Molecular Basis of Inheritance — Biology Class 12 Notes (CBSE & HBSE)
Free NCERT Biology notes for Molecular Basis of Inheritance (Class 12) on Siksha Sarovar, aligned to CBSE and Haryana Board (HBSE). This chapter is broken into 3 topics with clear explanations, formulas, solved examples and board-pattern practice — free to read, no sign-up required.
Board exam focus — Molecular Basis of Inheritance (CBSE & HBSE)
CBSE extensively tests DNA structure, Meselson-Stahl experiment, transcription (prokaryote and eukaryote differences), genetic code properties, translation, and lac operon regulation. HBSE focuses on DNA discovery experiments, Watson-Crick double helix features, replication enzymes, and transcription unit components.
DNA as Genetic Material and Structure
Experiments Proving DNA is Genetic Material
1. Griffith's Transformation Experiment (1928):
- Streptococcus pneumoniae (Pneumococcus): Smooth (S) strain = virulent (polysaccharide capsule); Rough (R) strain = non-virulent
- Experiment: Heat-killed S cells + live R cells injected into mouse → mouse DIED; virulent S bacteria isolated
- Conclusion: A "transforming principle" from heat-killed S cells transformed live R cells into S cells
- Griffith called this process transformation but didn't identify the transforming principle
2. Avery-MacLeod-McCarty Experiment (1944):
- Biochemically identified the transforming principle as DNA (not protein)
- Method: Digested proteins (protease) — transformation occurred; Digested DNA (DNase) — transformation STOPPED
- Destroyed RNA (RNase) — transformation occurred
- Conclusion: DNA is the transforming principle (genetic material)
3. Hershey-Chase Experiment (1952) — "Blender Experiment":
- Bacteriophage (T2 phage) infects E. coli
- Radioactive labelling:
- ³²P labels DNA (phosphorus in DNA backbone)
- ³⁵S labels protein (sulphur in amino acids)
- Procedure: Phage (labelled) → infects bacteria → blender (separate phage coat from bacteria) → centrifuge
- Results:
- ³²P (DNA) found INSIDE bacteria (in new phage particles)
- ³⁵S (protein) found in supernatant (phage coat, not inside bacteria)
- Conclusion: DNA (not protein) enters bacteria → DNA is the genetic material
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Why DNA over RNA?
| Property | DNA | RNA |
|---|---|---|
| Sugar | Deoxyribose (no 2'-OH) | Ribose (has 2'-OH) |
| Stability | More stable | Less stable (2'-OH allows hydrolysis) |
| Mutation rate | Lower | Higher |
| Repair mechanisms | Present | Absent (generally) |
Conclusion: DNA is better genetic material due to greater chemical stability. RNA acts as genetic material in some viruses (TMV, influenza, HIV) — these are called RNA viruses.
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Watson-Crick Model of DNA (1953)
James Watson and Francis Crick proposed the double helix structure of DNA (Nobel Prize 1962), based on Rosalind Franklin's X-ray crystallography data (Photo 51).
Key Features of B-DNA (most common form):
| Feature | Value/Description |
|---|---|
| Structure | Right-handed double helix |
| Strands | 2 anti-parallel strands (one 5'→3', other 3'→5') |
| Base pairs | A=T (2 hydrogen bonds); G≡C (3 hydrogen bonds) |
| Distance between base pairs | 3.4 Å (0.34 nm) |
| Pitch (one complete turn) | 34 Å (3.4 nm) |
| Base pairs per turn | 10 |
| Diameter of helix | 2 nm (20 Å) |
| Backbone | Phosphate-deoxyribose (outer) |
| Bases | Interior (stacked) |
Chargaff's Rules:
- A = T (equal amounts of adenine and thymine)
- G = C (equal amounts of guanine and cytosine)
- A + G = T + C (total purines = total pyrimidines)
- A + T / G + C ratio varies between species (species-specific)
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Nucleotide Structure
A nucleotide = nitrogenous base + deoxyribose sugar + phosphate group
Purines (double ring): Adenine (A), Guanine (G) Pyrimidines (single ring): Thymine (T), Cytosine (C) [in DNA]; Uracil (U) replaces T in RNA
Nucleotides are linked by 3'→5' phosphodiester bonds forming the sugar-phosphate backbone.
