History of Genetics Flashcards
1865: Mendel
Gregor Mendel
–> Two laws of inheritance are identified through Mendel’s pea plant experiments
–> Identified “heritable factor” transmitted between generations
1910: Morgan
Thomas Hunt (T.H.) Morgan
–> Published study showing chromosomes were the carriers of Mendel’s “heritable factors” (genes)
–> It was uncertain whether these heritable factors on the chromosomes were DNA or protein
The case for protein as the heritable factor:
1) Proteins were more studied:
Seemed to have more diversity in the amino acids that was thought to allow for more combination = more complexity = more likely to be our genetic makeup
2) Nucleic acids seemed too uniform to account for the multitude of specific inherited traits
1928: Griffith
Frederick Griffith’s Streptococcus Pneumoniae Experiment
–> Founder of the “transformation principle”
Streptococcus Pneumoniae Experiment:
What is the difference between the strains?
Streptococcus Pneumoniae: Has 2 strains
1) R-Strain (Rough) = NON-pathogenic
–> Appearance: Smaller, no capsule
2) S-Strain (Smooth) = PATHOGENIC
–> Appearance: Bigger, HAS capsule
S-Strain Capsule Function
A polysaccharide coating that masks the bacteria from the immune system (hides it)
Genetic difference between R and S strains:
S-Strain = HAS the variant of the gene that encodes for capsule production
R-Strain = DOES NOT HAVE the variant of the gene that encodes for capsule production
Streptococcus Pneumoniae Experiment:
METHODS
1) Injected mice with different types of streptococcus pneumoniae strains
2) Analyzed whether mice died or not
3) Blood sampling to look at the bacteria strains
Streptococcus Pneumoniae Experiment:
What were the experiment groups?
1) Pathogenic CTRL = Treated cells with LIVING S-Strain
2) NON-Pathogenic CTRL = Treated with LIVING R-Strain
3) Non-Pathogenic “Ctrl.” = Treated with HEAT KILLED S-STRAIN (Dead S-Strain)
4) Test (Combo) Grp. = Treated with MIX:
–> LIVING R-STRAIN
–> HEAT-KILLED S-STRAIN
Streptococcus Pneumoniae Experiment:
What was the result of the mice treated with LIVING S-STRAIN?
Mice DIED –> Pathogenic strain killed the mice
Streptococcus Pneumoniae Experiment:
What was the result of the mice treated with LIVING R-STRAIN?
Mice LIVE –> Non-Pathogenic strain did NOT kill mice
Streptococcus Pneumoniae Experiment:
What was the result of the mice treated with HEAT-KILLED S-STRAIN?
Mice LIVE –> Pathogenic strain was DEAD and so it had no pathogenic effect on the mice (didn’t kill the mice)
Streptococcus Pneumoniae Experiment:
What was the result of the mice treated with the COMBO?
–> MIX = Living R-Strain, Heat-Killed S-Strain
Mice DIE
–> Why? Took blood sample to look at the bacteria
Streptococcus Pneumoniae Experiment:
Combo treated mice blood sample results
LIVING S-STRAIN FOUND
(Strange because the mice had been treated with only DEAD S-strain and living R-strain)
Streptococcus Pneumoniae Experiment:
OVERALL RESULT
The R-Strain cells acquired the pathogenicity trait, turning them into S-Strain cells
–> Some chemical component of the pathogenic cells caused this heritable change
Streptococcus Pneumoniae Experiment:
Conclusion and Discovery
Conclusion: R-Strain bacteria had been “transformed” into S-Strain by some heritable factor
Discovery:
Transformation Principle
Streptococcus Pneumoniae Experiment:
What question remained at the end of the experiment?
–> What was the heritable factor that served as the transforming component?
Transformation (Definition as we know it today)
A change in genotype and phenotype due to the assimilation of external DNA by a cell
1944: Avery, MacLeod, McCarty
Oswald Avery, Colin MacLeod, Maclyn McCarty
–> Identified the “transforming substance” from Griffith’s experiment
–> First evidence of DNA as heritable factor (though most were skeptical of this study and did not accept the results as being accurate = DNA debate continued on until 1952)
Avery, MacLeod, McCarty Experiment:
METHODS
1) Treated different groups of Heat-Killed S-Strain bacteria with different substances that would break down molecules such as proteins, DNA, RNA, lipids, and sugars
2) Mixed these altered heat-killed S-Strain bacteria with LIVING R-Strain
3) Injected these mixtures into mice
4) Analyzed mice survival
Avery, MacLeod, McCarty Experiment:
What were the experiment groups?
1) CONTROL –> NON-TREATED Heat-Killed S-Strain (+ Living R-strain)
TEST GRPS:
2) Heat-Killed S-Strain with LIPIDS AND SUGARS DESTROYED (+ Living R-Strain)
3) Heat Killed S-Strain TREATED with PROTEASES (destroyed proteins) (+ living R-strain)
4) Heat Killed S-Strain TREATED with DNAses (destroyed DNA) (+ living R-strain)
5) Heat Killed S-Strain TREATED with RNAses (destroyed DNA) (+living R-Strain)
Avery, MacLeod, McCarty Experiment:
What was the result of the Control (non-treated) group?
Mice DIE
–> Transformation of R-Strain occurs and they gain the pathogenic ability
Avery, MacLeod, McCarty Experiment:
What was the result of the group with lipids and sugars destroyed?
