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Natural
Selection
Natural Selection
An Adaptive Mechanism
Evolutionary Mechanisms
Genetic Drift
Migration
Non-adaptive
Mutations
Natural Selection
Adaptive
Darwin
Evolution acts through
changes in allele frequency
at each generation
According to Darwin, this
happens via
Natural Selection
(He considered Selection only, and not
other evolutionary mechanisms, such as
mutations, genetic drift, etc.)
Sources of Genetic Variation
Mutation generates
genetic variation
Natural Selection
Natural Selection acts on
genetic or epigenetic
variation in a population
Epigenetic modification
changes expression of
genes
Genetic Drift can reduce
genetic variation
Without genetic or
epigenetic variation,
Natural Selection cannot
OUTLINE
(1) General Description of Natural Selection
(2) Modes of Natural Selection
(3) Selection Violating Hardy-Weinberg
Equilibrium
Darwin’s contribution:
Population Speciation as a result of Natural Selection

Too many offspring produced
Limited resources and competition

Variation in a population

Better adapted individuals survive

Survivors leave more offspring

Thus, average character of population is altered

Natural Selection
The differential survival and/or reproduction of
classes of entities that differ in one or more
characteristics
The only evolutionary force that is ADAPTIVE
NOT random, but deterministic
Darwin

Population speciation
Darwin

Population speciation
mutation
Darwin

Population speciation
Selection
favors
Darwin

Population speciation
Greater
Fitness
Selection on pathogens imposed
by Drugs (refer to Lecture 1)
AZT



AZT (Azidothymidine) is a thymidine
mimic which stops reverse transcription
Mutations in the reverse transcriptase
gene of HIV arises such that the enzyme
can recognize AZT
The drugs impose Selection on the virus.
Genetic variation (generated by
mutations) allows the virus to respond
to selection and evolve drug resistance
Selection imposed by Transmission Rate
on Virulence of HIV



Need to keep host alive long enough to get passed
on to the next host
(Tradeoff between fast population growth and keeping
the host alive)
High Transmission rate : High Virulence
(Can grow fast and jump to the next host; ok if host dies;
genetic strain that grows faster will win)
Low Transmission Rate : Low Virulence
(More virulent strains would die with the host and get
selected out; less virulent strain will win)
High Transmission Rate
If the virus is likely to move to a new host the faster
growing (and more virulent) strain is likely to
overtake the slower strains and “win”

It’s ok to kill the host, since the chances of jumping
to a new host is high


Natural selection will favor the more virulent strain
Low Transmission Rate
If the virus is not likely to move to a new host the
slower growing (and less virulent) strain is likely to “win”

It’s not ok to kill the host, since the chances of
jumping to a new host is low. If the virus kills the host,
it will kill itself


Natural selection will favor the less virulent strain
Evolution of HIV resistance in Human Populations





CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a mutant
allele of the receptor CCR5, where the deletion of a 32 base
pair segment makes the receptor nonfunctional
The allele has a negative effect upon T cell function, but
appears to protect against smallpox and HIV
HIV has no receptor to bind to and cannot enter the cell
This allele is found in 14% of Europeans
HIV can impose selective pressure for CCR5-Δ32, increasing
the frequency of this allele in human populations (Sullivan et
al. 2001)
Amy D. Sullivan et al. 2001. The coreceptor
mutation CCR5Δ32 influences the dynamics
of HIV epidemics and is selected for by HIV.
Proc Natl Acad Sci USA. 98: 10214–10219.
Frequency shift in CCR5- D32 allele
Fr
Modes of Selection
Selection on discrete vs
continuous characters

When phenotypes fall into discrete classes (like
Mendel’s yellow vs green peas), we can think of
selection acting directly on genotypes
 Such
discrete traits are usually coded by one or a
few genes (loci)

