Detailed Notes Chapter 5-Molecular Basis Of Inheritance

Chapter 5-Molecular Basis Of Inheritance

Introduction

Inheritance Patterns and Genetic Basis:
- Previous chapter covered inheritance patterns and genetic basis.
- Mendel’s time lacked clarity on factors regulating inheritance.
Discovery of DNA as Genetic Material:
- Over the next century, investigation led to DNA as primary genetic material.
- DNA (deoxyribonucleic acid) is predominant genetic material in most organisms.
Types of Nucleic Acids:
- Nucleic acids are polymers of nucleotides.
- Two main types: DNA and RNA (ribonucleic acid).
Functions of DNA and RNA:
- DNA primarily genetic material; RNA acts as messenger in most cases.
- RNA has additional roles as adapter, structural, and sometimes catalytic molecule.
Structure of Nucleotides and Nucleic Acid Polymers:
- Nucleotide structures and their polymerization into nucleic acids taught in Class XI.
Topics Covered in the Chapter:
- Structure of DNA, its replication, transcription, genetic code, protein synthesis, and basic genetic regulation.
Human Genome Sequencing:
- Completion of human genome sequence marked new era in genomics.
- Consequences of genome sequencing to be discussed.
Introduction to DNA Structure:
- Chapter begins by understanding DNA’s structure, deemed most intriguing molecule in living systems.
Future Sections:
- Further exploration into DNA’s abundance as genetic material and its relationship with RNA.

5.1 THE DNA

DNA Composition:
- DNA is composed of long polymers of deoxyribonucleotides.
Definition of DNA Length:
- The length of DNA is typically measured by the number of nucleotides it contains or the number of base pairs, which are pairs of nucleotides.
- The length of DNA is a characteristic feature of an organism.
Examples of DNA Length:
- Examples of DNA lengths for various organisms are provided:
  - Bacteriophage φ ×174: 5386 nucleotides
  - Bacteriophage lambda: 48502 base pairs (bp)
  - Escherichia coli: 4.6 × 10^6 base pairs (bp)
  - Haploid content of human DNA: 3.3 × 10^9 base pairs (bp)
Discussion of DNA Structure:
- The text introduces the structure of DNA as a long polymer but does not delve into specific details in this excerpt.

5.1.1 Structure of Polynucleotide Chain

Composition of Nucleotides:
- Nucleotides consist of three components: a nitrogenous base, a pentose sugar (ribose for RNA and deoxyribose for DNA), and a phosphate group.
- Nitrogenous bases include purines (adenine and guanine) and pyrimidines (cytosine, uracil, and thymine).
Formation of Nucleosides and Nucleotides:
- Nucleosides form when a nitrogenous base is linked to the 1′ C pentose sugar via a N-glycosidic linkage.
- Nucleotides form when a phosphate group is linked to the 5′ C of a nucleoside via a phosphoester linkage.
Structure of Polynucleotide Chains:
- Polynucleotide chains are formed by linking nucleotides through 3′-5′ phosphodiester linkages.
- The backbone of a polynucleotide chain consists of sugar and phosphate groups, while nitrogenous bases project from the backbone.
Additional Features of RNA:
- RNA contains an additional -OH group at the 2′ position in the ribose.
- Uracil replaces thymine in RNA.
Discovery of DNA as Genetic Material:
- Friedrich Miescher identified DNA as an acidic substance in the nucleus in 1869, naming it “nuclein.”
- Technical limitations delayed the elucidation of DNA’s structure until 1953.
Double Helix Model:
- James Watson and Francis Crick proposed the double helix structure of DNA based on X-ray diffraction data.
- Erwin Chargaff’s observation of constant ratios between adenine-thymine and guanine-cytosine pairs supported their model.
- Base pairing between complementary strands allows for prediction of sequence in one strand based on the other.
Salient Features of DNA Double Helix:
- Made of two anti-parallel polynucleotide chains with sugar-phosphate backbones.
- Bases paired through hydrogen bonds: adenine with thymine (or uracil) and guanine with cytosine.
- Coiled in a right-handed fashion with a pitch of 3.4 nm and approximately 10 base pairs per turn.
- Stability conferred by stacking of base pairs and hydrogen bonds.
Central Dogma of Molecular Biology:
- Francis Crick proposed the Central Dogma, stating genetic information flows from DNA to RNA to protein.
- Some viruses reverse this flow, from RNA to DNA.
Reverse Flow Process:
- A simple name for the reverse flow process from RNA to DNA is suggested.

