Chapter 11

DNA Replication and Historic Experiments

• Importance of Small Particles:

  • Small particles (DNA) carry genetic information.

  • Understanding DNA and its replication are crucial for genetics and molecular biology.

• Griffith's Experiment:

  • Conducted experiments with pneumonia bacteria.

  • Used both pathogenic (deadly) and nonpathogenic (good) bacteria.

  • Key Findings:

    • When mice were injected with a mixture of dead pathogenic bacteria and living nonpathogenic bacteria, the mice died.

    • Discovery of Transformation: The nonpathogenic bacteria incorporated DNA from the dead bacteria and became pathogenic.

Key Contributions to DNA Understanding

• Avery, MacLeod, and McCarty:

  • Investigated the nature of the transforming principle.

  • Focused on whether DNA or proteins were responsible for transformation in bacteria.

  • Key Experiment:

    • By isolating DNA and proteins, they concluded that DNA was the molecule responsible for transformation.

• Hershey and Chase Experiment:

  • Further clarified that DNA is the genetic material.

  • Used radioactive markers to track DNA and proteins separately in bacteriophages.

  • Findings:

    • The DNA entered the bacteria and was found in the pellet after centrifugation, confirming DNA as the genetic material.

Structure of DNA

• DNA Composition:

  • DNA made up of nucleotides consisting of a sugar, phosphate group, and nitrogenous bases (A, T, C, G).

  • The double helix structure with base pairs held together by hydrogen bonds.

• Base Pairing Rules:

  • Adenine (A) pairs with Thymine (T).

  • Guanine (G) pairs with Cytosine (C).

  • In RNA, Thymine is replaced by Uracil (U).

• DNA Replication Models:

  • Conservative Replication: Original strands remain together, while two new strands are created.

  • Semi-conservative Replication: Each new DNA strand consists of one original and one new strand, which is the actual mechanism.

  • Dispersive Replication: Segments of new and old DNA are interspersed in the two strands (less likely).

DNA Repair and Mutations

• DNA Repair Mechanisms:

  • Involves comparing the new strand with the original to detect errors.

  • Tools like CRISPR used for gene editing to correct mutations.

• Types of Mutations:

  • Frameshift Mutations: Insertion or deletion of one or more nucleotides can shift the reading frame.

  • Nonsense Mutation: Changes a normal codon into a stop codon, prematurely terminating protein synthesis.

  • Base Substitution: A single nucleotide is changed, which may or may not affect protein function, e.g., sickle cell anemia.

Population Genetics and Medical Implications

• Variability in Alleles:

  • Genetic variation exists within populations, often higher than between different racial groups.

  • Environmental factors also play a crucial role in genetic expression and disease.

• Case Studies:

  • Sickle cell anemia primarily linked with populations of African descent but also present in others due to different environmental factors.

  • Cystic fibrosis is more common in certain populations, emphasizing the influence of genetic history.

• Bias in Medicine:

  • Recognition of biases due to historical gene expression models.

  • Important changes in medical practices based on improved understanding of genetics.

Gene Expression and Protein Synthesis

• Process Overview:

  • Transcription: Copying DNA to messenger RNA (mRNA) using RNA polymerase.

  • Translation: Converting mRNA into proteins using ribosomes and transfer RNA (tRNA).

• Key Steps in Transcription:

  • RNA polymerase binds to a promoter and synthesizes mRNA by pairing bases, replacing thymine (T) with uracil (U).

• RNA Processing:

  • Editing of mRNA involving removal of introns and addition of a 5’ cap and poly-A tail for stability and transport.

• Translation Process:

  • mRNA codons matched with tRNA carrying corresponding amino acids.

  • Start codon (AUG) signals where translation begins, and stop codons signal termination.

Conclusion

• The understanding of DNA, its replication and repair, mutations, and the genetic basis of disease is pivotal in both education and the medical field.

• Ongoing research continues to unravel the complexities of genetics and its application in healthcare.