Molecular Basis of Inheritance
1. Introduction
The molecular basis of inheritance explains how DNA stores, replicates, and expresses genetic information. This chapter covers the central dogma of molecular biology: DNA → RNA → Protein.
2. DNA Structure
2.1 Watson-Crick Model
Double helix with two antiparallel strands. The sugar-phosphate backbone is on the outside and the nitrogenous bases are on the inside.
Base pairing: A = T (2 hydrogen bonds), G ≡ C (3 hydrogen bonds).
2.2 Components
Nucleotide: Deoxyribose sugar + phosphate + nitrogenous base (A, G, C, T).
2.3 Chargaff's Rule
% A = % T, % G = % C. Purines = Pyrimidines.
3. DNA Replication
3.1 Semiconservative Replication
Each daughter DNA molecule has one parental strand and one newly synthesized strand. Demonstrated by Meselson and Stahl using ¹⁵N labeling.
3.2 Enzymes Involved
Helicase: Unwinds DNA. DNA polymerase: Adds nucleotides in 5' → 3' direction. Primase: Synthesizes RNA primers. Ligase: Joins Okazaki fragments (on lagging strand). Topoisomerase: Relieves supercoiling.
3.3 Leading and Lagging Strands
Leading strand: Continuous synthesis. Lagging strand: Discontinuous synthesis (Okazaki fragments).
4. Transcription
DNA → RNA. Occurs in the nucleus (eukaryotes).
RNA polymerase: In prokaryotes, one enzyme. In eukaryotes, three types (RNA pol I, II, III).
Steps: Initiation (promoter binding) → Elongation → Termination.
Processing of hnRNA: Capping (5' end), Polyadenylation (3' end), Splicing (removal of introns).
5. Genetic Code
Triplet codons that specify amino acids. 64 codons (61 code for amino acids, 3 are stop codons).
Features: Triplet, degenerate, universal, non-overlapping, commaless.
6. Translation (RNA → Protein)
Ribosomes: Site of protein synthesis. mRNA is read 5' → 3'.
tRNA: Adapter molecule with anticodon. Charged with amino acid (aminoacylation).
Steps: Initiation (ribosome assembly, AUG start codon) → Elongation (peptide bond formation) → Termination (stop codon, release factor).
7. Regulation of Gene Expression
Lac operon: E. coli gene regulation.
- Structural genes: lacZ, lacY, lacA.
- Regulator gene: lacI (produces repressor).
- Inducer: Allolactose (inactivates repressor).
When lactose is present: Repressor is inactivated, operon is expressed. When lactose is absent: Repressor binds to operator, operon is repressed.
8. Human Genome Project (HGP)
Goal: Sequence the entire human genome (~3 billion base pairs). Completed in 2003.
Findings: ~20,000-25,000 genes. 99.9% identical between individuals. Only ~1.5% codes for proteins.
9. DNA Fingerprinting
A technique to identify individuals based on their DNA sequences, especially variable number tandem repeats (VNTRs).
Applications: Forensics (crime scene), paternity testing, identification of remains.
10. Worked Problems
Problem 1: A DNA strand has sequence 5'-ATGCCTAG-3'. Write the complementary strand. Solution: 3'-TACGGATC-5'.
11. Common Mistakes
'Students often confuse replication and transcription. Replication makes DNA from DNA (both strands). Transcription makes RNA from DNA (one strand).'
12. ISC Exam Focus
| Topic | Theory Marks | Practical Marks |
|---|---|---|
| DNA structure and replication | 4 | 2 |
| Transcription and translation | 4 | 2 |
| Genetic code | 3 | 1 |
| HGP and fingerprinting | 3 | 2 |
13. Self-Test Questions
- Describe the Watson-Crick model of DNA structure.
- Explain the mechanism of DNA replication. What is the role of Okazaki fragments?
- How is the genetic code degenerate and universal? Explain with examples.
- Describe the structure and function of the lac operon.
- What is DNA fingerprinting? Describe its steps and applications.
