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Mutations of bacteriafrom virus sensitivityto virus resistance
S. E. Luria and M. Delbrück
Indiana University, Bloomington, Indiana, USA andVanderbilt University, Nashville, Tennessee, USA
May 20, 1943
Genetics 28(6):491-511.
Table of contents
1. Timeline2. The big Question3. Materials4. Methods(i) Laboratory(ii) Mathematics5. Results6. Aftermath(s)7. Discussion
Timeline
– 1859: Charles Darwin– The Origin of Species
– 1866: Gregor Mendel– Inheritence of factors in pea plants
– 1902: Walter Sutton– Chromosome pairs, Mitosis and Meiosis
– 1910: Thomas Morgan– The 'gene' theory
Timeline cont.
– 1928: Fred Griffith– Transformation
– 1944: Avery, MacLeod and McCarty– Transformation linked to DNA
The knowledge at the time
– Known:
– Species change and evolve under pressure.
– Inheritance follows certain rules.
– Cells contain substances called Protein and DNA
– Hypothesized:
– Inheritance is linked to DNA?
– Species change independent of pressure?
– Species change due to pressure?
Two models
Model 1: Directed mutations (DM). Individuals are susceptible to change at times.
Model 2: Spontaneous mutations (SM). Individuals change randomly at times.
The idea
– The two different models may result in different statistical properties.
– This difference may be significant and measurable.
Implications of the DM model
Number of cells at time t:
Let be the probability that a given cell is currently susceptible to change.
The number of susceptible cells in generation T is binomially distributed.
Thus,
0
T
n t =2t
p
Z ~ B n t , p~ B 2T , p
E Z =2T p , V Z =2T p 1− p
Implications of the SM model
Mutations in generation t:
Cells in T that originate from mutation in t:
Mutated cells in T:
0
T
t
X t ~ B 2t , p
Y T t = 2T− t X t
Z t = ∑t=1
T
Y T t
Implications of the SM model cont.
Mutations in generation t:
Cells in T that originate from mutation in t:
Mutated cells in T:
X t ~ B 2t , p
Y T t = 2T− t X t
Z = ∑t=1
T
Y T t
E X = 2t pV X = 2t p 1− p
E Y = 2T−t E X = 2T pV Y = 22T−t V X
E Z = ∑t=1
T
E Y
= T 2T p
V Z = ∑t=1
T
V Y
= 22T1−12T p 1− p
Measurable property
– DM model – SM model
E Z =2T p
V Z =2T p 1−p
V Z E Z
= 1− p ≈ 1 V Z E Z
= 2T−11− p T
≫ 1
E Z = T 2T p
V Z = 22T1− 12T p 1− p
Experimental results
Figure: Histogram of the number of resistant bacteria, as observed in 87 parallel cultures (black bars), and corresponding distribution expected under directed mutation (white bars).
The aftermath(s)
– 1952: Hershey & Chase– Final proof that DNA is the genetic material.
– 1969: Delbrück, Hershey and Luria are awarded the Nobel prize in Medicine.
– Their method is used until today under the name 'fluctuation test'