📝 Chapter Notes & Revision

Molecular Basis of Inheritance

🏫 MP BoardClass 12Biology

📐 Formula & Cheat Sheet (English)

Quick Revision Notes & Formula Sheet

Class: 12th Biology
Chapter: Molecular Basis of Inheritance (आनुवंशिकையின் आणविक आधार)

### 1. Introduction & Genetic Material

  • DNA (Deoxyribonucleic Acid): The predominant genetic material in most organisms. It is a long polymer of deoxyribonucleotides.
  • RNA (Ribonucleic Acid): Acts as a genetic material in some viruses (e.g., Q-beta bacteriophage, Tobacco Mosaic Virus). Primarily functions as a messenger, adaptor, and structural molecule.
  • Central Dogma of Molecular Biology: Proposed by Francis Crick. It states the flow of genetic information: Replication $\rightarrow$ DNA $\xrightarrow{\text{Transcription}}$ mRNA $\xrightarrow{\text{Translation}}$ Protein

### 2. Structure of Polynucleotide Chain (DNA & RNA)

  • Nucleotide Components:
    1. Nitrogenous Base (Purines: Adenine, Guanine; Pyrimidines: Cytosine, Thymine [Uracil in RNA])
    2. Pentose Sugar (Deoxyribose in DNA, Ribose in RNA)
    3. Phosphate Group ($PO_4^{3-}$)
  • Nucleoside = Nitrogenous Base + Pentose Sugar
  • Nucleotide = Nucleoside + Phosphate Group (linked by Phosphoester bond)
  • Linkages:
    • N-glycosidic linkage: Between nitrogenous base and 1' C of sugar.
    • Phosphodiester bond: Joins two nucleotides at 3' and 5' carbon atoms, forming the backbone.

### 3. Watson and Crick Model of DNA Double Helix

  • Composed of two polynucleotide chains where the backbone is constituted by sugar-phosphate, and the bases project inside.
  • The two chains have antiparallel polarity (one runs $5' \rightarrow 3'$ and the other $3' \rightarrow 5'$).
  • The bases are paired through Hydrogen bonds ($A=T$ with 2 H-bonds, $G \equiv C$ with 3 H-bonds), making it complementary.
  • Erwin Chargaff's Rule: In double-stranded DNA, the ratio between Adenine and Thymine, and Guanine and Cytosine is constant and equals one. [A] + [G] = [T] + [C] or [A] = [T] and [G] = [C]
  • Dimensions of B-DNA:
    • Pitch of helix = $3.4\text{ nm}$ ($34\text{ \AA}$)
    • Number of base pairs per turn = $10$
    • Distance between adjacent base pairs = $0.34\text{ nm}$ ($3.4\text{ \AA}$)

### 4. Packaging of DNA Helix

  • Distance between consecutive base pairs: $0.34\text{ nm}$ ($0.34 \times 10^{-9}\text{ m}$).
  • Total length of DNA in a human cell: $\approx 2.2\text{ meters}$ (Calculated as: Total bp $\times$ distance between two bp $= 6.6 \times 10^9 \text{ bp} \times 0.34 \times 10^{-9}\text{ m/bp}$).
  • Packaging in Eukaryotes: DNA is negatively charged and is wrapped around positively charged histone octamer (proteins rich in basic amino acids lysine and arginine) to form a structure called Nucleosome.
    • A typical nucleosome contains 200 bp of DNA helix.
    • Nucleosomes repeat to form Chromatin ("beads-on-string" structure), which further condenses to form Chromosomes at metaphase.
  • Euchromatin: Loosely packed chromatin, transcriptionally active.
  • Heterochromatin: Densely packed chromatin, transcriptionally inactive.

### 5. The Search for Genetic Material

  • Griffith’s Transformation Experiment (1928): Using Streptococcus pneumoniae and mice, proved that something from heat-killed smooth (S) strain transformed live rough (R) strain into virulent S strain.
  • Biochemical Characterization (Avery, MacLeod, and McCarty, 1944): Proved that DNA is the hereditary material (Proteases and RNases did not affect transformation, but DNase did).
  • Hershey-Chase Experiment (1952): Used bacteriophages and radioactive isotopes ($^{32}P$ and $^{35}S$) to unequivocally prove that DNA is the genetic material, not protein.

### 6. Replication of DNA

  • Semiconservative Replication: Proposed by Watson and Crick; experimentally proved by Meselson and Stahl (1958) using $^{15}N$ isotope in E. coli and Taylor et al. (1958) using Vicia faba (faba beans) with radioactive thymidine.
  • Key Enzyme: DNA-dependent DNA Polymerase.
  • Important Rules for Replication:
    • Replication occurs in the $5' \rightarrow 3'$ direction.
    • Leading Strand: Continuous replication towards the replication fork.
    • Lagging Strand: Discontinuous replication away from the replication fork, forming Okazaki fragments which are later joined by DNA Ligase.
    • Requires an RNA primer to initiate.