Mice DIE
–> Transformation of R-Strain still occurs, and they gain the pathogenic ability
–> Destruction of sugars and lipids didn’t stop the transformation, THEREFORE, they are not the heritable factors
Avery, MacLeod, McCarty Experiment:
What was the result of the group treated with proteases?
Mice DIE
–>Transformation of R-Strain still occurs, and they gain the pathogenic ability
–> Destruction of proteins didn’t stop the transformation, THEREFORE, they are NOT the heritable factors
Avery, MacLeod, McCarty Experiment:
What was the result of the group treated with RNAses?
Mice DIE
–> Transformation of R-Strain still occurs and they gain the pathogenic ability
–> Destruction of RNA didn’t stop the transformation, THEREFORE, they are NOT the heritable factors
Avery, MacLeod, McCarty Experiment:
What was the result of the group treated with DNAses?
Mice LIVE
–>Transformation of R-strain DIDNT HAPPEN
–> Destruction of DNA stopped the transformation, THEREFORE DNA IS THE HERITABLE FACTOR OF TRANSFORMATION
Avery, MacLeod, McCarty Experiment:
OVERALL RESULT
Transformation of R-strain into S-strain was lost when DNA was destroyed by nucleases
Avery, MacLeod, McCarty Experiment:
Conclusion + Discovery
Conclusion = DNA of the S-strain bacteria is responsible for heritable changes during bacterial transformation
Discovery = DNA IS THE HERITABLE MATERIAL
Avery, MacLeod, McCarty Experiment:
Why did scientists not accept the conclusion/discovery of this experiment?
Scientists were skeptical
–> Concerned that some contaminating substance present in small amounts (that wasn’t DNA) was the actual transforming substance
= Debate continued until 1952
1952: Hershey
Alfred Hershey and Martha Chase Experiment
–> Studied bacteriophage replication, specifically which component actually entered the cell (insertion) and what was left outside of cell (shell)
Alfred Hershey and Martha Chase Experiment:
What bacteriophage was studied?
T2 Phage
–> A bacteriophage that infects E.coli
Virus
A little more than DNA (or RNA) enclosed by a protective, usually protein, coat
–> Take over cell machinery to produce more of the virus
Bacteriophage
A virus that infects bacteria
Alfred Hershey and Martha Chase Experiment:
Main question of the study
Which component (protein or DNA) was responsible for the ability to reprogram the host cell (into producing more virus)?
–> At this point in time, scientists knew viruses were made of protein and DNA but not which part was responsible for the reprogramming (AKA the heritable factor)
Alfred Hershey and Martha Chase Experiment:
METHODS
1) 2 batches of T2 were grown: one with a protein label and one with a DNA label
2) Each batch was mixed with E.coli –> Allowing infection
3) The phage-E.coli complexes were put into blender to separate shell from E.coli
4) Blended contents were centrifuged
5) Supernatant and pellet were tested for the radioactive labels (protein and DNA labels)
Alfred Hershey and Martha Chase Experiment:
What were the radiolabels utilized?
1) 35-S (radioactive sulfur) –> Protein Label
–> sulfur is a main building block of many proteins
2) 32-P (radioactive phosphorous) –> DNA label
–> phosphorous is part of the DNA phosphate group
Alfred Hershey and Martha Chase Experiment:
RESULTS
35-S was found in the SUPERNATANT (NOT in the E.coli cells)
–> Viral protein didn’t enter the cell
32-P was found in the PELLET (in the E.coli cells)
–> Viral DNA entered the cell
EXTRA RESULT:
–> After allowing phage replication to occur, the new phages had 32-P in them
Alfred Hershey and Martha Chase Experiment:
Conclusion + Discovery
Conclusion =
DNA injected by the phage into the host cell must be the molecule carrying the genetic information that makes cells produce new phages
Discovery =
DNA is the material of heredity!
1950: Chargoff
Erwin Chargoff
–> Nucleotide base compositional analysis study
–> Developed Chargaff’s Principle (evidence of base pairing)
Erwin Chargoff’s Study:
METHODS
1) DNA samples collected from different species
2) Separated DNA components by paper chromatography
3) Converted the separated components into mercury salts
4) Identified purines and pyrimidines by their UV light absorption spectra
Erwin Chargoff’s Study:
Results
1) Base composition of DNA varied from one species to another
2) In each species, the #A~#T and the #C~#G
Chargaff’s Rules
I. DNA base composition varies between species
II. For each species, the percentages of A is proportional to the percentages of T, and the same for C and G
Implications of Erwin Chargoff’s Study
1) Evidence of molecular diversity among species
2) Implied base pairing (A-T, G-C)
1953: 2 sets of scientists
–> Franklin + Wilkins
–> Watson + Crick
The data, experimentation, and studies conducted by these scientists led to the development of the double helix model of DNA
Franklin + Wilkins Work
Conducted X-Ray Crystallography on DNA
–> Produced an image showing the double helix shape of DNA with uniform diameter and geometries
X-Ray Crystallography
Franklin and Wilkins suspended a tiny fiber of DNA and then bombarded it with X-Rays for 100 hours of exposure
–> The X-Rays defract due to the electrons in the atoms of the fiber which then produces a pattern on a photographic plate
Watson + Crick Work
Built a model of DNA (double helix model) from Franklin’s diffraction findings, Chargaff’s rules, and other DNA research
1962: Watson + Crick
Win the nobel prize
