The Hereditary Material

Question 1

What 2 streams of historical study of the hereditary material lead to the discovery of DNA structure?

Answer 1

1. study of genetic function
2. physical study of macromolecules

Question 2

What brought these 2 streams together and why?

Answer 2

the discovery of the DNA double helix brought the study of structure and the study of function together because the structure happened to be very suggestive of function (this is not always the case)

Question 3

Who discovered DNA? How? What was it first called?

Answer 3

Friedrich Miescher (1844-1895)

isolated it from pus from bandages (white blood cells are nucleated)

called it ‘nuclein’ - other macromolecules had been described, but not nucleic acids

Question 4

What did Miescher think about ‘nuclein’s’ (DNA) function?

Answer 4

he thought it could be hereditary because it contained nuclei, which had been established as hereditary

he thought isomers of nuclein might be hereditary variants

Question 5

Who discovered the nitrogenous bases in nucleic acids? how?

Answer 5

Albrecht Kossel (1853-1927)

he looked at both DNA and RNA and determined the 5 types: A, G, T, C, and U

Question 6

Who developed the structure of the nucleotide (base, sugar, phosphorous group) and distinguished between DNA and RNA?

Answer 6

Phoebus Aaron Levene (1869-1940)

Question 7

What was Levene known for?

Answer 7

unfortunately, for getting the model of DNA structure wrong

he proposed the tetranucleotide model of DNA - which impeded the discovery of the true structure for some time

Question 8

What was Levene’s tetranucleotide model of DNA?

Answer 8

he thought the 4 base pairs in DNA were present in equimolar parts (untrue)

Question 9

Which 5 guys were involved in combining biochemistry and genetics?

Answer 9

1. Archibald Garrod - human pedigree studies highlighted Mendelian recessive traits
2. Francis Moewus - sexuality and biochem pathways in a unicellular green alga
3. Beadle and Tatum - a fungi and a mutant - biochem pathway
4. Linus Pauling - hemoglobin and sickle cell anemia

Question 10

Why was hemoglobin significant to biochemical genetics?

Answer 10

it was the first protein to be studied in structural and fucntional detail and had a lot of interesting qualities to study it

it was used to understand sickle cell anemia by Linus Pauling

Question 11

Who was Linus Pauling? Why was he important?

Answer 11

Known as the World’s Greatest Chemist, he introduced quantum mechanics to chemistry

He studied hemoglobin and demonstrated that sickle cell anemia is inherited via a Mendelian recessive gene

He won both a Noble Prize in Chemistry and a Noble Peace Prize for his advocacy against nuclear weapon testing in the US

Question 12

Why was Edwin Schrodinger’s book “What is Life?” so influential in the 1900-30s?

Answer 12

people kind of thought physics was a complete science, so many physicists and chemists left their field to study biology - this book pushed a lot of people in that direction

Question 13

What were the main points in ‘What is Life?”

Answer 13

Schrodinger argued that

the study of living matter might uncover some unknown laws of physics (untrue)

genes must be made up of a small number of atoms to account for genetic stability because of thermal disruption of chemical bonds (also untrue)

genes must be aperiodic crystals = every atom or group has a particular place and a particular role - a tight relationship between structure and function

Question 14

For a long time, it was thought that protein was carrying the genetic information, not DNA.

Which scientists first showed that it was DNA? How?

Answer 14

Avery, McCarty and MacLoad (1932-44) showed that when a gene travelled within bacteria from one cell to another, DNA is what moves it

they did this by killing the proteins = still moved, by killing the lipids = still moved, etc. until DNA didn’t move

Question 15

Avery, McCarty and MacLeod’s work didn’t convince everyone, so who solidified DNA as the hereditary material?

Answer 15

Hershey and Chase with the bacteriophage (virus) T2 - they found that when a virus injects its genes into a bacterial cell, it is injecting DNA

this was enough to convince everyone

Question 16

Who was James Watson (1928-STILL ALIVE?)?

Answer 16

an ornithologist turned phage geneticist turned X-ray crystallographer at U of Cambridge to study proteins (myoglobin)

Worked with Crick to develop DNA double helix

Question 17

Who was Francis Crick (1916-2004)?

Answer 17

a physicist turned x-ray crystallographer at Cambridge to study proteins (hemoglobin) (turned neurobiologist at the end of his career)

Worked with Watson to develop DNA double helix

Question 18

Which modern events in genetics led to W+C’s development of the DNA double helix?

