — and the first genetic material is believed to have been RNA (RNA world).

2. Why is the lagging strand discontinuous?

   DNA polymerase can add nucleotides only in the 5'→3' direction, and the two strands are antiparallel. Therefore, synthesis is continuous on one strand (template 3'→5'), and discontinuous on the other in small pieces (Okazaki fragments), which are later joined by DNA ligase. Replication starts only at the origin — this fact is used in the cloning vectors (ori) of Chapter 9.

3. The logic of the Meselson–Stahl experiment

   E. coli was first grown in ¹⁵N (heavy) medium, then shifted to ¹⁴N; DNA was separated by CsCl density gradient centrifugation. After 20 minutes (one generation), all the DNA was hybrid (intermediate); after 40 minutes, hybrid and light DNA were present in equal amounts. If replication were conservative, separate heavy and light bands would have appeared in the very first generation — so this is proof of semiconservative replication.

4. Extra steps of eukaryotic transcription

   Eukaryotes have three RNA polymerases: I (rRNAs 28S, 18S, 5.8S), II (hnRNA → mRNA), III (tRNA, 5S rRNA, snRNA). hnRNA contains introns, which are removed by splicing; a methyl guanosine triphosphate cap is added at the 5' end (capping) and 200–300 adenylate residues are added at the 3' end (tailing). Split genes (exons + introns) are probably an 'ancient' feature and a reminder of the RNA world.

5. Lac operon — genes switched ON/OFF as needed

   In the lac operon, the z (β-galactosidase), y (permease) and a (transacetylase) genes are transcribed together (polycistronic). The repressor made by the regulator gene i binds to the operator and blocks transcription. When lactose (inducer) is present, it binds to the repressor and inactivates it, and the genes are switched ON. This is negative regulation — the cell saves energy because the enzyme is made only when lactose is present.

6. Basis of DNA fingerprinting: polymorphism

   99.9% of the DNA of any two humans is identical; the differences lie in repetitive DNA. The copy number of VNTRs (satellite DNA) differs from person to person — they are detected by Southern blot/hybridisation using a probe. This pattern is inherited from the parents, so it is useful in paternity disputes and forensic cases. The technique was developed by Alec Jeffreys.

Common confusions — cleared up

1. Template strand vs Coding strand

   RNA is made from the template strand (3'→5'). The sequence of the coding strand (5'→3') is the same as the RNA (with U in place of T) — that is why the sequence is always written as that of the coding strand.

2. Degenerate vs Ambiguous code

   Degenerate = several codons for one amino acid (correct). Ambiguous = one codon for several amino acids — the genetic code is unambiguous; one codon specifies only one amino acid.

3. Nucleoside vs Nucleotide

   Nucleoside = base + sugar. Nucleotide = base + sugar + phosphate.

4. Euchromatin vs Heterochromatin

   Euchromatin is loosely packed, stains light and is transcriptionally active. Heterochromatin is densely packed, stains dark and is inactive.

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