However, when phenotypes fall into a
continuum (continuous traits such as those
Darwin examined, beak shape, body size), you
will see changes in the distributions of traits
(next slide) –such traits are called “quantitative traits,”
coded by many loci
DIFFERENT MODES OF SELECTION
(Herron & Freeman Section 9.6)
Directional Selection
on a discrete trait
Directional Selection
on a continuous trait
Directional
Selection:
Selection changes
frequency of alleles
in one direction
die
shift in distribution
Directional Selection:
Selection changes frequency of
alleles in one direction
Mock Example
Directional Selection on a discrete trait
Generation 1
Generation 2
.
.
.
Generation X
AA
0.80
0.60
.
.
.
0.04
Aa
0.15
0.30
.
.
.
0.16
aa
0.05
0.10
.
.
.
0.75
Directional Selection
on a discrete trait
Directional Selection
on a discrete trait

How will selection act if A is
dominant and selection favors
red?
AA

aa
How will selection act if A is not
dominant, but Aa intermediate?
AA

Aa
Aa
aa
Under which situation will the “a”
allele be preserved in the
population longer?

How will selection act if A is
dominant and selection favors red?
AA
Aa
aa
Selection will act on AA and Aa in the same
manner

How will selection act if A is not
dominant, but Aa intermediate?
AA
Aa
aa
Selection will act more strongly on AA

Under which situation will the “a”
allele be preserved in the population
longer?
The first above, as the “a” allele is more
effectively masked in the heterozygote state
Directional Selection
on a discrete trait
Selection on Dominant vs Recessive Alleles



Herron & Freeman
Selection against recessive allele
Set fitness of genotypes to:
WAA = 1, WAa = 1, Waa = 1 – s
(s = selection coefficient)
Selection against dominant allele
Set fitness of genotypes to:
WAA = 1 - s, WAa = 1 - s, Waa = 1
(AA and Aa have same phenotype)
Selection on Dominant vs Recessive Alleles



What Happens?
Selection against recessive allele
In Allele A1, set fitness of genotypes to:
WAA = 1, WAa = 1, Waa = 1 – s
(s = selection coefficient)
Selection against dominant allele
Set fitness of genotypes to:
WAA = 1 - s, WAa = 1 - s, Waa = 1
(AA and Aa have same phenotype)
Selection on Dominant vs Recessive Alleles

Selection against recessive allele:
 As
recessive allele becomes rare, rate of its
disappearance slows down
 As homozygote recessive allele becomes
rare, most are in the heterozygous state and
are masked from selection

Selection against dominant allele:
 Dominant
allele that is disfavored by selection
is removed quickly from the population
Directional Selection:
Selection changes frequency of
alleles in one direction

Genetic diversity is reduced
(knock out maladapted genotypes)

Examples:



Drug-resistance in tuberculosis and
HIV
Agriculture: artificial selection for
specific traits
Sexual selection for a trait (e.g. for
bright plumage)
Directional Selection
Directional Selection during Domestication



Rapid evolution under
intense directional
selection for large and
numerous kernals
Selection by humans for
a few regulatory genes
(affecting transcription)
Reduced genetic
diversity in domesticated
corn
Morphological differences between teosinte and
maize

