Intro to microbial evolution

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

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? https://www.youtube.com/watch?v=Irnc6w_Gsas

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

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

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?

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.

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 = 0.0002; population size for this thought experiment: 1e8 * * * 0 Generations X The mutation rate is per genome per generation. It is the genome-wide mutation rate.

Step I. Generation of new genetic variation Mutation supply rate = mutation rate*population size E. coli stats: mutation rate = 0.0002; population size for this thought experiment: 1e8 Possible mutation effects: Beneficial Neutral Deleterious * * * 0 Generations X

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

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 * * * 0 Generations X

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.

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. * * * 0 Generations X

Selective sweep * * * 0 Generations X

Selective sweep Is the process this simple? In the video, did we see a selective sweep like this? * * * 0 Generations X

https://www.youtube.com/watch?v=Irnc6w_Gsas