Molecular Basis of Inheritance - Class 12 Boards Accountancy

Molecular Basis of Inheritance

Discovery and Structure of DNA

DNA is a long, acidic polymer present in the nucleus, first observed by Friedrich Miescher in 1869, who called it "nuclein." Altmann later identified its acidic nature. Watson and Crick, using X-ray diffraction data from Rosalind Franklin, proposed the double helical structure of DNA. The length of DNA is measured by the number of nucleotides, with human DNA being approximately 2.2 meters long.

• Key Scientists:
  • Watson: Studied bacteriophage multiplication using X-rays.
  • Crick: Co-discovered the double helix structure.
  • Rosalind Franklin: Provided X-ray diffraction data.
  • Miescher:…

Molecular Basis of Inheritance

Discovery and Structure of DNA

DNA is a long, acidic polymer present in the nucleus, first observed by Friedrich Miescher in 1869, who called it "nuclein." Altmann later identified its acidic nature. Watson and Crick, using X-ray diffraction data from Rosalind Franklin, proposed the double helical structure of DNA. The length of DNA is measured by the number of nucleotides, with human DNA being approximately 2.2 meters long.

• Key Scientists:

  • Watson: Studied bacteriophage multiplication using X-rays.
  • Crick: Co-discovered the double helix structure.
  • Rosalind Franklin: Provided X-ray diffraction data.
  • Miescher: Discovered nuclein (DNA).
  • Altmann: Identified DNA as acidic.

• DNA Length Examples:

  • E. coli: $4.6 \times 10^6$ base pairs (circular, double-stranded)
  • Human: $3.3 \times 10^9$ base pairs (linear, double-stranded)

Structure and Composition of Nucleic Acids

DNA is a polymer of nucleotides, each consisting of a sugar, a nitrogenous base, and a phosphate group. The sugar is deoxyribose in DNA and ribose in RNA. Nitrogenous bases are classified as purines (adenine, guanine) and pyrimidines (cytosine, thymine in DNA; uracil in RNA).

• Nucleotide vs Nucleoside:

  • Nucleotide: Sugar + Nitrogenous base + Phosphate
  • Nucleoside: Sugar + Nitrogenous base (no phosphate)

• Bond Types:

  • Sugar–phosphate: Phosphoester bond
  • Sugar–base: Glycosidic bond
  • Between nucleotides: Phosphodiester bond

• Purines: Double ring (A, G)

• Pyrimidines: Single ring (C, T, U)

Double Helical Structure and Features of DNA

DNA consists of two antiparallel strands with a sugar-phosphate backbone and bases pointing inward. The strands are held together by hydrogen bonds between complementary bases: A pairs with T (2 H-bonds), G pairs with C (3 H-bonds). The double helix is right-handed, with 10 base pairs per turn and a pitch of 3.4 nm.

• Key Features:

  • Two antiparallel strands: one 5'→3', one 3'→5'
  • Base pairing: A=T (2 H-bonds), G≡C (3 H-bonds)
  • One pitch = 10 base pairs = 3.4 nm; distance between adjacent base pairs = 0.34 nm
  • Stability due to base stacking and hydrogen bonding

• Chargaff’s Rule: Amount of purines equals pyrimidines ($A+G = T+C$), ratio is constant and equals one.

DNA Packaging in Prokaryotes and Eukaryotes

DNA is highly compacted to fit inside the cell. In prokaryotes, DNA is associated with non-histone proteins, forming a nucleoid. In eukaryotes, DNA wraps around positively charged histone proteins, forming nucleosomes.

• Eukaryotic Packaging:
  • Histone octamer: 2 each of H2A, H2B, H3, H4; H1 as linker
  • Nucleosome: ~200 base pairs of DNA wrapped around histone octamer
  • "Beads on string" appearance under microscope
  • Chromatin types:
    • Euchromatin: Loosely packed, transcriptionally active
    • Heterochromatin: Tightly packed, transcriptionally inactive

Replication of DNA

DNA replication is semi-conservative: each new DNA molecule has one parental and one newly synthesized strand. The process requires several enzymes and occurs during the S phase of the cell cycle.

• Key Enzymes and Steps:

  • Helicase: Unzips DNA by breaking H-bonds
  • Topoisomerase (gyrase): Prevents supercoiling
  • SSBP: Prevents reannealing of single strands
  • Primase: Synthesizes RNA primer
  • DNA polymerase III: Synthesizes new DNA (5'→3'), requires primer
  • DNA polymerase I: Proofreading and primer removal
  • DNA ligase: Joins Okazaki fragments on lagging strand

• Strands:

  • Leading strand: Synthesized continuously
  • Lagging strand: Synthesized discontinuously as Okazaki fragments

• Replication Fork: The Y-shaped region where DNA is unwound and replication occurs.

