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Molecular Basis Of Inheritance

Molecular Basis of Inheritance - Complete NEET Guide with Diagrams & Practice Questions

Table of Contents

  1. Introduction
  2. Key Concepts
  3. Important Formulas & Equations
  4. Memory Techniques (Mnemonics)
  5. Previous Year Questions (NEET)
  6. Key Takeaways for Quick Revision

Introduction

The "Molecular Basis of Inheritance" is arguably one of the most important and high-weightage chapters in the entire NEET Biology syllabus. Building upon the principles laid down by Mendel, this chapter delves into the very substance of life—DNA. It answers fundamental questions: What is the genetic material? How does it copy itself? How does it control the traits of an organism?

For NEET, a deep and clear understanding of DNA structure, replication, transcription, and translation is non-negotiable. This chapter, combined with its preceding chapter on inheritance, forms the backbone of genetics and typically contributes 5-6 questions to the exam. Mastering the concepts, diagrams, and experimental proofs discussed here will significantly boost your score. This guide will simplify these complex molecular processes and prepare you to tackle any question with confidence.

Key Concepts

1. The DNA: Structure and Packaging

Deoxyribonucleic acid (DNA) is a long polymer of deoxyribonucleotides and is the genetic material in most organisms.

  • Structure of a Polynucleotide Chain: A nucleotide has three components:
    1. A nitrogenous base (Purines: Adenine, Guanine; Pyrimidines: Cytosine, Thymine)
    2. A pentose sugar (Deoxyribose)
    3. A phosphate group
  • Watson-Crick Double Helix Model (1953): Based on X-ray diffraction data from Maurice Wilkins and Rosalind Franklin, Watson and Crick proposed the following salient features:
    • DNA is made of two polynucleotide chains coiled in a right-handed fashion.
    • The two chains have anti-parallel polarity (one chain is 5'→3', the other is 3'→5').
    • The backbone is formed by sugar and phosphate; the bases project inwards.
    • Complementary Base Pairing: Adenine (A) pairs with Thymine (T) via two hydrogen bonds. Guanine (G) pairs with Cytosine (C) via three hydrogen bonds.
    • Chargaff's Rule: For a double-stranded DNA, the ratios A/T and G/C are equal to one (A=T, G=C).
    • The two strands are separated by a consistent distance because a purine always pairs with a pyrimidine.
    • Dimensions: Pitch of the helix is 3.4 nm with roughly 10 base pairs (bp) in each turn. The distance between two adjacent base pairs is 0.34 nm.

Figure: The Double Helix structure of DNA showing anti-parallel strands, sugar-phosphate backbone, and complementary base pairing (A=T, G≡C).

  • Packaging of DNA Helix:
    • The length of human DNA is ~2.2 meters, which must be packaged into a nucleus of ~10⁻⁶ m.
    • In Eukaryotes: This is achieved by wrapping the negatively charged DNA around a set of positively charged, basic proteins called histones.
    • Nucleosome: The structure formed by DNA wrapped around a histone octamer (eight histone molecules). A typical nucleosome contains 200 bp of DNA helix.
    • Chromatin: A thread-like structure formed by repeating units of nucleosomes, often described as "beads-on-string". Chromatin is further coiled to form chromosomes.

Figure: The Nucleosome model showing DNA wrapped around a histone octamer with H1 histone linking adjacent nucleosomes.

2. The Search for Genetic Material

The quest to determine whether DNA or protein was the genetic material involved several key experiments.

  1. Griffith's Transforming Principle (1928): Using Streptococcus pneumoniae, Griffith showed that a "transforming principle" from heat-killed virulent (S-strain) bacteria could transform non-virulent (R-strain) bacteria into the virulent form.
  2. Avery, MacLeod, and McCarty's Experiment (1933-44): They biochemically characterized the transforming principle and concluded that DNA was the genetic material, as treating the substance with DNase inhibited transformation, while proteases and RNases did not.
  3. Hershey-Chase Experiment (1952): This provided unequivocal proof. They used bacteriophages (viruses that infect bacteria) and labeled them with radioactive isotopes.
    • Batch 1: Phages grown with radioactive sulfur (³⁵S) to label proteins.
    • Batch 2: Phages grown with radioactive phosphorus (³²P) to label DNA.
    • Result: Only ³²P (DNA) was found inside the infected bacterial cells, proving that DNA is the genetic material that is passed from the virus to the bacteria.

3. DNA Replication: The Copying Mechanism

DNA replication is the process by which a DNA molecule produces two identical copies of itself. Watson and Crick proposed that it is semiconservative.

  • Semiconservative Replication: Each new DNA molecule has one parental (conserved) strand and one newly synthesized strand.
  • Meselson and Stahl's Experiment (1958): Provided experimental proof for semiconservative replication using heavy nitrogen isotope (¹⁵N) and E. coli. They showed that after one generation in a ¹⁴N medium, the DNA was of a hybrid density, and after the second generation, it was composed of equal amounts of light and hybrid DNA.

