Lecture 5: Population Genetics: How do variations get fixed in

populations via natural selection? KEY QUESTIONS related to genetic variation

1. Birth of Population Genetics •How do allele frequencies change over time in the
2. Hardy_Weinberg principle absence of natural selection and other evolutionary
processes?
3. 4 Main Processes of Population Genetics
• How do we build a mathematical model for natural
a) Selection
selection?
b) Drift
• How do mutation, non-random mating, and migration
c) Mutation affect genotype and allele frequencies in a population?
d) Gene Flow
4. Other Processes
• Non-Random Mating KEY TERMS

• Population genetics • Hardy–Weinberg model • Hardy-

Weinberg equilibrium • Directional selection •
1. Birth of Population Genetics Frequency-independent selection • Frequency-
dependent selection • Overdominance/underdominance
- A discipline that moves beyond predicting genotype • Positive/negative frequencydependent selection •
frequencies between pairs of organisms (individual) Balancing selection • Mutation-selection balance
that reproduce (with Punnett squares, etc)
Learning Outcomes
➢ to predicting genotype frequencies of whole
populations across generations • Understand how variations are fixed in populations via
- Population genetics is the study of how natural selection (Directional selection)
The 4 main processes affect allele frequencies in
• Explain broadly how population genetics developed as a
populations
science and what it is used for (1. Birth of Population Genetics)
• Type of questions addressed by
• Explain Hardy–Weinberg equilibrium and its
population genetics
implications (2. Hardy Weinberg Principle)
- Do dominant or recessive genes spread at different
rates in a population if advantageous? • Understand the four main processes of population
- How quickly might we expect bacteria to evolve genetics (plus random mating)
antibiotic resistance? • Explain types of natural selection (3. 4 main processes of
- Can we estimate the ages of different species? Population Genetics)

• Able to do basic population genetics calculations from

2. Hardy Weinberg principle Chapter 7 in the textbook, with an emphasis on those
• proposed a null model of what happens to models mentioned in the lecture slides
alleles over time in a population with the
following assumptions:
1. no natural selection

2. no genetic drift (infinite populations)

3. no mutation

4. no migration or gene flow

RECALL:
 5. random mating where individuals mate

randomly with each other

A) Formula
• Let the frequencies of the three genotypes A1A1, A1A2, and A2A2 be f[A1A1], f[A1A2,] and f[A2A2]
- f[A1A1] + f[A1A2,] + f[A2A2] = 1
• Let p be the frequency of the A1 allele & Let q be the frequency of the A2 allele:

• What are the frequencies of [A1A1], [A1A2] and [A2A2] genotypes in the next generation

Probability of drawing gamete A1 with frequency p twice in a row

probability of drawing gamete A2 with frequency q twice in a row

P() + P() + probability of drawing A2 first and then drawing A1 = p x q + q x p = 2pq

- Important point: The frequencies of [A1A1], [A1A2] and [A2A2] genotypes in the next generation, p2, 2pq, and
q2, depend only on the original allele frequencies not on the original genotype frequencies
• Hardy – Weinberg Equilibrium Frequencies

➢ Thus, no reason to expect a dominant character (A1A1) to spread in a population: this character
appears in a population relative to the frequency of its causative allele (p)
• Where did Yule and his colleagues go wrong? Why did they think a dominant character would
spread in a population
- They confused the idea of dominance with the ideas of transmission and fitness:
➢ Dominance relates to gene expression: a dominant allele is always expressed
➢ There is no reason to think a dominant allele would be more fit than a recessive allele

B) Conclusion:
- resolved concerns of Yule et al. that dominant alleles would spread
- provided a means of testing whether strong selection or other forces were acting at particular genetic loci
- showed how genetic variation can easily be maintained in a population over time (noted by Fisher). This solves
one of the central paradoxes of Darwin’s theory

C) Case Study: Human Myoglobin

• Genotype frequencies will hardly ever exactly match the Hardy-Weinberg frequencies. Why?
- If allele frequencies don’t match the Hardy–Weinberg frequencies, one or more of these assumptions
must have been violated
➢ It tells us that populations are evolving
- How do we test if the deviations from Hardy–Weinberg frequencies are important?
• Use a statistical test (chi-square test)
- χ2 = ∑(Oi – Ei )2/Ei
- Oi = number of individuals observed in each genotype (A1A1, A1A2, and A2A2) Ei = number individuals expected
to observe in each genotype under HardyWeinberg equilibrium Researchers took the blood samples from 100
Japanese volunteers. Test for HardyWeinberg equilibrium using chi-square test.
➢ χ2 = 0.157
➢ Reject or accept null hypothesis ? Commented [ATSH1]: Watch lecture to find out

3. 4 Main Processes of Population Genetics

A) Natural Selection
- Acts when the environment favours some alleles over others
- Acts on phenotypes and this indirectly affects allele frequencies
- Can affect viability (survival) or fecundity (reproduction)