• Experimental Proof: Meselson and Stahl used $^{15}N$ and $^{14}N$ isotopes to demonstrate semi-conservative replication.

Transcription: DNA to RNA

Transcription is the synthesis of RNA from a DNA template. Only one DNA strand (template strand) is transcribed. The coding strand has the same sequence as the RNA (except T is replaced by U).

• Transcription Unit:

  • Promoter: Initiation site
  • Structural gene: Coding region
  • Terminator: End site

• Types of RNA:

  • mRNA: Messenger RNA (by RNA polymerase II)
  • tRNA: Transfer RNA (by RNA polymerase III)
  • rRNA: Ribosomal RNA (by RNA polymerase I)

• Prokaryotes:

  • Single RNA polymerase synthesizes all RNAs
  • Sigma factor: Initiation
  • Rho factor: Termination
  • Transcription and translation occur in cytoplasm, often simultaneously

• Eukaryotes:

  • Three RNA polymerases
  • Transcription in nucleus, translation in cytoplasm
  • mRNA processing: 5' capping (methyl guanosine triphosphate), splicing (removal of introns), 3' polyadenylation (poly-A tail)

Genetic Code and Mutations

The genetic code is a set of triplet codons on mRNA that specify amino acids. There are 64 codons: 61 code for amino acids, 3 are stop codons (UAA, UAG, UGA). AUG codes for methionine and acts as the start codon.

• Features:

  • Triplet, non-overlapping, comma-less, nearly universal
  • Degeneracy: Multiple codons for one amino acid (e.g., UUU and UUC for phenylalanine)
  • Start codon: AUG (methionine)
  • Stop codons: UAA, UAG, UGA

• Mutations:

  • Point mutation: Single base change (e.g., GAG to GTG in sickle cell anemia)
  • Frameshift mutation: Insertion or deletion shifts reading frame

Translation: Protein Synthesis

Translation is the process of synthesizing proteins from mRNA using ribosomes, tRNA, and amino acids. It occurs in the cytoplasm and involves four main steps.

• Steps:

  1. Activation of amino acids and charging of tRNA (aminoacyl-tRNA synthetase, ATP required)
  2. Initiation: Small ribosomal subunit binds mRNA, initiator tRNA binds to P site, large subunit joins
  3. Elongation: tRNAs bring amino acids to A site, peptide bond forms (catalyzed by 23S rRNA/ribozyme), ribosome shifts, empty tRNA exits via E site
  4. Termination: Stop codon reached, release factor binds, polypeptide released

• Sites on Ribosome:

  • A (Aminoacyl) site: Entry of charged tRNA
  • P (Peptidyl) site: Peptide bond formation
  • E (Exit) site: tRNA exit

• tRNA Structure:

  • Cloverleaf (2D), L-shaped (3D)
  • Five arms: Amino acid binding arm, TψC arm, anticodon arm, DHU arm, variable arm

Regulation of Gene Expression: Lac Operon

Gene expression can be regulated by switching genes on or off as needed. The lac operon in prokaryotes is a classic example of negative regulation, controlled by the presence or absence of lactose.

• Lac Operon Components:

  • I: Regulatory gene (produces repressor)
  • P: Promoter (binding site for RNA polymerase)
  • O: Operator (binding site for repressor)
  • Z, Y, A: Structural genes (β-galactosidase, permease, transacetylase)
  • Inducer: Lactose

• Mechanism:

  • No lactose: Repressor binds operator, transcription off
  • Lactose present: Inducer binds repressor, repressor inactivated, transcription on

• Lac operon is inducible and a catabolic operon.

Human Genome Project and DNA Fingerprinting

The Human Genome Project aimed to sequence all human DNA, identifying 3.1647 billion base pairs and about 30,000 genes. Less than 2% of the genome codes for proteins. Chromosome 1 has the most genes, Y the fewest.

• Key Points:

  • Initiated in 1990, completed in 2003 (except chromosome 1, completed in 2006)
  • Used yeast and bacterial artificial chromosomes as vectors
  • Two approaches: Expressed Sequence Tags (ESTs) for coding regions, Sequence Annotation for whole genome

• DNA Fingerprinting:

  • Technique to identify individuals based on unique DNA patterns
  • Uses repetitive DNA sequences (VNTRs, minisatellites, microsatellites)
  • Steps: DNA extraction, PCR amplification, restriction digestion, gel electrophoresis, Southern blotting, probe hybridization, X-ray detection
  • Applications: Forensics, paternity testing, population genetics

• Salient Features:

  • 99.9% of human DNA is identical; 0.1% accounts for individual differences
  • Satellite DNA shows high degree of polymorphism, useful for identification

• Ethical, Legal, Social Issues (ELSI): Addressed due to sensitive nature of genetic information.