Figure: The Meselson-Stahl experiment demonstrating semiconservative replication.

  • The Replication Machinery (Enzymes):
    • Helicase: Unwinds the DNA double helix at the origin of replication, creating a replication fork.
    • DNA-dependent DNA Polymerase: The main enzyme that synthesizes the new DNA strand. It can only polymerize in the 5'→3' direction and requires a template.
    • Leading Strand: Synthesized continuously on the 3'→5' template strand.
    • Lagging Strand: Synthesized discontinuously in short fragments (called Okazaki fragments) on the 5'→3' template strand.
    • DNA Ligase: Joins the Okazaki fragments together to form a continuous strand.

4. Transcription: From DNA to RNA

Transcription is the process of copying genetic information from one strand of the DNA into RNA.

  • Transcription Unit: A segment of DNA that is transcribed. It consists of:
    1. A Promoter: The binding site for RNA polymerase, located at the 5'-end (upstream).
    2. The Structural Gene: The sequence that is transcribed.
    3. A Terminator: The site where transcription stops, located at the 3'-end (downstream).
  • Template vs. Coding Strand: Only one DNA strand, the template strand (3'→5' polarity), is transcribed. The other strand, the coding strand (5'→3' polarity), has the same sequence as the RNA (except T is replaced by U).
  • Transcription in Eukaryotes vs. Prokaryotes:
    • Prokaryotes: Have a single DNA-dependent RNA polymerase. Transcription and translation are coupled (occur simultaneously in the cytoplasm).
    • Eukaryotes: Have three RNA polymerases. The primary transcript (hnRNA) is non-functional and undergoes post-transcriptional modifications:
      1. Splicing: Removal of non-coding sequences (introns) and joining of coding sequences (exons).
      2. Capping: Addition of methyl guanosine triphosphate at the 5'-end.
      3. Tailing: Addition of 200-300 adenylate residues (poly-A tail) at the 3'-end. The fully processed hnRNA is now called mRNA and is transported to the cytoplasm for translation.

5. The Genetic Code: Life's Dictionary

The relationship between the sequence of nucleotides in mRNA and the sequence of amino acids in a protein is called the genetic code.

  • Salient Features:
    • Triplet: Each codon is composed of three nucleotides. 64 possible codons exist.
    • Specific and Unambiguous: One codon codes for only one amino acid.
    • Degenerate: Some amino acids are coded by more than one codon.
    • Contiguous: The code is read in a continuous fashion without any punctuations.
    • Nearly Universal: A specific codon codes for the same amino acid in almost all organisms.
    • Initiator Codon: AUG has a dual function. It codes for Methionine (met) and also acts as the start codon.
    • Stop (Terminator) Codons: UAA, UAG, UGA do not code for any amino acid and signal the end of translation.

6. Translation: RNA to Protein

Translation is the process of polymerization of amino acids to form a polypeptide.

  • Location: Ribosomes in the cytoplasm.
  • Requirements:
    • mRNA: Provides the template with the codons.
    • tRNA (transfer RNA): The "adapter molecule". It has an anticodon loop that is complementary to the mRNA codon and an amino acid acceptor end.
    • Ribosomes: The cellular factory for protein synthesis.
  • Steps in Translation:
    1. Charging of tRNA: Activation of amino acids and their attachment to the specific tRNA (aminoacylation).
    2. Initiation: The ribosome binds to the mRNA at the start codon (AUG).
    3. Elongation: The ribosome moves along the mRNA, codon by codon. Charged tRNAs bring in amino acids, and peptide bonds are formed between them.
    4. Termination: When the ribosome reaches a stop codon, a release factor binds, and the completed polypeptide is released.

Figure: The process of translation showing the ribosome moving along the mRNA, with tRNAs bringing in amino acids to form a polypeptide chain.

7. Regulation of Gene Expression: The Lac Operon

An operon is a functional unit of DNA containing a cluster of genes under the control of a single promoter. The lac operon, studied by Jacob and Monod, is a classic example of gene regulation in E. coli.

  • Components of the Lac Operon:
    • Regulatory Gene (i): Codes for a repressor protein.
    • Promoter (p): Binding site for RNA polymerase.
    • Operator (o): Binding site for the repressor protein.
    • Structural Genes: lacZ (codes for β-galactosidase), lacY (codes for permease), lacA (codes for transacetylase).
  • Mechanism (Negative Regulation):
    • In the absence of lactose (inducer): The repressor protein binds to the operator, blocking RNA polymerase and preventing transcription of the structural genes. The operon is switched OFF.
    • In the presence of lactose (inducer): Lactose binds to the repressor, inactivating it. The repressor can no longer bind to the operator. RNA polymerase is free to transcribe the structural genes. The operon is switched ON.