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DNA Packaging
Problem: Human genome = ~2 metres of DNA packed into a nucleus ~6 μm in diameter.
Solution: Hierarchical compaction:
| Level | Structure | Description |
|---|---|---|
| 1 | Nucleosome | 146 bp DNA wrapped ~1.65 turns around histone octamer (2×H2A, H2B, H3, H4); linked by H1 histone (linker) |
| 2 | 30 nm chromatin fibre | Nucleosomes compacted (solenoid structure — 6 nucleosomes per turn) |
| 3 | Loops | 30 nm fibre forms loops (50-100 kb each) anchored to protein scaffold |
| 4 | Metaphase chromosome | Maximum condensation during cell division |
Euchromatin: Loosely packed, transcriptionally active regions. Heterochromatin: Tightly packed, transcriptionally inactive regions (e.g., centromere, telomere, Barr body in females).
Histones: Positively charged proteins (rich in Lys and Arg) that bind negatively charged DNA electrostatically. Non-histone chromosomal proteins (NHC): Regulate gene expression; part of scaffold.
Diagram Indicator: [Diagram of DNA double helix showing 3.4 Å between base pairs, 34 Å pitch, 2 nm diameter, anti-parallel strands, A=T (2 H-bonds), G≡C (3 H-bonds); AND nucleosome structure showing DNA wrapped around histone octamer, H1 linker histone, and progression from nucleosome to solenoid to chromosome]
DNA Replication and Transcription
DNA Replication — Semi-Conservative Model
Watson and Crick (1953) proposed that DNA replication is semi-conservative: each daughter molecule has one old (parent) strand and one newly synthesised strand.
Proof — Meselson-Stahl Experiment (1958):
Method:
- E. coli grown for many generations in ¹⁵N (heavy nitrogen) medium → all DNA labelled with ¹⁵N (heavy)
- Bacteria transferred to ¹⁴N (light) medium for one generation → DNA extracted and centrifuged in CsCl density gradient
- After two generations and three generations, DNA bands analysed
Results:
| Generation | Band observed | Interpretation |
|---|---|---|
| 0 (before) | Heavy-heavy band only | All DNA is ¹⁵N-¹⁵N (heavy) |
| 1 (after 1 division) | Single hybrid band (¹⁵N-¹⁴N) | Each molecule has one ¹⁵N and one ¹⁴N strand |
| 2 (after 2 divisions) | Equal heavy-light and light-light | Two hybrid + two light molecules |
| 3 (after 3 divisions) | Mostly light, some hybrid |
Conclusion: Results match semi-conservative model (NOT conservative or dispersive models).
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Mechanism of DNA Replication
Key Enzymes and Proteins:
| Enzyme/Protein | Function |
|---|---|
| Helicase | Unwinds DNA double helix at replication fork |
| Topoisomerase (Gyrase) | Relieves torsional stress ahead of replication fork |
| SSB proteins | Single-Strand Binding proteins — stabilise unwound DNA strands |
| Primase | Synthesises short RNA primer (5-10 nucleotides) needed to start DNA synthesis |
| DNA Pol III | Main replicative enzyme — extends 5'→3', high processivity; has 3'→5' proofreading exonuclease |
| DNA Pol I | Removes RNA primer (5'→3' exonuclease) and fills gap with DNA |
| DNA Ligase | Joins Okazaki fragments (seals nicks in DNA backbone) |
Process:
- Helicase unwinds at origin of replication (ori) → replication fork
- Primase synthesises RNA primer on template strand
- DNA Pol III extends 3' end of primer → new DNA strand
- Leading strand: synthesised continuously in 5'→3' direction toward replication fork
- Lagging strand: synthesised in fragments (Okazaki fragments — ~1,000-2,000 nucleotides in prokaryotes) in 5'→3' direction away from fork
- DNA Pol I replaces RNA primers with DNA
- Ligase seals nicks → continuous daughter strands
In prokaryotes: Single origin of replication (oriC in E. coli) In eukaryotes: Multiple origins of replication (thousands) — replication is faster despite larger genome
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Transcription — Overview
Transcription is the synthesis of RNA from a DNA template by RNA polymerase. The information in DNA is copied into mRNA, which then carries the code to ribosomes for protein synthesis.