### 7. Transcription (DNA to RNA)

  • The process of copying genetic information from one strand of DNA into RNA.
  • Transcription Unit: Consists of three regions:
    1. Promoter (प्रमोटर)
    2. Structural Gene (संरचनात्मक जीन)
    3. Terminator (समापक)
  • Template Strand: The DNA strand with $3' \rightarrow 5'$ polarity acts as a template.
  • Coding Strand: The DNA strand with $5' \rightarrow 3'$ polarity (does not code for anything, same sequence as RNA except Thymine is replaced by Uracil).
  • Enzyme: DNA-dependent RNA Polymerase.
  • Post-Transcriptional Modifications (in Eukaryotes):
    1. Capping: An unusual nucleotide (methyl guanosine triphosphate) is added to the 5' end of hnRNA.
    2. Tailing: Adenylate residues (200-300) are added at the 3' end.
    3. Splicing: Removal of introns (non-coding sequences) and joining of exons (coding sequences) in a defined order.

### 8. Genetic Code

  • The relationship between the sequence of amino acids in a polypeptide and nucleotide triplet sequence in mRNA.
  • Salient Features:
    1. Triplet codon: 64 codons in total (61 code for amino acids, 3 are stop codons).
    2. Degenerate: Some amino acids are coded by more than one codon.
    3. Unambiguous: One codon specifies only one specific amino acid.
    4. Universal: A codon specifies the same amino acid from bacteria to humans (few exceptions).
    5. Commaless: Read in a contiguous fashion without punctuation.
    6. Initiator Codon: AUG (Codes for Methionine).
    7. Stop Codons: UAA, UAG, UGA (do not code for any amino acid).

### 9. Translation (Protein Synthesis)

  • The polymerization of amino acids to form a polypeptide, guided by the sequence of codons on mRNA.
  • Steps:
    1. Activation of Amino acids: Amino acids are activated in the presence of ATP and linked to their cognate tRNA (charging of tRNA / aminoacylation).
    2. Initiation: Ribosome binds to mRNA at the start codon (AUG).
    3. Elongation: Ribosome moves along mRNA codon by codon, and peptide bonds are formed between sequential amino acids using peptidyl transferase.
    4. Termination: Release factor binds to the stop codon, terminating translation and releasing the complete polypeptide.

### 10. Regulation of Gene Expression

  • Regulation occurs at various levels in eukaryotes (transcriptional, processing, transport, translational).
  • The Lac Operon (Jacob and Monod): An inducible operon system in E. coli for lactose metabolism.
    • Components:
      • Regulator gene ($i$ code): Produces the repressor protein.
      • Promoter gene ($p$): Binding site for RNA polymerase.
      • Operator gene ($o$): Binding site for repressor protein.
      • Structural genes:
        • z gene: Encodes $\beta$-galactosidase (breaks lactose into glucose and galactose).
        • y gene: Encodes permease (increases permeability to $\beta$-galactosidase).
        • a gene: Encodes transacetylase.
    • In absence of inducer (Lactose absent): Repressor binds to the operator, blocking RNA polymerase; operon is switched off.
    • In presence of inducer (Lactose present): Lactose acts as an inducer, binds to the repressor, inactivating it. RNA polymerase transcribes the structural genes; operon is switched on.

### 11. Human Genome Project (HGP)

  • Mega project launched in 1990 and completed in 2003.
  • Key Goals: Identify all genes ($\approx 30,000$), determine sequences of 3 billion chemical base pairs in human DNA.
  • Salient Features of Human Genome:
    • Contains $3.1647 \times 10^9$ nucleotide bases.
    • Average gene consists of 3,000 bases, but sizes vary greatly (Dystrophin is largest with 2.4 million bases).
    • Total number of genes is estimated at 30,000 (much lower than previous estimates).
    • Less than $2%$ of the genome codes for proteins.
    • Repeated sequences make up a very large portion of the human genome.
    • Chromosome 1 has most genes (2968), and Y has the fewest (231).
    • Scientists have identified about 1.4 million locations where single base DNA differences (SNPs - Single Nucleotide Polymorphisms) occur in humans.

### 12. DNA Fingerprinting

  • Technique developed by Alec Jeffreys to identify individuals based on DNA sequence differences.
  • Principle: Focuses on VNTRs (Variable Number of Tandem Repeats)—short nucleotide repeats that show high degree of polymorphism (vary from person to person).
  • Steps in DNA Fingerprinting:
    1. Isolation of DNA.
    2. Digestion of DNA by restriction endonucleases.
    3. Separation of DNA fragments by agarose gel electrophoresis.
    4. Blotting (transferring separated fragments to nitrocellulose or nylon membrane).
    5. Hybridization using labelled VNTR probe.
    6. Detection of hybridizing fragments by autoradiography.
  • Applications: Forensic science, resolving parentage disputes, determining population genetics and biodiversity.