Figure: The Lac Operon shown in both the repressed (OFF) and induced (ON) states.

8. Human Genome Project (HGP) and DNA Fingerprinting

  • Human Genome Project (1990-2003): A mega project aimed at sequencing the entire human genome.
    • Key Findings: The human genome has 3164.7 million bp, ~30,000 genes, and 99.9% of the nucleotide bases are exactly the same in all people.
  • DNA Fingerprinting: A technique to identify differences in specific DNA regions called repetitive DNA.
    • Principle: It relies on polymorphism in short, repeated sequences called Variable Number of Tandem Repeats (VNTRs). The number of repeats is unique to each individual.
    • Application: Forensic science, paternity testing, and studying genetic diversity.

Important Formulas & Equations

  • Chargaff's Rule: A + G = T + C, or (A+G)/(T+C) = 1.
  • DNA Length Calculation: Length = (Total number of base pairs) × (Distance between two adjacent base pairs, i.e., 0.34 nm).
  • Codon Calculation: Total possible codons = 4ⁿ (where n = number of bases in a codon). For a triplet code, 4³ = 64 codons.

Memory Techniques (Mnemonics)

  • Purines vs. Pyrimidines:
    • Purines are Adenine and Guanine (Pure As Gold).
    • Pyrimidines are Cytosine, Thymine, Uracil (Remember: CUT the Pye).
  • Stop Codons: UAA (U Are Away), UAG (U Are Gone), UGA (U Go Away).
  • Eukaryotic RNA Polymerases and their products: Remember R-M-T for Polymerase I, II, III.
    • Pol I -> rRNA
    • Pol II -> mRNA (actually hnRNA)
    • Pol III -> tRNA (and 5S rRNA)
  • Lac Operon Structural Genes: Think "ZYA" in order.
    • Z -> β-galactosidase (breaks lactose)
    • Y -> Permease (lets lactose in)
    • A -> Transacetylase

Previous Year Questions (NEET)

Q1. If Adenine makes 30% of the DNA molecule, what will be the percentage of Thymine, Guanine and Cytosine in it? (NEET 2021) a) T: 20, G: 30, C: 20 b) T: 20, G: 20, C: 30 c) T: 30, G: 20, C: 20 d) T: 20, G: 25, C: 25

Explanation: According to Chargaff's rule, A = T and G = C. If A = 30%, then T must also be 30%. Together, A+T = 60%. The remaining 40% must be G+C. Since G=C, each must be 20%. Answer: (c) T: 30, G: 20, C: 20

Q2. The experimental proof for semiconservative replication of DNA was first shown in a: (NEET 2018) a) Plant b) Bacterium c) Fungus d) Virus

Explanation: The famous Meselson and Stahl experiment (1958) which proved the semiconservative nature of DNA replication was performed on the bacterium Escherichia coli. Answer: (b) Bacterium

Q3. The final proof for DNA as the genetic material came from the experiments of: (NEET 2017) a) Griffith b) Hershey and Chase c) Avery, MacLeod and McCarty d) Hargobind Khorana

Explanation: While Griffith's and Avery's experiments were foundational, the Hershey and Chase experiment provided the unequivocal or final proof by using radioactive isotopes to show that it was the phage DNA, not protein, that entered the host bacterium. Answer: (b) Hershey and Chase

Q4. If the sequence of nucleotides in the coding strand of a transcription unit is 5'-ATGCATGC-3', the sequence of the transcribed mRNA would be: (NEET 2022) a) 5'-UACGUACG-3' b) 3'-UACGUACG-5' c) 5'-AUGCAUGC-3' d) 3'-AUGCAUGC-5'

Explanation: The transcribed mRNA has the same sequence and polarity as the coding strand, with the only difference being that Thymine (T) is replaced by Uracil (U). Answer: (c) 5'-AUGCAUGC-3'

Key Takeaways for Quick Revision

  • DNA is a right-handed, anti-parallel double helix with complementary base pairing (A=T, G≡C).
  • DNA is the genetic material, proven by the Hershey-Chase experiment.
  • Replication is semiconservative, requiring helicase, DNA polymerase, and ligase. The synthesis is continuous on the leading strand and discontinuous (Okazaki fragments) on the lagging strand.
  • The Central Dogma is DNA → (transcription) → RNA → (translation) → Protein.
  • Transcription in eukaryotes is complex, involving splicing, capping, and tailing to convert hnRNA to mRNA.
  • The Genetic Code is triplet, degenerate, and nearly universal. AUG is the start codon, and UAA, UAG, UGA are stop codons.
  • The Lac Operon is an inducible system in E. coli where lactose acts as the inducer to switch the operon ON.
  • DNA Fingerprinting relies on VNTRs to create a unique profile for an individual.
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