History of DNA
How we came to know it as we do today
HISTORY
1869 – Friedrich Miescher – “discovered” DNA in nucleus 1909 – Archibald Garrod – lack of inheritance of certain proteins. Proteins are genetic material 1928 – Fredrich Griffith – Identified DNA as source of genetic material using bacteria 1930’s – Oswald Avery, Colin MacLeod and Maclyn McCarty – Confirmed DNA 1950 – Alfred Hershey and Martha Chase confirmed DNA is biochemical of heredity
Hershey and Chase
HISTORY of STRUCTURE
1909 – Phoebus Levene
Identified ribose and 1929 – identified deoxyribose and determined nucleotide structure
Erwin Chargoff
Early 1950’s
Equal numbers of A & T and C & G
Maurice Wilkins and Rosalind Franklin
X-rayed DNA to show repeating nucleotide structure
Rosalind Franklin
X-ray of double helix
1920 - 1958
HISTORY of STRUCTURE
1953 – James Watson and Francis Crick combined data to create a 3-D model of structure called the double helix
Watson and Crick
Miescher Discovered DNA
1868 Johann Miescher investigated the chemical composition of the nucleus Isolated an organic acid that was high in phosphorus
He called it nuclein
We call it DNA (deoxyribonucleic acid)
Griffith Discovers Transformation
1928 Attempting to develop a vaccine Isolated two strains of Streptococcus pneumoniae
Rough strain was harmless Smooth strain was pathogenic
Griffith Discovers Transformation
1 Mice injected with live cells of harmless strain R. 2 Mice injected with live cells of killer strain S. 3 Mice injected with heat-killed S cells. 4 Mice injected with live R cells plus heatkilled S cells.
Mice live. No live R cells in their blood.
Mice die. Live S cells in their blood.
Mice live. No live S cells in their blood.
Mice die. Live S cells in their blood.
Transformation
What happened in the fourth experiment? The harmless R cells had been transformed by material from the dead S cells Descendents of the transformed cells were also pathogenic
Mystery of the Hereditary Material
Originally believed to be an unknown class of proteins
Thinking was
Heritable traits are diverse Molecules encoding traits must be diverse Proteins are made of 20 amino acids and are structurally diverse
Oswald & Avery
What is the transforming material? Cell extracts treated with protein-digesting enzymes could still transform bacteria Cell extracts treated with DNA-digesting enzymes lost their transforming ability Concluded that DNA, not protein, transforms bacteria
Bacteriophages
Viruses that infect bacteria Consist of protein and DNA Inject their hereditary material into bacteria
© 2006 Brookes/Cole - Thomson
Hershey & Chase’s Experiments
Created labeled bacteriophages
Radioactive sulfur
Radioactive phosphorus
Allowed labeled viruses to infect bacteria Asked: Where are the radioactive labels after infection?
Hershey and Chase Results
35S
remains outside cells virus particle labeled with 35S
DNA (blue) being injected into bacterium
virus particle labeled with 32P
35P
remains inside cells
DNA (blue) being injected into bacterium
Composition of DNA
Chargaff showed:
Amount of adenine relative to guanine differs among species
Amount of adenine always equals amount of thymine and amount of guanine always equals amount of cytosine A=T and G=C
Watson-Crick Model
DNA consists of two nucleotide strands
Strands run in opposite directions Strands are held together by hydrogen bonds
between bases
A binds with T and C with G Molecule is a double helix
Rosalind Franklin’s Work
Was an expert in x-ray crystallography
Used this technique to examine DNA fibers
Concluded that DNA was some sort of helix
The DNA Story
Once the chromosomal theory of inheritance was widely accepted, scientists turned their attention to studying the chromosome.
Histone = protein
Why did researchers think that protien was the genetic material? DNA was too simple and too uniform DNA consists of 4 different nucleotides Protein consists of 20 different amino acids Proteins have a wide variety of functions What organisms were initially studied? Bacteria and viruses, since they were so simple
1928 - Frederick Griffith
Streptococcus pneumoniae, a bacteria that causes pneumonia in mice was studied
© 1999 Addison Wesley Longman, Inc.
Evidence that Viral DNA can Program Cells
Hershey and Chase used bacteriophage , viruses that infect bacteria. The virus consists of a protein coat on the outside and a nucleic acid in the core.
© 1999 Addison Wesley Longman, Inc.
Circumstantial Evidence for DNA:
Prior to mitosis Eukaryotic cell doubles its DNA This DNA distributes exactly evenly to the two daughter cells formed at the end of mitosis An organisms’ diploid cells has twice the DNA as its haploid gametes.
Experimental Evidence For DNA structure:
Chargaff (1947) analyzed DNA composition of different organisms. Franklin and Wilkins X-ray crystallography pictures gave evidence for double helix DNA nucleotide backbone connection was known.