P02 The Hereditary Material Flashcards
The history that lead to the discovery of the structure of the DNA molecule consisted of what 2 streams?
- Genetics: Genetics became so powerful that geneticists thought they could solve any problem by the means of genetics, could understand biochemical pathways by the means of genetics
- Physics: Especially X-ray crystallography. Study of large molecules by bounding x-rays off them
Double helix structure suggested its function
- The copying of genetic information (strand unwinding)
2. DNA could divide (two identical strand)
Who discovered DNA
Friedrich Miescher (watson and crick just discovered shape)
How did Friedrich Miescher discover DNA
isolated nuclei from pus and found a new kind of molecule; he called it ‘nuclein’
-nuclein had acidic and basic part (nucleic acid = acidic part, histones = basic part)
What did Friedrich Miescher think the function of nuclein was
- thought it was involved in heredity
- knew the significance of nuclei in heredity
What did Albrecht Kossel do?
- discovered the 5 kinds of bases in nucleic acids (G,C,A,T/U)
- distinguished between DNA and RNA (Miescher didn’t do this)
Phoebus Aaeron Levene
- explained the structure of nucleotides and differences in structure between DNA and RNA (deoxyribose and ribose)
- tetra nucleotide hypothesis (made up of equal amounts of ACGT)
What did Levene suggest about the 4 base pairs of DNA
- present in equal amounts (WRONG)
- bad
Levene’s history
- Jewish
- Immigrated to US and worked as physician then burned out and became a biochemist
Alcaptonuria was studied by who?
- Archibald Garrod
- soon after rediscovery of Mendel’s laws
What did he study to observe Alcoptonuria
- family pedigrees
- showed that it is inherited as a mendelian recessive trait
Alcoptonuria symptoms
- not able to get rid of homogentisic acid
- excreted in the urine, turns black upon exposure to air
What did Archibald guess about alleles
- guessed that 2 recessive alleles produces 2 defective enzymes
- concluded that a normal allele produced an enzyme for the metabolism of homogentisic acid
What did Franz Moewus study
- genetics of sexuality of chlamydomonas eugametos (unicellular green algae) in 1930
- associated mendellian mutation with an inability to produce sex hormones
Similarities between Franz Moewus and Archibald Garrod
-associated genes with biochemical functions
What happened with Franz Moewus work
He was caught making up data so his work was discounted
Who lead to the fusion of genetics and biochemistry?
- Beadle and Tatum
- Studied pathways that involved 3 genes. Knocking out one gene lead to a different pathway.
- gene knockouts effected different parts of the same pathway.
- specific mutants lacks specific enzyme
What was the first protein to be studied in structural and functional detail?
Haemoglobin
Who discovered sickle cell anemia
Linus Pauling and co workers
-sickle cell is inherited in simple mendelian fashion, also related to malformed protein
What is sickle cell anemai
-malformed version of protein haemoglobin
What book did Erwin Schrodinger write?
“What is Life” 1944
What did Erwin Schroding study
- physicist
- founder of wave mechanics
What did “What is Life” explain
- study of living matter might reveal unknown laws of physics
- genes must be made up of a few hundred-few thousand atoms to account for genetic stability (any more would allow for too frequent gene destruction)
- genes must be aperiodic crystals - every atom or group of atoms has a particular place and role in the gene
What did Schroding give lectures about
-unknown laws of physics
Aperiodic crystals
-arrangement of atoms in which every atom has a role in containing/transmitting information in gene
sugar-coated microbe
- Streptococcus pneumoniae
- model that showed that genes are made up of DNA
2 strains of Streptococcus pneumoniae
- S (smooth) strain - causes pneumonia in mice; surrounded by a polysaccharide coat that renders it invisible to the mouse immune system
- R (rough) strain - harmless to mice; not surrounded by coat so the immune system deals with it
What did Fred Griffith discover?
transformation of the R strain to the S strain
What happens when heat-killed S cells are injected into mouse
mouse lives
What happens when R cells are transferred into mouse
mouse lives
What happens when heat killed S cells mixed with R cells are injected into mouse
mouse dies
-living S cells are found in blood sample from the dead mouse
What do these mouse experiments suggest?
Perhaps a (genetic material) gene is transferred from the dead S cells to the living R cells enabling the R cells to make a protective polysaccharide coat (thus the R cells become S cells and kill mouse)
What did Fred Griffith think this genetic material passed from S cell to R cell was
- DNA
- a lot of people didn’t think that DNA was this material, a lot of people thought it was proteins
Alfred Hershey and Martha Chase and T2 were involved in what
Phage genetics
What are phages?
- viruses of bacteria that inject their genes into a host bacterial cell
- expresses their genes and makes more phage particles
- when phages inject their genes the inject DNA not protein
What was the Hershey Chase experiment
-mixed radioactively labelled phage with bacteria
-agitated in blender, separated phages outside the bacteria from the cells and their content
-centrifuged so bacteria form a pellet at the bottom of test tube
-measure the radioactivity in the pellet and the liquid
(Radioactivity is in the pellet so the T2 protein is outside the liquid. Therefore the DNA is what is in the cell)
James Watson
- did PhD on phage genetics
- but went to uni of Cambridge to work on X-ray crystallography of proteins
Why did James Watson switch from Biology to physics?
to learn X-ray crystallography so he could explain the structure of DNA
Francis Crick
- was a physicist still working on his PhD in his mid-thirties
- also at Cambridge working on X-ray crystallography of hemoglobin in same lab as Watson
Who worked on mutations in WWII
Crick
What did Linus Pauling discover?
found alpha helix (one of first macromolecules)
-structural theme in biology that Watson an Crick found interesting
Linus Pauling and model building
-played with models, lead to a lot of his insights
What were Chargaff’s rules
A=T, G=C
-Lavine thought that everything was equimolar, Chargaff showed that it was only At and Gc
Rosalind Franklin and Maurice Wilkins
X-ray diffraction pictures of crystallized DNA
-Rosalind Franklin died before nobel prize was awarded
What did Watson and Crick think?
thought that DNA –> RNA –> protein
-thought DNA was the most golden of molecules -people who thought proteins carried hereditary info were idiots
Watson and crick used what from others
x-ray pictures of others
rosalind franklin
What did Watson and Crick propose in 1951
- triple helical model of DNA
- 3 polynucleotide strands and the bases pointing out
Linus Paulings DNA triple helix
- pauling prepared paper for publication (wrong)
- the race was on
Wilkins showed watson what?
-Rosalind Franks picture of B-DNA took late in 1952
What 2 models did Watson consider after seeing the picture
1) A-A, C-C, G-G, T-T
2) A-T and G-C pairs (noticed that this explains Charagraff’s rules)
What does crick point out
- the two strands must run in opposite (antiparallel) directions
- polarity?