5.1.2 Packaging of DNA Helix

Packaging of DNA in a Mammalian Cell:
- The length of DNA double helix in a typical mammalian cell is calculated to be approximately 2.2 meters, far exceeding the nucleus’s dimensions.
- DNA is packaged in the nucleus using proteins to form a structure known as chromatin.
Calculating Number of Base Pairs in E. coli DNA:
- Given the length of E. coli DNA as 1.36 mm, you can calculate the number of base pairs using the formula: Number of base pairs = Length of DNA / Distance between consecutive base pairs.
- Using the provided values, you can calculate the number of base pairs in E. coli DNA.
Packaging of DNA in Prokaryotes (E. coli):
- In prokaryotes like E. coli, DNA is not scattered throughout the cell but organized in a region called the nucleoid.
- DNA in the nucleoid is organized into large loops held by proteins.
Packaging of DNA in Eukaryotes:
- In eukaryotes, DNA is packaged around histone proteins to form nucleosomes.
- Histones are positively charged proteins rich in lysine and arginine residues.
- A nucleosome consists of DNA wrapped around a histone octamer, typically containing 200 base pairs of DNA.
- Nucleosomes constitute the repeating unit of chromatin, forming a “beads-on-string” structure.
- Chromatin fibers further coil and condense during cell division to form chromosomes.
Organization of Chromatin:
- Chromatin can be loosely packed (euchromatin) or densely packed (heterochromatin).
- Euchromatin is transcriptionally active, while heterochromatin is inactive.
Theoretical Number of Nucleosomes in a Mammalian Cell:
- The number of nucleosomes in a mammalian cell can be theoretically calculated based on the length of DNA and the length of DNA wrapped around each nucleosome.

5.2 THE SEARCH FOR GENETIC MATERIAL

Early Discoveries:
- Friedrich Miescher’s discovery of nuclein and Gregor Mendel’s principles of inheritance were significant milestones in genetics during the late 19th century.
Focus on Chromosomes:
- By 1926, scientific inquiry had progressed to the molecular level in the search for the mechanism of genetic inheritance.
- Previous work by scientists like Walter Sutton, Thomas Hunt Morgan, and others had identified chromosomes, located in the nucleus of most cells, as carriers of genetic information.
Unanswered Question:
- Despite advancements, the identity of the molecule serving as the genetic material remained elusive.
- While chromosomes were implicated, the specific molecule responsible for carrying genetic information had not yet been identified.

Transforming Principle

Experiment with Streptococcus pneumoniae:
- Frederick Griffith conducted experiments with Streptococcus pneumoniae, a bacterium responsible for pneumonia.
- Two distinct strains were observed: smooth shiny colonies (S) with a mucous coat and rough colonies (R) lacking the coat.
Observation of Transformation:
- Mice infected with the S strain (virulent) died from pneumonia, while those infected with the R strain did not.
- Griffith found that heat-killed S strain bacteria did not kill mice when injected alone, but when a mixture of heat-killed S and live R bacteria was injected, the mice died. Moreover, living S bacteria were recovered from the dead mice.
Conclusion of Transformation:
- Griffith concluded that the R strain bacteria had been transformed by a “transforming principle” transferred from the heat-killed S strain.
- This principle enabled the R strain to synthesize a smooth polysaccharide coat and become virulent, suggesting that it was responsible for the transfer of genetic material.
Limitations of the Experiment:
- While Griffith’s experiments demonstrated the concept of transformation and the transfer of genetic material, the biochemical nature of this material was not defined.

