Big Questions What does DNA look like? How does DNA work? How was the structure and function of DNA determined?

The 20th Century By the middle of the 20th century, genetics was well established as a field of study. It was known that traits were inherited, but it was not known how that process happened. Mathematical analysis can only go so far. What were genes made of? How did they work? Nobody knew. The discovery of DNA's role in inheritance is arguably the most significant contribution to understanding how life works. It was not the result of any one person, but the final result of decades of investigation by many different researchers. Friedrich Miescher Discovered nucleic acids (1869)

Chromosomes Observation of chromosomes during cell division demonstrates that they act in a way consistent with molecules of heredity. Chromosomes are made of 2 ingredients: DNA and protein. This suggests that heritability is controlled by one of these two molecules. Before 1940 (or so), most biologists thought that protein was probably the molecule responsible for inheritance (why?). No one had any idea about DNA's structure or function.

Frederick Griffith: Transformation 1928 A Scottish Microbiologist Discovered that bacteria could give other bacteria heritable traits, even after they were dead.

Avery, McCarty & MacLeod: Griffiths Refined (1944) Refined Griffith's Experiment Exposed R-strain Streptococcus to purified S-strain protein, and purified S-strain DNA Only the bacteria exposed to the S-strain DNA were transformed Not enough evidence for the haters

Hershey & Chase: The "Blender" Experiment (1952) Worked with bacteriophages Conclusively demonstrated that DNA was the molecule of heredity Tagged phage DNA and protein with radioactive atoms and tracked the transmission of that radioactivity to infected bacteria Nobel Prize: Hershey (1969)

Erwin Chargaff's "Rules“ (1950-1952) Demonstrated two major rules of DNA composition All species have different amounts of adenine, thymine, cytosine and guanine in their DNA. In every species: the amount of adenine = the amount of thymine and the amount of cytosine = the amount of guanine

WHY DOES THIS MATTER? https://www.youtube.com/watch?v=HvJlnujmYcg

Watson & Crick, Franklin & Wilkins (1953)

Two competing teams to determine the structure of DNA Watson and Crick used X-ray diffraction data developed by Rosalind Franklin to develop their "double helix" model of DNA Nobel Prize: Watson, Crick & Wilkins (1962)

Nucleotide Deoxyribose sugar Phosphate group Nitrogenous base A, T, C, G

Nitrogenous Bases 4 Bases Purine – Double ring Adenine (A), Thymine (T), Cytosine (C), Guanine (G) Purine – Double ring A and G Pyrimidine – single ring T and C

Bases on one strand are covalently bonded to each other ("phosphodiester bonds") Bases on opposite strands are hydrogen bonded to each other ("base pairs"). Adenine = Thymine (2 H bonds) Cytosine = Guanine (3 H bonds)

The First Puzzle Solved!

Chromosomes are densely packed double-stranded DNA molecules (with hundreds of millions of base pairs)

Chromosome Structure DNA wraps around histones Chromatin Fibers DNA wraps around histones histones form nucleosome Histones Nucleosomes

Plasmids small, circular, double-stranded DNA molecule Different from chromosomal DNA naturally exist in bacterial cells some eukaryotes Often provide bacteria with genetic advantages antibiotic resistance Hundreds to thousands of base pairs each daughter cell receives a copy of each plasmid Bacteria can also transfer plasmids to one another through conjugation

Make sure you can… Explain how the structure of DNA is related to its function as the information storage molecule in living systems. Explain the contributions of all scientists discussed in this presentation to understanding DNA structure. Describe how the historical development of scientific understanding of the structure of DNA is an example of science as a collaborative, evidentiary, and technological process.