1. Intro to microbial evolution

2. Goal of this video lecture
Teach you about the processes that govern the rate of microbial evolution

3. Antibiotic resistance evolution on video
Roy Kishony’s lab at Harvard
What happens when populations are exposed to low, but increasing levels of antibiotic for long periods of time?

4. Evolution: definition and processes
Change in gene frequency over time in a population
New mutations
New variation
Migration – of individuals
Spreading variation
Horizontal gene transfer
Genetic drift

5. Natural selection
If: Heritable variation among individuals in a feature
And: A positive relationship between that feature and survival and reproduction ability (fitness)
Then:
The frequency of that feature in the population across generations will be predictably different from what could be expected by chance
***Natural selection is by definition non-random and therefore theoretically predictable

6. How fast can antibiotic resistance evolve within a population
How fast can antibiotic resistance evolve within a population? (a patient?)
What we are going to do right now, is talk about how the evolutionary process plays out in microorganisms, and we are going to consider a specific case.
How does antibiotic resistance evolve within a population? Let’s imagine a patient being exposed to relatively low amounts of antibiotics. It imposes a cost on the fitness of the microbe, causing it to expend energy or modify its structures to minimize damage, but does not necessarily kill all of the microbes outright. How would the population evovlve?

7. How fast can antibiotic resistance evolve within a population
How fast can antibiotic resistance evolve within a population? (a patient?)
Simple conditions
Initially clonal population (all cells exactly same genotype)
No HGT
No migration
So, genetic diversity = 0
Genetic variation comes from new mutation
We are going to start with a simple case, where the population is clonal, and there is no possibility of HGT or migration. The only source of new genetic variation is new mutation.

8. Step I. Generation of new genetic variation
How long until we get genetic variation?
Mutation supply rate = mutation rate*population size
E. coli stats: mutation rate = ; population size for this thought experiment: 1e8 *
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Generations X
The mutation rate is per genome per generation. It is the genome-wide mutation rate.

9. Step I. Generation of new genetic variation
Mutation supply rate = mutation rate*population size
E. coli stats: mutation rate = ; population size for this thought experiment: 1e8
Possible mutation effects:
Beneficial
Neutral
Deleterious *
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Generations X

10. Step II. Mutation escapes genetic drift
Probability of loss by genetic drift ~ 2S in a large population
S = difference between mutant genotype and average fitness (W) of population
. Is about 2S in large population
S= difference between mutant genotype and average fitness of population LOOK THIS UP IN A SMALL POPULATION

11. Step II. Mutation escapes genetic drift
Probability of loss by genetic drift ~ 2S in a large population
S = difference between mutant genotype and average fitness (W) of population
. Is about 2S in large population
S= difference between mutant genotype and average fitness of population LOOK THIS UP IN A SMALL POPULATION *
* *
Generations X

12. Step III. Mutation increases in frequency by natural selection
Initial frequency = 1/N, N = population size
N = 1e8 cells
How long does it take to become dominant: 50% of population?
Tau = generations until it reaches a particular frequency in population
Tau = log2 (0.5N)/S
Initial frequency is 1/N, N=population size
How long does it take to become dominant in population?
Tau is approximately = log2 (0.5N)/S cell generations to get to 50% frequency in population
If S is large, Tau is small, so cell generations is small. Tau is larger if N is larger.
Thus, large effect beneficial mutations will rise to fixation faster than small, and mutations will become fixed faster in smaller than larger populations.
The numerator is basically the number of divisions that must occur, and it is divided by the advantage (or disadvantage) of the mutant relative to the rest of the population.

13. Step III. Mutations rise in frequency by natural selection
Initial frequency = 1/N, N = population size
N = 1e8 cells
How long does it take to become dominant: 50% of population?
Tau = generations until it reaches a particular frequency in population
Tau = log2 (0.5N)/S
Initial frequency is 1/N, N=population size
How long does it take to become dominant in population?
Tau is approximately = log2 (0.5N)/S cell generations to get to 50% frequency in population
If S is large, Tau is small, so cell generations is small. Tau is larger if N is larger.
Thus, large effect beneficial mutations will rise to fixation faster than small, and mutations will become fixed faster in smaller than larger populations.
The numerator is basically the number of divisions that must occur, and it is divided by the advantage (or disadvantage) of the mutant relative to the rest of the population. *
* *
Generations X

14. Selective sweep *
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Generations X

15. Selective sweep
Is the process this simple? In the video, did we see a selective sweep like this? *
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Generations X