Molecular Basis of Inheritance
🧬 5.1 THE DNA – ✨ Core Concept
DNA (Deoxyribonucleic Acid) is the fundamental hereditary molecule found in nearly all living organisms. It stores, transmits, and expresses genetic information and is capable of replication, mutation, and transcription. In some viruses, however, RNA serves as the genetic material.
🎯 Learning Goals:
- By the end of this section, students should be able to: Identify the chemical structure of DNA
- Explain the components of a nucleotide
- Distinguish DNA from RNA
- Understand how DNA structure relates to function
- Recall key historical contributions to DNA structure
- Appreciate the uniqueness and universality of DNA
📖 5.1.2 Historical Milestone: Discovery of DNA Structure
👨🔬 Friedrich Miescher (1869)
- Isolated an acidic substance from pus cells → called it “nuclein”
- Later identified as DNA
👨🔬 Chargaff’s Rule (Erwin Chargaff, 1950)
- First Parity Rule: In a double-stranded DNA molecule, the amount of adenine (A) is equal to the amount of thymine (T), and the amount of guanine (G) is equal to the amount of cytosine (C).
- This can be expressed as A = T and G = C.
- Additionally, the total amount of purines (A+G) equals the total amount of pyrimidines (T+C).
Base Pairing Rule:
- A = T
- G ≡ C
- Total purines = pyrimidines in double-stranded DNA
🔬 Watson & Crick’s Double Helix Model (1953)
Based on:
- Chargaff’s rules
- Rosalind Franklin’s X-ray diffraction image
🔥 Salient Features of the Double Helix Model:
- Two strands wound around each other → Right-handed helix
- Antiparallel orientation:
- One strand runs 5’→3’
- Other strand runs 3’→5’
- Base Pairing:
- A = T (via 2 hydrogen bonds)
- G ≡ C (via 3 hydrogen bonds)
- Uniform width (2 nm) maintained by pairing 1 purine + 1 pyrimidine
- One complete turn = 10 base pairs = 3.4 nm
- Base stacking stabilizes the structure (π–π interactions)
📌 Hydrogen bonds and hydrophobic interactions stabilize the double helix 🧠 Mnemonic to remember base bonds: “AT2 (A–T has 2 bonds) & GC3 (G–C has 3 bonds)”
🔁 Complementarity of DNA Strands
- Each strand is complementary, not identical.
- If you know one strand, the other can be predicted.
Example: If one strand is: 5′ – ATCGGCTA – 3′ Then the complementary strand is: 3′ – TAGCCGAT – 5′
🧠 Importance: This complementarity is the basis for:
- DNA Replication
- Transcription
- DNA Fingerprinting
- PCR amplification
Visit:
DNA DOUBLE HELIX 3D BY PERSUEAI unknown link🔁 Summary of Key Terminologies
📌 Application-Based Questions (For NEET & JENPAS)
- Why is DNA more stable than RNA? → Absence of 2'-OH group, double-stranded nature, use of thymine.
- If a DNA molecule has 20% cytosine, what is the % of adenine? → Cytosine = Guanine = 20%, So A + T = 60%, ⇒ A = 30%
- Which base pairs are stronger? → G–C (3 hydrogen bonds) are stronger than A–T (2 hydrogen bonds)
🧬 5.2 THE SEARCH FOR GENETIC MATERIAL
🧪 Step-by-Step Experimental Proofs that DNA is Genetic Material
🔬 1. Griffith’s Transformation Experiment (1928)
🧠 Objective: To determine if a chemical substance from dead bacteria could transform living bacteria.
🔍 Bacteria Used: Streptococcus pneumoniae (causes pneumonia)
- S strain (Smooth): Has polysaccharide capsule → virulent
- R strain (Rough): No capsule → non-virulent
🔬 Experimental Steps:
🔍 Interpretation:
- Some "transforming principle" from dead S strain converted R strain into S strain
- Demonstrated transfer of genetic material without knowing its exact nature
📝 Conclusion: ✅ Transformation is real and inheritable. ❗The chemical identity (DNA, RNA, or protein?) was still unknown.
🔬 2. Avery, MacLeod, McCarty Experiment (1944)
🧠 Objective: To identify the chemical nature of Griffith’s “transforming principle”
🔬 Method:
- Extracted biomolecules (DNA, RNA, proteins) from heat-killed S strain
- Treated them with specific enzymes to isolate effects:
- Protease → Destroys proteins
- RNase → Destroys RNA
- DNase → Destroys DNA
- Mixed each treated extract with live R strain and injected into mice
📊 Observations:
📝 Conclusion: ✅ Only DNA destruction blocked transformation ✅ DNA is the hereditary substance, not proteins or RNA Significance: First biochemical proof that DNA is the genetic material, not widely accepted immediately due to protein-bias in science at the time.
🔬 3. Hershey–Chase Experiment (1952)
🧠 Objective: To confirm whether DNA or protein is transferred by viruses into host cells.
🔬 Organisms Used: Bacteriophage T2 (a virus that infects E. coli)
Components of virus:
- DNA (contains phosphorus)
- Protein coat (contains sulfur)
🔬 Experiment Setup:
🧫 Procedure:
- Grow two batches of phage:
- One with ³²P (labels DNA)
- One with ³⁵S (labels protein)
- Allow each phage type to infect E. coli
- Use blender to separate viral coats from infected bacteria
- Centrifuge the solution
- Bacterial pellet = host cell content
- Supernatant = viral protein coats
- Measure radioactivity in each layer
🔍 Observations:
📝 Conclusion: ✅ Only DNA enters host and directs viral replication ✅ Final conclusive proof that DNA is the genetic material
🧬 5.3 – The RNA World
🎯 Target Exams: NEET UG | JENPAS UG | CBSE/WBCHSE Boards
🎯 Learning Objectives:
By the end of this section, learners should be able to:
- Understand the concept of the RNA World Hypothesis
- Explain why RNA was likely the first genetic material
- Describe the dual functions of RNA: genetic storage and catalysis
- Realize the evolutionary transition from RNA to DNA and proteins
- Understand the role of ribozymes and modern RNA examples
🧠 Core Concept: What is the RNA World Hypothesis?
