Lecture 6: Genetic drift: How do variations get fixed in populations

via natural selection? KEY QUESTIONS related to genetic

variation
1. Genetic Drift
2. Population Bottlenecks • How different is the process of evolution
between small and large populations?
3. Founder Effects
• How does genetic drift work, and what are its
4. Drifts & Selection consequences?
5. Natural Theory of Molecular Evolution • How do demographic processes such as
6. Molecular Clocks population bottlenecks and the founder effect
contribute to evolutionary change?

• What happens when genetic drift interacts

with mutation and selection?
1. Genetic Drift
• Definition:
- refers to allele frequency changes due to random sampling effects
(or sampling errors in the production of zygotes from a gene pool) KEY TERMS:
in finite populations that have no impact on fitness Genetic drift • Population
➢ can cause changes in allele frequencies, but cannot produce adaptation bottleneck • Founder
effect • Effective
population size •
Heterozygosity • Wright’s
F-statistic • Positive
selection • Purifying
• The vagaries of chance selection • Neutral
• In each generation, some individuals may, just by chance, leave behind a few more theory • Molecular clock
descendants (and genes!) than others
- The genes of the next generation will be the genes of the ‘lucky’ individuals,
not necessarily the healthier or ‘fitter’ ones
➢ It affects the genetic makeup of the population but, unlike Learning Outcomes:
natural selection, through an entirely random process
• Drift Simulations
• simulator
- What is the chance of a particular allele with starting frequency (0.5)
to become fixed in a population?
a) Population size 30, 100 generations, allele frequency 0.5
b) Population size 15, 100 generations, allele frequency 0.5
➢ Probability of fixation of an allele will be affected by population size
- Is drift a stronger evolutionary force in small or in large populations?
a) Population size 1000 vs 30, 100 generations, 0.5
➢ Drift is a stronger evolutionary force in small populations
- What is the probability of fixation of an allele initially present at 0.1,0.3 & 0.8 frequency in a population?
➢ 0.1, 0.3, 0.8
• Observations
- Direction of allele frequency is random, unpredictable
- Fixation of alleles occurs faster in small populations
 - Fluctuations are more pronounced in small populations, so drift has a stronger effect in these
populations
- Predicting the outcome of an individual simulation: probability of fixation for an allele is proportional
to its frequency; probability changes during drift
• Visual Representation of Genetic Drift
- Suppose that we have a population of N = 16 individuals, each of which has 2 allele

Initially there are After just one or After a longer

50% A1 alleles two generations of period of time,
(red) and 50% A2 random mating, one of the alleles
alleles (blue) the allele may come close to
frequencies will fixation
*The population size doesn’t change from one generation
probably todiffer
the next
slightly from 50–
• “forward looking” probabilistic model50of Wright–Fisher of population genetics
- Drift can occur (finite population size), but assumes:
• No selection • No mutation • No gene flow (migration) • Random mating • Constant population size (N)

- What happens to heterozygosity (frequency of A1A2 genotypes) over time?

➢ Heterozygosity is at max level with A1 = 0.5 and A1 = 0.5, so when either allele goes to fixation,
heterozygosity of populations decreases.
• Genetic Drift: Conservation
- Small populations of plants and animals (including humans) can be at risk because of reduced genetic diversity
➢ This has implications for conservation strategies
- Examples of such animals include:
• How can we quantify the effects of drifts in populations?
A) Heterozygosity H
B) Wright’s F-statistic FST
- expected degree of a reduction in heterozygosity when compared
to Hardy–Weinberg expectation
- Sometimes called fixation index
• Heterozygosity declines when drift occurs in
small populations
- Every population has a different trajectory for heterozygosity, but
all decline
- The average (grey) is however closer to the expected decline
from theory (purple)
• Loss of genetic diversity in small populations
A) Heterozygosity H (Wright-Fisher model)
- Let Ht be the heterozygosity (frequency of heterozygotes) at time t. The expected heterozygosity in generation t

is , N: population size
- The value of (1– 1/2N) is always between ½ and 1
➢ Thus, expected heterozygosity is declining over time—
genetic diversity is lost through drift
➢ The smaller the population size N, the faster the genetic diversity
will be lost
- Let’s verify the mathematical formula by comparing it to the results
of simulations

Population size = 32 Population size = 1000

Fairly stochastic, A1 goes to fixation in some Everything is more stable • Drift has weaker
populations. Heterozygosity decreases fast effects in large populations
 B) Wright’s F-statistic
- Wright’s F-statistic can be calculated from the degree of heterozygosity in a population. In our two-allele
example, the F-statistic can be calculated as