• Types of natural selection on a single locus

• Frequency-INdependent selection:
- genotype fitness do not depend on their current frequencies in the population
o Directional selection
o Overdominance
o Underdominance
• Frequency-DEPENDENT selection:
o Positive frequency-dependent selection
o Negative frequency-dependent selection
• Case study: Pocket Mice (Directional Selection)
- Coat colour is influenced by alleles at the melanocortin-1 receptor
- 2 alleles: call them D (dominant) and d (recessive)
• How does natural selection act on coat colour in populations?
- On dark lava fields, survival of light-coloured mice is lower
than dark mice
➢ This suggests that light-coloured mice have lower fitness than darkcoloured
mice on dark lava fields
• How does this affect the frequencies of the D and d alleles
and the frequencies of the three genotypes?
• Selection Coefficient (s)
• s is expressed and has a value between 0 and 1
- If s = 1, selection against the genotype is total, and it makes no contribution to the next generation
- If s = 0, the genotype is not selected against at all
Dark Lava Fields Light - coloured mice Dark - coloured mice
Survival of 60 – 98% 100%
Fitness 1 – 0.4 = 0.6 to 1 – 0.02 = 0.98 1.0
Selection Coefficient [Against] 0.02 – 0.4 (2 - 40%) 1
- Let’s arbitrarily set the survival of the dark-coloured mice at 1 and that of the light-coloured-mice be 1−s
➢ Then, based on the survival data, s is in the range 0.02 to 0.4
• Let’s now build a model where different genotypes can have different values of fitness in this way:
- Use A1 and A2 instead, as we did in the Hardy–Weinberg model
- Modify the basic Hardy–Weinberg model by relaxing the assumption that
there is no natural selection:
➔ i.e. assuming that survival of A2A2 (light-colored mice) every generation
o is only a fraction 1−s that of the other two genotypes,
➔ i.e., individuals with genotype A2A2 are less fit
➢ Still assuming random mating, so the genotype frequencies will initially
be as predicted by Hardy–Weinberg

*NOTE*
• We assumed selection affects survival here, but we could have introduced selection into the model in other
ways by, e.g., allowing selection to affect reproductive output instead
• We arbitrarily set the default genotype fitness to 1. We could have chosen some other value. It is the ratio of
the fitnesses that matters here
• We chose to modify only one genotype fitness from the default. We could have modified more than one.
• The frequencies after selection don’t add up to 1 anymore! This is a problem that we can correct by
normalising…
• Model of Frequency-Independent Selection

• Modes of Allelic Interaction

• Thus far we have considered Mendel’s recessive–dominant mode of two-allele interaction, where the
heterozygote phenotype is the same as the dominant homozygote phenotype (A1 allele is dominant; A2 is
recessive)
- But the real situation can be more complicated:
➢ Heterozygous phenotype intermediate: incomplete dominance (A1 allele is co-dominant)
➢ Phenotype of heterozygote lies outside the range of the two homozygotes: can lead to overdominance or
underdominance
• How are variations fixed (p: frequency of an allele reaching 1) in populations via natural selection
o Directional selection: leads to allele fixation
1) Complete dominant/recessive case
a) with the favoured allele A1 dominant

b) with the favoured allele A1 recessive

- Now the allele frequency increases much more slowly at first, but faster when it escapes rarity
2) Incomplete dominance has different dynamics
 Directional selection
with different types of
allele

• Models like these can be used to understand and predict the population genetics of pocket mice
- The D allele is dominant, and on dark lava fields darkcoloured mice are fitter
- But on light-coloured rocks, light-coloured mice are fitter
• Overdominance:(when heterozygotes are fitter) leads to stable polymorphisms

• Underdominance: (when heterozygotes are less fit) leads to allele fixation

• Positive frequency-dependent selection:
- fitness associated with a trait increases when the trait is more common
➢ leads to fixation of one allele

• Negative frequencydependent selection

- fitness associated with a trait decreases when the trait is more common

- Examples:
• Traits associated with the immune system are often under negative frequency-dependent selection
➢ If every individual in a population has a similar immune system, the population is vulnerable to disease, so rare
traits are favoured
 B) Mutation
- It is straightforward to analyse simple population genetics models
with mutation, e.g., a model with two different alleles A1 and A2
in which mutation in both directions is possible
- Mutation rates are typically denoted by the symbols μ and ν
• Mutation-selection balance
• We can also devise and analyse population genetics models with selection and mutation
- An application of such models is to study the dynamics of rare genetic diseases. For example, consider a disease:
➢ that arises from a rare mutation at a single locus
➢ that is harmful but not fatal and therefore selection is fairly weak against this mutation
- So
➢ Mutation is generating the allele
➢ But selection is acting against it
➢ We expect the frequency of this disease to be in some equilibrium balance in the population – never really
disappearing
C) Gene Flow
• involves the movement of genes through space
- e.g., Island – mainland model
➢ where immigrants disperse from the mainland to the island
➢ gene flow is likely the only important process affecting allele frequencies (i.e., we will ignore selection, drift and
mutation)
• Gene flow tends to equalize allele frequencies in populations over time
- For example, consider the case where the allele A1 initially has frequency pi =0.2 on the island and frequency
pm=0.7 on the mainland, and where the immigration rate is k=0.1

• Summary of the mechanisms of Evolution

4. Other Processes
• Non-Random Mating
- affects genotype frequencies and can influence selection but, on its own, does not affect allele frequencies, so it
is not usually considered one of the main processes
A) Assortative mating
• individuals mate with others of the same genotype
- Flat snails exhibit assortative mating (and in this case, as we saw
earlier, non-random mating leads to frequency-dependent selection
- Humans also mate assortatively, e.g., for height
• Inbreeding: assortative non-random mating
- Occurs when individuals mate with close genetic relatives
- Inbreeding on its own does not change allele frequencies, although it does change genotype frequencies (more
homozygotes
- Inbreeding depression occurs if homozygotes are less fit, often because of rare recessive deleterious alleles that
are identical by descent
B) Disassortative mating
• individuals mate with others of different genotypes
• Examples:
- White-throated sparrows: white-striped birds prefer to mate with tanstriped birds
- Humans show a preference for mates with different major histocompatibility complex genes: this promotes
heterozygosity and greater pathogen resistance in offspring