Molecular Basis of Inheritance

Key Concepts

The DNA (Deoxyribonucleic Acid)

DNA is a long polymer of deoxyribonucleotides.

Structure of Polynucleotide Chain:
- Nucleotide: Composed of a nitrogenous base (Purines: A, G; Pyrimidines: C, T/U), a pentose sugar (Deoxyribose/Ribose), and a phosphate group.
- Linkages: N-glycosidic linkage (base to sugar), Phosphoester linkage (phosphate to sugar), and 3'-5' phosphodiester linkage (joining nucleotides).
Double Helix Model (Watson and Crick, 1953):
- Two polynucleotide chains with anti-parallel polarity (5'→3' and 3'→5').
- Bases pair via H-bonds: A=T (2 bonds), G≡C (3 bonds).
- Right-handed coiling; pitch = 3.4 nm; 10 bp per turn.

Chargaff's Rule For a double-stranded DNA, the ratio between Adenine and Thymine, and Guanine and Cytosine are constant and equal one (A+G = T+C).

Packaging of DNA:
- Prokaryotes: DNA held by positive proteins in a 'nucleoid'.
- Eukaryotes: DNA wraps around a histone octamer (rich in lysine and arginine) to form a nucleosome (200 bp).
- Chromatin: 'Beads-on-string' structure. Euchromatin (loose, active) and Heterochromatin (dense, inactive).

The Search for Genetic Material

Transforming Principle (Griffith, 1928): Observed transformation of R-strain Streptococcus pneumoniae into virulent S-strain when mixed with heat-killed S-strain.
Biochemical Characterisation (Avery, MacLeod, McCarty): Proved DNA is the transforming substance.
Hershey-Chase Experiment (1952): Unequivocal proof using radioactive isotopes (32P for DNA, 35S for protein) in bacteriophages; DNA entered the bacteria, not protein.

RNA World

RNA was the first genetic material.
Functions as a messenger, adapter, and catalyst (ribozymes).
DNA evolved from RNA for better stability.

DNA Replication

Semiconservative Mode: Proposed by Watson and Crick; experimentally proven by Meselson and Stahl (1958) using 15N isotope in E. coli.
Enzymes:
- DNA Polymerase: Synthesizes new strands in 5'→3' direction.
- Helicase: Unwinds DNA.
- DNA Ligase: Joins Okazaki fragments on the lagging strand.
Replication Fork: Site of active replication. One strand is continuous (leading), the other discontinuous (lagging).

Transcription

Process of copying genetic information from DNA to RNA.

Central Dogma of Molecular Biology Proposed by Francis Crick, it states that genetic information flows from DNA → RNA → Protein.

Transcription Unit: Promoter, Structural gene, and Terminator.
Strands: Template strand (3'→5') and Coding strand (5'→3').
Processing (Eukaryotes): Splicing (removing introns), Capping (5'-end), and Tailing (3'-end).

Genetic Code

Triplet Codon: 64 codons total; 61 code for amino acids, 3 are stop codons (UAA, UAG, UGA).
Features: Degenerate (many codons for one amino acid), Universal, Non-overlapping, and AUG (dual role: Methionine and Initiator).

Translation

Process of protein synthesis.

Charging of tRNA: Aminoacylation using ATP.
Ribosome: The cellular factory for protein synthesis.
Steps: Initiation (AUG recognized), Elongation (peptide bond formation), and Termination (release factor).

Regulation of Gene Expression

Lac Operon (Jacob and Monod):
- Regulatory Gene (i): Codes for repressor.
- Structural Genes: z (β-gal), y (permease), a (transacetylase).
- Inducer: Lactose (inactivates the repressor).

Lac Operon: Inducer Lactose acts as the inducer in the lac operon. In its presence, the repressor is inactivated, allowing RNA polymerase access to the promoter.

Negative Regulation: Repressor protein prevents transcription.

Human Genome Project (HGP)

Launched in 1990, completed in 2003.
Goals: Sequence 3 billion bp, identify ~20,000-25,000 genes, and address ELSI.
Findings: Genome has 3164.7 million bp; < 2% codes for proteins; SNP (1.4 million locations).

DNA Fingerprinting

Technique to identify variations at the DNA level using Polymorphism.
Uses VNTR (Variable Number of Tandem Repeats) as probes.
Steps: Isolation, Digestion, Electrophoresis, Blotting, Hybridization, and Autoradiography.

Molecular Basis of Inheritance

Key Concepts

The DNA (Deoxyribonucleic Acid)

DNA is a long polymer of deoxyribonucleotides.