Biochemical Characterisation of Transforming Principle

Certainly! DNAs and DNase are different in terms of their composition and function:

Composition:
- DNA (deoxyribonucleic acid) is a nucleic acid composed of nucleotides containing a sugar (deoxyribose), phosphate group, and nitrogenous bases (adenine, thymine, cytosine, and guanine).
- DNase (deoxyribonuclease) is an enzyme that catalyzes the hydrolysis of DNA, breaking it down into smaller fragments. DNase is typically a protein.
Function:
- DNA serves as the genetic material, carrying hereditary information and encoding instructions for the synthesis of proteins and other molecules essential for cell function and development.
- DNase functions to degrade DNA, either as a defense mechanism against foreign DNA (such as in the immune response to bacterial infections) or as part of cellular processes like DNA repair and programmed cell death (apoptosis).
Specificity:
- DNA is specific to its genetic function, determining the traits and characteristics of an organism.
- DNase specifically targets and breaks down DNA molecules, cleaving the phosphodiester bonds between nucleotides.

5.2.1 The Genetic Material is DNA

Bacteriophages and Bacterial Infection:
- Bacteriophages are viruses that infect bacteria.
- The viral genetic material enters the bacterial cell during infection, causing the cell to produce more virus particles.
Experimental Approach:
- Hershey and Chase aimed to determine whether it was protein or DNA from the viruses that entered the bacteria.
- They grew some viruses in a medium containing radioactive phosphorus and others in a medium containing radioactive sulfur.
Radioactive Labeling:
- Viruses grown in the presence of radioactive phosphorus contained radioactive DNA because DNA contains phosphorus.
- Viruses grown in the presence of radioactive sulfur contained radioactive protein because protein contains sulfur.
Infection of Bacteria:
- Radioactive phages were allowed to infect E. coli bacteria.
- As the infection progressed, the viral coats were removed from the bacteria by agitating them in a blender, and the virus particles were separated from the bacteria by centrifugation.
Results:
- Bacteria infected with viruses containing radioactive DNA became radioactive, indicating that DNA was the material passed from the virus to the bacteria.
- Bacteria infected with viruses containing radioactive protein did not become radioactive, indicating that proteins did not enter the bacteria from the viruses.
Conclusion:
- The experiments conclusively demonstrated that DNA, not protein, is the genetic material passed from virus to bacteria.

5.2.2 Properties of Genetic Material (DNA versus RNA)

Sugar Moiety:
- DNA contains deoxyribose sugar, which lacks a hydroxyl group (-OH) at the 2′ position.
- RNA contains ribose sugar, which has a hydroxyl group (-OH) at the 2′ position.
Nitrogenous Bases:
- DNA contains the nitrogenous bases adenine (A), thymine (T), cytosine (C), and guanine (G).
- RNA contains adenine (A), uracil (U), cytosine (C), and guanine (G). Uracil replaces thymine in RNA.

Regarding the criteria for a molecule to act as genetic material:

Replication:
- Both DNA and RNA have the ability to direct their own duplication through base pairing and complementarity.
Chemical and Structural Stability:
- DNA is more chemically and structurally stable than RNA due to the presence of deoxyribose sugar and absence of a 2′-OH group, making it less reactive and more resistant to degradation.
Mutation:
- Both DNA and RNA can undergo mutations, but RNA mutates at a faster rate due to its instability, leading to faster evolution in viruses with RNA genomes.
Expression of Characters:
- RNA can directly code for the synthesis of proteins, while DNA relies on RNA as an intermediary for protein synthesis. RNA is more efficient in expressing genetic information.

5.3 RNA WORLD

RNA as the First Genetic Material:
- RNA is believed to have preceded DNA as the genetic material in early life forms.
- RNA is capable of storing genetic information and catalyzing biochemical reactions, making it a versatile molecule for early life processes.
Role of RNA in Early Life Processes:
- Essential life processes such as metabolism, translation (protein synthesis), and splicing (RNA processing) are thought to have evolved around RNA.
- RNA acted both as a genetic material and as a catalyst, catalyzing important biochemical reactions in living systems.
RNA’s Reactivity and Instability:
- RNA’s ability to act as a catalyst made it reactive and unstable.
- The reactive nature of RNA could have led to errors or mutations, contributing to its instability over time.
Evolution of DNA from RNA:
- DNA is believed to have evolved from RNA through chemical modifications that increased its stability.
- DNA’s double-stranded structure and complementary base pairing provided additional stability and resistance to changes.
Evolution of DNA Repair Mechanisms:
- DNA has evolved repair mechanisms to correct errors and maintain its integrity over generations.
- These repair mechanisms help ensure the stability and fidelity of the genetic material.