History of DNA

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Pre-Mendelian Theories of Heredity

Pangenesis (Hippocrates, 400 BCE)

  • Proposed that "gemmules" from all body parts travel to reproductive cells.
  • Flaw: No experimental evidence; purely speculative.

Preformationism (17th–18th Century)

  • Suggested sperm or eggs contained a miniature human ("homunculus").
  • Disproven by microscopy showing embryonic development.

Blending Inheritance (Darwin’s Era)

  • Hypothesized that parental traits "blend" irreversibly in offspring.
  • Contradicted by: Mendel’s discrete inheritance patterns.

Gregor Mendel’s Foundation (1865)

Experiments: Crossed pea plants (Pisum sativum) tracking 7 traits (e.g., seed shape, flower color).

Key Laws:

  • Law of Segregation: Alleles separate during gamete formation.
  • Law of Independent Assortment: Traits are inherited independently (later modified for linked genes).

Limitations:

  • Ignored chromosomes (discovered later by Waldeyer in 1888).
  • Work was ignored until 1900 (rediscovered by Correns, de Vries, Tschermak).

Discovery of Nucleic Acids (1869–1909)

1869: Friedrich Miescher

  • Isolated "nuclein" from white blood cell nuclei (later named DNA by Altmann, 1889).
  • Key Insight: Identified phosphorus-rich acidic substance, distinct from proteins.

1880s: Albrecht Kossel

  • Identified DNA’s nitrogenous bases (A, T, C, G).

1910: Phoebus Levene

  • Proposed the "tetranucleotide hypothesis" (incorrectly suggested DNA was a simple repeating sequence).

The Search for Genetic Material (1928–1952)

    Griffith’s Transformation Experiment (1928)

  • Experiment: Used Streptococcus pneumoniae (S-strain vs. R-strain).

Heat-killed S-strain + live R-strain → Dead mice (R-strain transformed).

  • Conclusion: A "transforming principle" transferred virulence.

    Avery-MacLeod-McCarty (1944)

  • Breakthrough: Purified Griffith’s "transforming principle" and treated it with:
    • Proteases (no effect on transformation).
    • DNase (transformation stopped).
  • Conclusion: DNA is the genetic material (not protein or RNA).

    Hershey-Chase Experiment (1952)

  • Method: Used T2 bacteriophage (DNA labeled with ³²P, protein with ³⁵S).
Only ³²P (DNA) entered bacterial cells during infection.

  • Proof: DNA (not protein) carries genetic instructions.

Decoding DNA Structure (1950–1953)

    Chargaff’s Rules (1950)

  • Findings:

A = T, C = G in all species.

Base ratios vary between species (e.g., human DNA: ~30% A, ~20% C).

  • Significance: Hinted at complementary base pairing.

    Rosalind Franklin’s X-ray Diffraction (1952)

  • Helical structure (10Å diameter, 34Å per turn).
  • Two forms: "A" (dry) and "B" (hydrated, biologically relevant).
  • Uncredited: Watson and Crick used her data without permission.

Watson & Crick’s Model (1953)

  • Proposed the double helix model of DNA.
  • Key features:
    •     Two antiparallel strands
    •     Held together by base pairing (A–T, G–C)
    •     Right-handed helix

Advances in DNA Understanding

Meselson-Stahl Experiment (1958)

  • Proved that DNA replication is semi-conservative (each daughter molecule gets one old and one new strand).

Discovery of mRNA, tRNA, and rRNA (1960s)

  • Explained the central dogma: DNA → RNA → Protein.

Genetic Code Cracked (1966)

  • Nirenberg, Khorana, and others deciphered how triplet codons determine amino acids.

Molecular Biology Revolution

Restriction Enzymes Discovered (1970s)

  • Enabled DNA cutting, opening doors to genetic engineering.

Recombinant DNA Technology (1973)

  • Paul Berg, Herbert Boyer, and Stanley Cohen pioneered techniques to combine DNA from different organisms.

Polymerase Chain Reaction (PCR) – 1983

  • Invented by Kary Mullis.
  • Allowed amplification of specific DNA sequences—crucial for diagnostics, forensics, cloning.

Genomics Era

Human Genome Project (1990–2003)

  • International collaboration to sequence all ~3 billion base pairs of human DNA.
  • Revealed the complete blueprint of human genes.

CRISPR-Cas9 Gene Editing (2012)

  • Discovered by Jennifer Doudna and Emmanuelle Charpentier.
  • Allows precise editing of DNA sequences in living organisms.
  • Nobel Prize in Chemistry (2020).


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