Structure of Polynucleotide Chain:
- Nucleotide: Composed of a nitrogenous base (Purines: A, G; Pyrimidines: C, T/U), a pentose sugar (Deoxyribose/Ribose), and a phosphate group.
- Linkages: N-glycosidic linkage (base to sugar), Phosphoester linkage (phosphate to sugar), and 3'-5' phosphodiester linkage (joining nucleotides).
Double Helix Model (Watson and Crick, 1953):
- Two polynucleotide chains with anti-parallel polarity (5'→3' and 3'→5').
- Bases pair via H-bonds: A=T (2 bonds), G≡C (3 bonds).
- Right-handed coiling; pitch = 3.4 nm; 10 bp per turn.

Chargaff's Rule For a double-stranded DNA, the ratio between Adenine and Thymine, and Guanine and Cytosine are constant and equal one (A+G = T+C).

Packaging of DNA:
- Prokaryotes: DNA held by positive proteins in a 'nucleoid'.
- Eukaryotes: DNA wraps around a histone octamer (rich in lysine and arginine) to form a nucleosome (200 bp).
- Chromatin: 'Beads-on-string' structure. Euchromatin (loose, active) and Heterochromatin (dense, inactive).

The Search for Genetic Material

Transforming Principle (Griffith, 1928): Observed transformation of R-strain Streptococcus pneumoniae into virulent S-strain when mixed with heat-killed S-strain.
Biochemical Characterisation (Avery, MacLeod, McCarty): Proved DNA is the transforming substance.
Hershey-Chase Experiment (1952): Unequivocal proof using radioactive isotopes (32P for DNA, 35S for protein) in bacteriophages; DNA entered the bacteria, not protein.

RNA World

RNA was the first genetic material.
Functions as a messenger, adapter, and catalyst (ribozymes).
DNA evolved from RNA for better stability.

DNA Replication

Semiconservative Mode: Proposed by Watson and Crick; experimentally proven by Meselson and Stahl (1958) using 15N isotope in E. coli.
Enzymes:
- DNA Polymerase: Synthesizes new strands in 5'→3' direction.
- Helicase: Unwinds DNA.
- DNA Ligase: Joins Okazaki fragments on the lagging strand.
Replication Fork: Site of active replication. One strand is continuous (leading), the other discontinuous (lagging).

Transcription

Process of copying genetic information from DNA to RNA.

Central Dogma of Molecular Biology Proposed by Francis Crick, it states that genetic information flows from DNA → RNA → Protein.

Transcription Unit: Promoter, Structural gene, and Terminator.
Strands: Template strand (3'→5') and Coding strand (5'→3').
Processing (Eukaryotes): Splicing (removing introns), Capping (5'-end), and Tailing (3'-end).

Genetic Code

Triplet Codon: 64 codons total; 61 code for amino acids, 3 are stop codons (UAA, UAG, UGA).
Features: Degenerate (many codons for one amino acid), Universal, Non-overlapping, and AUG (dual role: Methionine and Initiator).

Translation

Process of protein synthesis.

Charging of tRNA: Aminoacylation using ATP.
Ribosome: The cellular factory for protein synthesis.
Steps: Initiation (AUG recognized), Elongation (peptide bond formation), and Termination (release factor).

Regulation of Gene Expression

Lac Operon (Jacob and Monod):
- Regulatory Gene (i): Codes for repressor.
- Structural Genes: z (β-gal), y (permease), a (transacetylase).
- Inducer: Lactose (inactivates the repressor).

Lac Operon: Inducer Lactose acts as the inducer in the lac operon. In its presence, the repressor is inactivated, allowing RNA polymerase access to the promoter.

Negative Regulation: Repressor protein prevents transcription.

Human Genome Project (HGP)

Launched in 1990, completed in 2003.
Goals: Sequence 3 billion bp, identify ~20,000-25,000 genes, and address ELSI.
Findings: Genome has 3164.7 million bp; < 2% codes for proteins; SNP (1.4 million locations).

DNA Fingerprinting

Technique to identify variations at the DNA level using Polymorphism.
Uses VNTR (Variable Number of Tandem Repeats) as probes.
Steps: Isolation, Digestion, Electrophoresis, Blotting, Hybridization, and Autoradiography.

Molecular Basis of Inheritance

Molecular Basis of Inheritance

Key Concepts

The DNA (Deoxyribonucleic Acid)

The Search for Genetic Material

RNA World

DNA Replication

Transcription

Genetic Code

Translation

Regulation of Gene Expression

Human Genome Project (HGP)

DNA Fingerprinting

On this page

Molecular Basis of Inheritance

Molecular Basis of Inheritance

Key Concepts

The DNA (Deoxyribonucleic Acid)

The Search for Genetic Material

RNA World

DNA Replication

Transcription

Genetic Code

Translation

Regulation of Gene Expression

Human Genome Project (HGP)

DNA Fingerprinting

On this page