• where “Expected” means the expected frequency at Hardy– Weinberg equilibrium

• Analyzing the effects of drift
- we will take the expected heterozygosity to be the heterozygosity in generation 0, which we referred to earlier
as H0

- We already have a formula predicting the observed heterozygosity

- Putting these together gives

➢ Expected value of Wright’s F-statistic after t generations of random mating in a finite diploid population of size
N: F = 1 – (1 – 1/2N) ^ t
➢ Here we are guaranteed F≥0
➢ In fact, for this problem, F can be interpreted as the probability that the two gene copies at a locus in a single
individual are identical by descent, i.e., descended from the same ancestor in generation 0

• What is the effect of drift on small populations of the same species that live in different
locations?
A) Islands of Randomness
- Imagine that we have several islands each of which contains a population of a species with initially exactly the
same population genetic structure
• What will happen in the long term to the genetic composition of these populations?
➢ If we assume there is no selection, mutation, or migration, then the only process is drift, which will cause the
populations to diverge in their genetic structure over time
➢ Eventually, one allele will become fixed on each island, although it may not be the
Same allele on every island

→→→→→
- Because of the randomness inherent to the drift process,
the outcome will not be the same every time
2. Population Bottlenecks
• Refers to a rapid decrease in population size
- Initially, each population has N = 1000 individuals,
but N is temporarily reduced to 10 individuals for generations 90–99
➢ The brief period of small population size, or bottleneck leads to
drastic shifts in allele frequencies

• Bottlenecks: Genetic diversity will usually be lower after a bottleneck

- For example, in 1/4 populations the focal allele has gone to fixation
after the bottleneck
• Increasing Population Size
- Here each population starts with N = 10 individuals but then gradually increased
to N = 1000 individuals
➢ Variability between populations now greater than in the case of N = 1000 constantly

3. Founder Effects
• Definition
- One scenario in which increasing population size occurs is when there is a
founder effect
➢ The resulting population will usually have lower genetic diversity than the source
(mainland population) and the genetic composition will vary across different islands colonised in this way
• When new founding populations carry only a sub-set of the original population

• Calculating Effective Population Size, Ne

- Required to adapt our mathematical results to the scenarios with fluctuating population size
- the size of an idealized Wright–Fisher population that would lose heterozygosity at the same rate as an actual
population of interest

- For a fluctuating population over T generations we have

- Here each population starts with N = 10 individuals, but this is then
gradually increased to 1000 individuals
➢ The effective population size Ne here is ≈ 323
• Note that this is much lower than the average population size (753)
4. Drifts & Selection
• Fixation of alleles will happen faster with selection
• In small population deleterious alleles can be fixed
• Advantageous alleles can go extinct
• What happens if drift and selection are occurring simultaneously?
A) Fixation
- of initially rare but selectively favoured allele likely for:
• Large population size (Ne) • Large selective advantage (s)
➢ Selection dominates
B) Extinction
- of initially rare but selectively favoured allele likely for:
• Small population size (Ne) • Small selective advantage (s)
➢ Drift dominates
• Kimura’s (1983) rule of thumb: • when s ≫ 1/2Ne: SELECTION dominates • when s ≪ 1/2Ne: DRIFT dominates
• Connecting populations to species: Eventually species differences result from the collection of
these fixed alleles?
- Is most of the genetic variation we see in real populations due to drift or selection?
➢ Since the 1960s, molecular techniques have revealed a large amount of genetic variation in populations—more
than could easily be explained by natural selection

5. Natural Theory of Molecular Evolution

- Many mutations do not lead to any change in proteins because of the degeneracy of the genetic code
- Many of these mutations form the basis for a “molecular clock”
➢ Mutations that do not lead to any change in protein encoding are called synonymous substitutions

6. Molecular Clocks
- Nucleotide substitution appears in many cases to proceed at a roughly constant rate
- Hypothetical example:

➢ In this hypothetical case, we get about one substitution every 2m years, so two species that diverged 2m years
ago should have roughly 2 nucleotide differences
• Effects of population genetic processes

Take-home messages
• In finite populations, allele frequencies fluctuate as results of random sampling effects, i.e.,
genetic drift

• Drift operates more strongly in small than large populations

• Drift reduces heterozygosity (H and Wright’s F-statistic)

• Drift causes divergence between populations over time

• Population bottlenecks and founder effect changes in allele frequencies