Molecular Biology: Chromosomes and DNA Structure

Abnormal Chromosome Number

  • Nondisjunction:

    • Definition: Nondisjunction is the failure of homologous chromosomes to separate normally during meiosis.

    • Result: This process leads to one gamete receiving two copies of the same chromosome type, while another gamete ends up with no copy of that chromosome.

    • Consequences: Can lead to aneuploidy in offspring, which is having an abnormal number of a particular chromosome.

  • Types of Nondisjunction:

    • Meiosis I Nondisjunction: Homologous chromosomes fail to separate.

    • Meiosis II Nondisjunction: Sister chromatids fail to separate.

  • Aneuploidy:

    • Definition: A chromosomal condition resulting from fertilization of two gametes that have undergone nondisjunction.

    • Example Types:

    • Monosomic zygote: Contains only one copy of a particular chromosome (2n - 1).

    • Trisomic zygote: Contains three copies of a particular chromosome (2n + 1).

The Molecular Basis of Inheritance

  • Overview of DNA:

    • In 1953, James Watson and Francis Crick proposed the double-helical model for DNA (deoxyribonucleic acid).

    • Significance:

    • Hereditary information is encoded in DNA and is reproduced in all cells of the body.

    • DNA influences biochemical, anatomical, physiological, and to some extent, behavioral traits.

  • The Search for Genetic Material:

    • Early 20th Century: Morgan's research indicated that genes are located on chromosomes, making DNA and protein candidates for genetic materials.

    • Griffith’s Experiment (1928): Showed transformation in bacteria, where non-pathogenic strain could become pathogenic when mixed with heat-killed pathogenic cells.

    • Transformation: Defined as a change in genotype and phenotype due to the assimilation of foreign DNA.

  • Avery, McCarty, and MacLeod (1944):

    • Their research concluded that DNA is the transforming substance because only DNA transformed harmless bacteria into pathogenic ones.

    • Skepticism existed due to limited knowledge about DNA at the time.

  • Bacteriophage Studies:

    • Further evidence for DNA as genetic material came from studies of bacteriophages; these are viruses that infect bacteria. Bacteriophages are extensively used in molecular genetics.

  • Hershey-Chase Experiment (1952):

    • Developed a method to show that only one of the two components of T2 bacteriophage (DNA or protein) enters a E. coli cell during infection, confirming DNA as the source of genetic material.

    • Experimental Details:

    • Two batches were used, one with radioactive sulfur in protein and the other with radioactive phosphorus in DNA.

    • Results showed that only the phage DNA entered the bacterial cell, corroborating that DNA carries genetic information.

Structure of DNA

  • Nucleotides:

    • DNA is a polymer made of nucleotides.

    • Each nucleotide consists of three components:

    • A nitrogenous base (Adenine, Thymine, Cytosine, Guanine).

    • A sugar (deoxyribose).

    • A phosphate group.

  • Double Helix Structure:

    • DNA double helix results from base pairing rules where adenine pairs with thymine (A-T) and guanine pairs with cytosine (G-C).

    • Chargaff's rules: Amount of A = T, Amount of G = C, which indicates specific pairing relationships.

  • X-ray Crystallography:

    • Rosaline Franklin and Maurice Wilkins used this method allowing Watson to deduce that DNA was helical, refining the understanding of DNA's structure, dimensions, and base spacing.

    • Key features of DNA:

    • The helical structure shows specific widths indicating a two-stranded molecule (double helix).

DNA Replication

  • Semiconservative Model:

    • Proposed by Watson and Crick, it suggests that during DNA replication, each daughter molecule consists of one old strand and one newly synthesized strand.

  • Mechanics of Replication:

    • More than a dozen enzymes and proteins are involved in the process of DNA replication, ensuring speed and accuracy.

    • Origins of Replication: Sites in the DNA where replication commences and forms replication bubbles.

  • Elongation Mechanism:

    • Leading Strand: Synthesized continuously towards the replication fork.

    • Lagging Strand: Synthesized discontinuously as Okazaki fragments, which are later joined by DNA ligase.

  • Role of Key Enzymes:

    • DNA Polymerase: Responsible for adding nucleotides to the growing strand and requires a primer to initiate synthesis.

    • Primase: Synthesizes a short RNA primer for starting DNA synthesis.

    • Helicase: Unwinds the double helix at replication forks.

    • Topoisomerase: Relieves torsional strain created ahead of the replication fork.

Proofreading and Repairing DNA

  • DNA Polymerase Proofreading: Corrects errors during replication by replacing incorrect nucleotides.

  • Mismatch Repair: Enzymes correct errors in base pairing after DNA has been replicated.

  • Environmental Damage to DNA: DNA can be damaged by various agents, including chemicals, radiation, and UV light.

Telomeres and Aging

  • Telomeres: Protective nucleotide sequences at the ends of eukaryotic chromosomes that prevent the erosion of genes during replication.

    • The shortening of telomeres can be associated with aging, as they may protect against cancer by limiting cell division.