DNA discovery

Welcome to MMB Part 2: Molecular Biology

Topics Covered

  • History of DNA discovery

  • Basic genetics

  • Nucleic acid metabolism (replication, transcription, translation)

  • Control of gene expression

  • DNA damage and repair

The Discovery of the Structure and Function of DNA

Dr. Alessandro Siani

  • The historical events leading to the discovery of DNA's structure and function are critical to understanding fundamental biological concepts.

  • Learning the discovery process reveals the questions that drove scientific inquiry and the strategies used by scientists. This knowledge allows a deeper understanding beyond mere factual recall.

Historical Context of Genetics and Evolution

Early Understanding

  • Observable patterns of inheritance and evolution were noted historically.

  • Charles Darwin (1809 – 1882) recognized variability in living beings as a key driver of evolution.

  • Gregor Mendel (1822 – 1884) studied pea plants, quantitatively defining the inheritance of traits through numerical ratios.

Molecular Mechanisms

  • Despite early observations of genetic patterns, the molecular mechanisms governing inheritance and evolution emerged progressively through collaborative research over decades.

Key Discoveries in Nucleic Acids

Discovery of Nuclein

  • 1869: Johann Friedrich Miescher isolated nuclein from pus, named it due to its origin from cell nuclei.

  • 1889: Richard Altmann identified an acidic component in nuclein, coining the term “nucleic acid.”

Composition of Nucleic Acids

  • 1893: Albrecht Kossel discovered that nuclein comprises four bases.

  • 1909: Phoebus Levene identified nucleic acids as having three core components:

    • A sugar

    • An acid

    • An organic base

  • Levene distinguished between DNA and RNA.

Key Experiments Leading to DNA as Genetic Material

Frederick Griffith's Experiment (1928)

  • Griffith discovered a transforming principle through experiments with smooth (virulent) and rough (nonvirulent) bacterial strains:

    • Molecular factor in smooth strain could transform rough strain into virulent form.

    • The molecular identity of this transforming principle was unknown.

Avery, MacLeod, and McCarty (1944)

  • Confirmed that Griffith's transforming principle is DNA. Experimental details include:

    • Use of protease and DNase experiments.

    • Result: Mice injected with the heat-killed smooth strain plus rough strain and DNase survived, confirming that DNA is the transforming agent.

Establishing DNA as Genetic Material

Early 20th Century Views

  • Many biologists viewed proteins as the sole carriers of genetic information due to their complexity.

Hershey & Chase Experiment (1952)

  • Demonstrated that DNA is the genetic material:

    • Element present in proteins but not in DNA: Sulphur

    • Element present in DNA but not in proteins: Phosphorus.

Structure of DNA

Chargaff’s Rules (1950s)

  • DNA base composition varies across species but remains consistent across tissues within the same species:

    • The relationship: A = T and G = C.

    • Resultant equality of purine and pyrimidine residues: A+G=T+C.A + G = T + C.

Rosalind Franklin's Contribution (1952)

  • Utilized X-ray diffraction to reveal the helical structure of DNA.

  • Concluded that nitrogenous bases are internally located while the sugar-phosphate backbone is external.

Watson and Crick Model (1953)

  • Proposed the double helix structure:

    • Two strands composed of alternating sugar and phosphate molecules.

    • Adenine pairs with thymine (2 hydrogen bonds)

    • Guanine pairs with cytosine (3 hydrogen bonds).

Understanding Genetic Expression

Current Knowledge

  • DNA is the genetic material containing nucleotide sequences that direct its replication and protein synthesis that determine organism traits.

Nirenberg and Matthaei's Experiment (1961)

  • Focused on cracking the genetic code using synthetic RNA:

    • Experiment specified which amino acids correspond to specific codons.

    • Example Results:

    • UUU encodes phenylalanine

    • AAA encodes lysine

    • CCC encodes proline.

Mutation and Its Effects

Genetic Information Changes

  • Mutation in a gene can alter the amino acid sequence:

    • Example: Normal adult B-globin gene (HBBAHBB_A)

    • Mutation creates a sickle-cell variant (HBBSHBB_S) resulting in altered red blood cell shape and function affecting oxygen transport.

Milestones in Genetics

φX174 - The First DNA Genome Sequenced (1977)

  • Work by Frederick Sanger utilized a new sequencing method for the bacteriophage φX174, leading to receiving the Nobel Prize in Chemistry in 1980.

The Human Genome Project

Goals

  • A comprehensive project aimed to sequence the entire human genome, appearing as a catalog of DNA.

  • Genomics defined as the analysis of DNA sequences which requires technology, robotics, and computer science.

Key Concepts

  • DNA (or RNA in some viruses) serves as the genetic material.

  • Nucleotide sequences vary among organisms.

  • Structure of DNA is a double helix.

  • DNA sequences hold instructions for replication and synthesis of proteins, determining organismal traits.