Answer 18

1. Linus Pauling’s a-helix model (and model building influence) = for the stable arrangement of amino acids, it had to be helical
2. Chargaff’s rule about base pairs (A=T, C=G) - not in equimolar amounts like Levene thought
3. polynucleotide strands and polarity
4. X-ray diffraction pictures from crystallized DNA by Rosalind Franklin, Raymond Gosling, and Maurice Wilkins
5. gene replication via complimentary strands

Question 19

What did Watson and Crick provide?

Answer 19

enthusiasm about DNA being the ‘golden molecule’ and a good working relationship

the central dogma (later recognized by Crick as being a term coined in ignorance of its authoritative and unscientific connotations)

a MODEL-based approach that used (Franklin’s) crystallography as evidence

Question 20

What model did W + C first propose to Franklin’s lab? What did she think?

Answer 20

a triple helix with bases pointing out

Franklin said no way
- she thouight at this time that it wasn’t helical and it definitely wasn’t triple

Question 21

What was Linus Pauling’s proposed model that encouraged W+C to get on it and publish their updated version?

Answer 21

he also proposed a triple helix but they knew from Franklin that it wasn’t correct and that someone else would spot his errors and figure it out quickly so they treated it like a race

Question 22

What was the political environment like regarding the structure of the DNA?

Answer 22

kinda heated - they knew there was a Noble Prize at stake

W+C’s supervisor told them to get back on track with their protein studies and to leave the DNA stuff to Franklin’s lab because they were the ones coming out with the data but they didn’t let it go

Question 23

What differed between W+C’s original triple helix model (and Pauling’s model) to their double helix model and Franklin’s work?

Answer 23

Franklin and previously W+C and Pauling were studying A-DNA, but W+C turned to B-DNA, which turned out to be the more biologically relevant form - which Franklin didn’t think would be true

W+C got firsthand advice from an organic chemist in their lab that the components in DNA exist in their KETO tautomeric form, not the enol like all previous literature states

Question 24

What were 6 sources of critical data that led to W+C’s double helix model?

Answer 24

1. nucleotides and polynucleotide strands
2. Chargaff’s rules of base pairs
3. King’s College (Wilkins and Franklin’s) discovery of 2 types of DNA - A and B, which they believed B to be more important
4. physical data from Franklin’s lab which they apparently just used to check their model against afterwards
5. photo 51 from Franklin’s crystallography lab = helical
6. the correct base tautomeric form (Jerry Donahue) = keto, not enol

Question 25

What were the 3 major components of the double helix model by W+C?

Answer 25

1. complimentary base pairing
2. anti-parallel polynucleotide strands
3. stabilization of the molecule by base stacking

Question 26

What are 6 reasons why Franklin didn’t solve the structure first?

Answer 26

1. she wasted time studying A-DNA which ended up not being as biologically relevant and was more difficult to interpret in images
2. she didn’t accept the helical structure at first
3. she didn’t realize the anti-parallel nature of the strands
4. she didn’t consider base pairing
5. she used the enol (wrong) tautomeric forms of the bases
6. she didn’t appreciate the value of model-building and didn’t build any herself

Question 27

Was Franklin cheated?

Answer 27

it’s controversial but not really

W+C did use her MRC data to ‘check their work’ without her permission, but later she said she didn’t see any misconduct

she gave them permission for the photo 51

W, C, Franklin, Wilkins and Gosling all sat down before W+C submitted their model and agreed on a plan:
1. W+C publish their paper about their model
2. Wilkins writes a paper about his lab’s info
3. Franklin and Gosling write a third paper on their lab’s work
All published to the same journal back to back

Question 28

Who received a Noble Prize for the structure?

Answer 28

Watson, Crick and Wilkins

Question 29

In Ch 23, Watson exposes himself as kind of a dick by insulting Rosalind Franklin in what way?

Answer 29

He told her she was incompetent at interpreting x-ray crystallography images of DNA - which was basically her entire job and research - because her inability to see the structures as helical

Question 30

What was Ch 23 by Watson about?

Answer 30

His description of how the discovery of the B DNA and everything led to the double helix structure

he also makes a lot of claims that Franklin was hot tempered and aggressive

Question 31

What did Watson sketch the first drawing of the BDNA structure on?

Answer 31

a newspaper on the train back to Cambridge from dinner with Maurice Wilkins in London

Question 32

What did Watson determine the double helix model depended on?

Answer 32

the water content of the DNA samples -B DNA contained more water than A DNA

Question 33

What did Watson conclude from the image of the B DNA about important biological objects?

Answer 33

they come in pairs