Central Dogma (Francis Crick, 1958): DNA → RNA → Protein (Replication → Transcription → Translation) Reverse transcription (RNA → DNA) occurs in retroviruses (HIV).
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Transcription in Prokaryotes (E. coli)
Template strand: The strand of DNA read by RNA polymerase (3'→5' direction). Also called antisense strand, minus strand, or non-coding strand. Coding strand: The strand with the same sequence as mRNA (except T→U). Also called sense strand or plus strand. NOT directly read by RNA pol.
Components:
| Component | Description |
|---|---|
| Promoter | Sequence upstream of gene where RNA pol binds; −10 region (Pribnow box: TATAAT) and −35 region (TTGACA) |
| Structural gene | The sequence transcribed (can be split into coding + non-coding in eukaryotes) |
| Terminator | Sequence where RNA pol detaches; Rho-dependent or Rho-independent |
**RNA Polymerase in E. coli:**
- Core enzyme: α₂ββ'ω (structural units)
- Sigma (σ) factor: recognises and binds promoter; dissociates after initiation
- Elongates RNA from 5'→3'
- One RNA pol synthesises all RNA types in prokaryotes (mRNA, rRNA, tRNA)
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Transcription in Eukaryotes
Three RNA polymerases:
| Polymerase | Location | Transcribes |
|---|---|---|
| RNA Pol I | Nucleolus | rRNA (28S, 18S, 5.8S) — large ribosomal RNAs |
| RNA Pol II | Nucleoplasm | mRNA precursors (hnRNA) — protein-coding genes |
| RNA Pol III | Nucleoplasm | tRNA, 5S rRNA, small nuclear RNAs |
Post-transcriptional modifications of hnRNA:
- 5' Capping: 7-methylguanosine cap added to 5' end → protects mRNA from degradation; needed for ribosome binding
- 3' Polyadenylation (Poly-A tail): 200+ adenine residues added to 3' end → protects from exonucleases; aids export from nucleus
- Splicing: Removal of introns (intervening non-coding sequences) and joining of exons (expressed coding sequences) by spliceosome (snRNPs + snRNA)
Result: Mature mRNA = 5' cap + 5' UTR + exons joined + 3' UTR + poly-A tail
hnRNA (heterogeneous nuclear RNA) = pre-mRNA in eukaryotes; contains introns + exons. mRNA = processed, mature; exported to cytoplasm for translation.
Diagram Indicator: [Diagram of Meselson-Stahl experiment showing CsCl gradient results after 0, 1, and 2 generations with heavy, hybrid, and light bands; AND diagram of eukaryotic pre-mRNA processing showing 5' capping, splicing (removal of introns), and 3' polyadenylation to produce mature mRNA]
Genetic Code, Translation and Gene Expression Regulation
The Genetic Code
The genetic code is the relationship between the nucleotide sequence in mRNA and the amino acid sequence in a protein.
Properties of the Genetic Code:
| Property | Description | Example |
|---|---|---|
| Triplet/Codon | 3 nucleotides code for 1 amino acid | AUG = Methionine (start) |
| Universal | Same code used by almost all organisms | UUU = Phenylalanine in bacteria, yeast, humans |
| Non-overlapping | Each base is part of only one codon | AUGCGU read as AUG-CGU (not AUG, UGC, GCG) |
| Commaless | No gap/punctuation between codons | Reads continuously |
| Degenerate | Multiple codons for one amino acid (synonymous codons) | Leu = UUA, UUG, CUU, CUC, CUA, CUG (6 codons) |
| Non-ambiguous | One codon = only one amino acid | UUU = only Phenylalanine |
| Ordered | Codons for same amino acid often differ only in 3rd position (wobble) | — |
Numbers:
- Total codons: 4³ = 64
- Sense (amino acid coding) codons: 61
- Nonsense/Stop/Termination codons: 3 (UAA — ochre, UAG — amber, UGA — opal)
- Start codon: AUG (also codes for methionine; formyl-methionine — fMet — in prokaryotes)
Wobble Hypothesis (Crick, 1966): The 3rd position (wobble position) of the codon can pair with more than one base in the anticodon → explains degeneracy. Example: GCU, GCC, GCA, GCG all code for Alanine — first two bases (GC) are fixed.
