3.1 An Incomplete History of Molecular Biology

3.1 An Incomplete History of Molecular Biology

  • Basics of Molecular Biology

A Genetics Who-Done It

  • Gregor Mendel introduced the concept of genetics in 1859.

  • Scientists were unsure about the hereditary material until the 1920s.

  • The key question: What is the hereditary material that makes us who we are?

The Basis of Heredity

Frederick Griffith (1928)

  • Conducted studies on pathogenic pneumonococcus bacteria in mice.

  • Investigated whether heredity is fixed and unchangeable using two bacterial strains: R-strain (rough, nonvirulent) and S-strain (smooth, virulent).

  • Experiment protocol involved combining heat-killed S-strain with live R-strain.

Griffith Experiment & Transforming Principle

  • Mixed living S-strain, living R-strain, and heat-killed S-strain with live R-strain.

  • Observed the outcomes in mice:

    • Mouse dies with living S strain

    • Mouse lives with living R strain

    • Mouse lives with dead S strain

    • Mouse dies with living R strain + dead S strain (virulent outcome)

Conclusion from Griffith

  • R-strain was transformed into lethal S-strain by a transforming principle from dead S-strain.

  • These findings suggested that heredity could be passed between cells.

Modern Understanding

  • The transforming principle was identified as DNA from the S-strain bacteria.

  • DNA survived the heating of S-strain and was taken up by the R-strain, allowing it to synthesize a protective capsule.

Location of Hereditary Material

Alfred Hammerling (1930s)

  • Studied unicellular green algae species: Acetabularia.

  • Different species produced different cap shapes (disc-shaped and flower-shaped).

  • Conducted grafting experiments on algae stalks and bases.

Hammerling’s Conclusion

  • The base of the algae dictated the cap shape developed, pointing to the nucleus as the home of hereditary material.

  • Modern understanding confirms that the nucleus contains DNA guiding shape formation.

Scientists Study DNA Structure

  • Research on DNA's structure was prioritized due to its importance in heredity.

Rosalind Franklin

  • Contributed significantly to DNA structure discovery through X-ray crystallography.

  • Developed Photo-51, portraying DNA's molecular structure.

  • Maurice Wilkins shared her discoveries without permission, leading to Watson and Crick receiving credit.

Analysis of Photo 51

  • Findings from Franklin's X-ray analysis revealed:

    • DNA forms a helix

    • Twists every 34 angstroms

    • 10 bases per twist and phosphate on the outside

Proof of Hereditary Material

O. Avery, M. McLeod & C. McCarty (1944)

  • Built on Griffith’s work to identify transforming principles as either DNA or protein in pathogenic bacteria.

  • Treated mixtures with enzymes and observed differential outcomes in mouse survival (protease vs DNAase).

Conclusion from Avery et al.

  • DNA is the transforming principle responsible for the virulence of the bacteria, confirmed by results showing different outcomes based on the compound hydrolyzed.

Understanding DNA's Chemical Structure

Erwin Chargaff (1950)

  • Conducted chemical analysis of DNA from various species.

  • Discovered consistent ratios in nucleotide bases, leading to Chargaff's rules.

Chargaff's Findings

  • Established relationships between nucleotide proportions:

    • %A = %T

    • %G = %C

    • Variability in specific ratios depending on organism type.

Practice Questions Based on Chargaff’s Law

  • Provided problems relating to the calculation of nucleotide percentages in DNA samples.

DNA as Hereditary Material Confirmed

Hershey & Chase (1952)

  • Experimented with bacteriophages labeled with radioactive isotopes (35S for proteins and 32P for DNA).

  • Investigated which labeled material entered bacteria upon infection.

Hershey & Chase Conclusions

  • Centrifugation separated phage from bacterial contents.

  • Radioactivity observed inside bacterial cells came from DNA, confirming it as the genetic material.

Understanding Chemical Structure of DNA

Watson & Crick (1953)

  • Developed DNA models from existing data (Chargaff’s laws, X-ray data).

Watson & Crick Conclusions

  • Proposed the double helix structure for DNA with:

    • Anti-parallel strands

    • Hydrogen bonds between base pairs

    • Phosphate-sugar backbone

    • Noted that one twist has 10 base pairs.

Chromosome Structure

  • DNA forms supercoiled chromosomes.

  • DNA wraps around histones to form nucleosomes, aiding in DNA packaging.

Telomeres and Immortality

Elizabeth Blackburn & Carol Greider (1975-1977)

  • Researched telomeres in Tetrahymena, demonstrating them as crucial to chromosome integrity and cellular immortality.

Understanding Telomeres

  • Telomeres are protective caps at chromosome ends consisting of repeating non-coding sequences.

Significance of Telomeres

  • Observed degradation of telomeres upon cell division leads to finite cell lifespan.

Further Experiments with Telomeres

  • Proved that adding telomeres to yeast can protect their chromosomes, demonstrating the protective function of telomeres.