RNA World Hypothesis proposes that early life forms on Earth may have relied solely on RNA to:
- Store genetic information
- Catalyze biochemical reactions
🌍 Hypothesis Background:
- Proposed in the 1960s and expanded by Walter Gilbert in 1986.
- Originated from studies on self-replicating RNA molecules.
🔎 Scientific Basis: Why is RNA believed to be the first genetic material?
🧪 Evidence Supporting RNA World
🔹 1. Ribozymes
- Definition: Catalytic RNA molecules that act like enzymes
- First discovered by Thomas Cech and Sidney Altman
- Capable of:
- Cutting/joining RNA
- Peptide bond formation (as in rRNA of ribosomes)
🧠 NEET Alert: Large rRNA (23S in prokaryotes; 28S in eukaryotes) acts as ribozyme in protein synthesis.
🔹 2. Self-Replication Ability
- Laboratory experiments (e.g., Spiegelman’s Monster, in vitro evolution)
- Show RNA strands can replicate and evolve under appropriate conditions
🔹 3. Viroids: Natural Proof of RNA’s Capability
- Viroids are infectious RNA molecules found in plants
- Lack protein coat, yet replicate independently
- Use host machinery, but do not require DNA or protein
📌 Example: Potato spindle tuber viroid
🔹 4. RNA in Modern Biology – A Living Fossil
🧠 These show RNA’s versatility and ancient origin.
⚖️ RNA vs DNA vs Protein in Early Life
🔁 Transition from RNA World → DNA-Protein World
Hypothesized Sequence:
- RNA molecules emerged from prebiotic soup
- Self-replicating RNA evolved
- Catalytic RNAs (ribozymes) enabled complex reactions
- Proteins took over catalytic roles (more efficient)
- DNA evolved as a stable genetic storehouse (double-stranded, proofreading)
🧠 Mnemonic: “R → R/P → P → D” RNA → RNA/Protein → Protein → DNA
🧬 Evolutionary Advantage of DNA:
📌 Thymine in DNA (instead of Uracil) further reduces mutation by detecting deamination of cytosine → uracil
📚 Summary of Key Concepts
🧪 Important Questions – NEET & JENPAS Pattern
- Which of the following molecules is both catalytic and genetic in early life? a) DNA b) Protein c) RNA d) Lipid
- The RNA molecule that acts as an enzyme is called: a) Viroid b) Ribozyme c) SnRNA d) Ribosome
- Which RNA acts as ribozyme in protein synthesis? a) mRNA b) tRNA c) 23S rRNA d) 16S rRNA
- RNA is believed to be the first genetic material because it can: a) Mutate b) Replicate c) Catalyse reactions d) All of these
🧠 Concept Map (Visual Summary)
🧬 Enzymes & Proteins Involved in DNA Replication
🧠 In prokaryotes: DNA Polymerase III = main synthesizing enzyme
DNA Polymerase I = fills in primer gaps + proofreads
🔄 Leading vs Lagging Strand
🧠 Okazaki Fragments: Short fragments (~1000–2000 bp in prokaryotes) formed during lagging strand synthesis
🔂 Direction of Replication
- DNA is antiparallel, so:
- Replication moves 5′ → 3′
- Template strand read 3′ → 5′
- Replication fork proceeds bidirectionally in prokaryotes
🧠 NEET Tip: DNA polymerase cannot initiate synthesis → needs RNA primer to begin
📊 DNA Replication in Prokaryotes vs Eukaryotes
🧬 Summary Diagram: DNA Replication Fork
5' ——————————————→ 3' (leading strand) | | Helicase DNA pol III | | 3' ————————————→ 5' ←————————— 5' (lagging strand; Okazaki fragments) ↑ RNA Primer
(Draw an annotated fork showing helicase, primase, polymerases, ligase)
🧾 Key Characteristics of DNA Polymerase:
- Adds nucleotides only in 5′ → 3′ direction
- Requires:
- Template strand
- RNA primer
- Free 3′ OH group
- Has proofreading (3′ → 5′ exonuclease) activity for error correction
🧠 Error rate: ~1 in 10⁷ base insertions; further reduced by proofreading
✅ Summary Table – DNA Replication at a Glance
📚 Practice Questions – NEET/JENPAS Style
- Which enzyme joins Okazaki fragments? a) DNA pol I b) Ligase c) Helicase d) Primase
- DNA replication is termed ‘semiconservative’ because: a) New DNA contains two new strands b) One strand is old, one is new c) One is DNA, one is RNA d) Both strands are new
- Which of the following has exonuclease activity (proofreading)? a) DNA pol III b) DNA pol I c) Both d) None
- Why does lagging strand synthesis need multiple primers? → Because it is synthesized discontinuously as Okazaki fragments
🧠 Memory Aids and Mnemonics
🧠 "He Took Pretty Long Slides"
- Helicase – Unwinds
- Topoisomerase – Releases supercoiling
- Primase – Synthesizes primers
- Ligase – Joins fragments
- SSBPs – Stabilize strands