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Translation — Protein Synthesis
Translation is the synthesis of a polypeptide chain (protein) from the mRNA template, occurring at ribosomes.
Components Needed:
- mRNA (the message)
- Ribosomes (the molecular machine)
- tRNA (adaptor molecules — carry amino acids)
- Aminoacyl-tRNA synthetases (charge tRNA with correct amino acid)
- Initiation, elongation, termination factors
- GTP and ATP (energy)
Ribosome Structure:
| Feature | Prokaryote | Eukaryote |
|---|---|---|
| Sedimentation coefficient | 70S | 80S |
| Large subunit | 50S (23S rRNA + 5S rRNA + ~34 proteins) | 60S |
| Small subunit | 30S (16S rRNA + ~21 proteins) | 40S |
| Location | Cytoplasm | Cytoplasm (rough ER membrane) |
Sites on Ribosome: A site (Aminoacyl — incoming tRNA), P site (Peptidyl — tRNA with growing chain), E site (Exit — tRNA leaves).
Stages of Translation:
1. Initiation:
- 30S subunit + mRNA (at Shine-Dalgarno sequence in prokaryotes) + initiator tRNA (fMet-tRNA carrying fMet, anticodon UAC pairs with AUG)
- 50S joins → 70S initiation complex
- Initiator tRNA enters P site directly
2. Elongation:
- Aminoacyl-tRNA enters A site
- Peptidyl transferase (ribozyme activity of 23S rRNA) catalyses peptide bond formation between P-site amino acid and A-site amino acid
- Translocation: ribosome moves 3 nucleotides (one codon) along mRNA in 5'→3' direction (requires EF-G + GTP in prokaryotes)
- tRNA in P site moves to E site and exits; A-site tRNA moves to P site; new aminoacyl-tRNA enters A site
- Cycle repeats
3. Termination:
- Ribosome reaches a stop codon (UAA, UAG, UGA)
- No tRNA for stop codons — release factors (RF1, RF2) bind A site
- Peptidyl transferase adds water (hydrolysis) → polypeptide released
- Ribosome dissociates
Polyribosomes (Polysomes): Multiple ribosomes translating the same mRNA simultaneously → efficient protein synthesis.
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Lac Operon — Gene Expression Regulation
Jacob-Monod Model (1961): François Jacob and Jacques Monod proposed the operon concept for gene regulation in E. coli (Nobel Prize 1965).
Lac Operon — an inducible operon: Regulated by the presence/absence of lactose.
Components:
| Component | Description |
|---|---|
| Regulator gene (i) | Codes for Lac repressor protein (constantly expressed — constitutive) |
| Operator (O) | DNA sequence adjacent to promoter; Lac repressor binds here to block RNA pol |
| Promoter (P) | RNA pol binding site |
| Structural genes | lacZ (β-galactosidase — cleaves lactose), lacY (permease — transports lactose), lacA (transacetylase) |
Regulation:
When lactose is ABSENT:
- Lac repressor (active) binds operator → blocks RNA pol → no transcription → no enzymes
- This is the default OFF state
When lactose is PRESENT:
- Lactose (actually its isomer allolactose) binds repressor → conformational change → repressor cannot bind operator → RNA pol transcribes structural genes → β-galactosidase, permease, transacetylase produced → lactose metabolised
- Lactose is the inducer; allolactose is the co-inducer
Catabolite repression (glucose effect): When both glucose and lactose are present, glucose is preferred → catabolite repression prevents lac operon expression even with lactose present. CRP-cAMP (cAMP Receptor Protein) enhances lac operon transcription when glucose is absent → high cAMP + CRP binds upstream of promoter → increased transcription.
Diagram Indicator: [Diagram of lac operon showing (A) OFF state: regulator gene → repressor protein → binds operator → no transcription; (B) ON state: allolactose (inducer) → binds repressor → operator free → RNA pol transcribes lacZ, lacY, lacA; AND ribosome diagram showing A, P, E sites with incoming aminoacyl-tRNA, peptide bond formation, and translocation]
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