Maize with tb1
knocked out
• Has
branching
patterns like
teosinte
maize
teosinte
Corn
Genes selected for in Corn
F1 Hybrid
Teosinte
Major morphological difference
are due to directional selection
on 5 genes
Genes:
• Teosinte branched1 (tb1): single
mutation affects branching and
inflorescence
• Regulator of tb1
• tga glume (outer coating) reduction
on chromosome X
• teosinte – ~8-12 kernels
F1 hybrid 8 rows, corn 20+rows
Evidence for selection in 2-4%
genes, ~1200 genes
Hardy Weinberg revisited
Generation 1
Generation 2
Generation 3
AA
Aa
aa
250
750
900
500
200
90
250
50
10
(1) Is this population remaining in HW Equilibrium
from generation to generation?
(2) What might be going on?
Hardy Weinberg revisited
Generation 1
Generation 2
Generation 3
AA
Aa
aa
250
750
900
500
200
90
250
50
10
(1) Is this population remaining in HW Equilibrium
from generation to generation?
***check if (a) alleles frequencies change across generations
and (b) whether the allele frequencies do not yield the
predicted genotype frequencies
(2) What might be going on?
AA
Aa
Generation 1
250 (freq = 250/1000)
500
Generation 2
750 (freq = 750/1000)
200
Generation 3
900 (freq = 900/1000)
90
First convert # of individuals to frequency of genotypes
aa
250
50
10
(1) Is this population remaining in HW Equilibrium from generation to
generation? NO
Gen1
Freq of A (p) = 0.25 + (0.50/2) = 0.50
Freq of a (q) should be = 1 -0.50 = 0.50
Gen2 Freq of A (p) = 0.75 + (0.20/2) = 0.85
Freq of a (q) = 1-0.85 = 0.05 + (0.20/2) = 0.15
Gen3 - can do same calculations
**Allele and genotype frequencies are changing across generations: freq of A
is increasing across the 3 generations
**Genotype frequencies deviated from expectations based on allele
frequencies: freq of A is 0.5 in Gen1, so expect AA =0.25 at Gen2,
(2) What might be going on? Directional selection favoring A?
Hardy Weinberg revisited
AA
Aa
aa
0.44
0.56
0
(1) Is this population in HW Equilibrium?
(2) Are the HW expectations the same as the
genotype frequencies above?
Hint: Calculate the genotype frequencies from the #
above, and then calculate allele frequencies. Use the
allele frequencies to calculate HW expectations.
(3) What might be going on?
Hardy Weinberg revisited
AA
Aa
aa
0.40
0.60
0
(1) Is this population in HW Equilibrium? NO
(2) Are the HW expectations the same as the
genotype frequencies above? NO
Freq of A (p) = 0.40 + (0.60/2) = 0.70
Freq of a (q) should be = 1 - 0.70 = 0.30
Based on HW expectations, freq of aa should = 0.3 x 0.3 =
0.09
aa is missing!  Negative selection acting against aa?
aa might be a homozygous recessive lethal
Stabilizing Selection (on discrete or continuous traits)
die

Selection acts against the extremes
(favors intermediate trait) =purifying
selection

The average trait value stays the
same

Genetic diversity is reduced

This is going on all the time, as
deleterious alleles are getting
selected out of the population

Examples:
Selection against new harmful mutations
Selection for an optimal number of
fingers
Selection for optimal body size
Example of Stabilizing Selection
Selection for an
optimal number of
eggs
Disruptive Selection (on discrete or continuous
traits)

Selection favors the extremes

Genetic diversity is increased (help
maintain genetic variation; knock out
alleles that code for intermediate traits)

Can lead to formation of new species

Examples:




Niche Partitioning (Specialization on
different resources, food)
Differences in habitat use
Will discuss more in lecture on
Speciation
Sexual selection for different traits
(blue birds mate with blue, red birds
mate with red)—intermediate colors
selected against
Disruptive Selection
Balancing Selection
(on discrete or continuous traits)

Balancing Selection is a generic term to refer to any type
of selection that acts to maintain genetic variation in a
population

There are different mechanisms: Fluctuating selection,
selection favoring heterozygote (=overdominance)

Examples:



Selection for heterozygotes (sickle cell anemia, and cystic
fibrosis)
Selection for different traits in different environments
Selection for different traits at different times (fluctuating
selection)
Balancing Selection

An Example of one mechanism:
Overdominance: Selection favoring the
heterozygote
Generation 1
Generation 2
Generation 3
AA
0.25
0.20
0.10
Aa
0.50
0.60
0.80
aa
0.25
0.20
0.10

Genetic diversity is maintained in a population in
this case because the heterozygote maintains both
alleles

Example: Sickle Cell anemia
Balancing Selection

An Example of one mechanism:
Overdominance: Selection favoring the heterozygote
Generation 1
Generation 2
Generation 3
AA
0.25
0.20
0.10
Aa
0.50
0.60
0.80
aa
0.25
0.20
0.10

In this case, allele frequencies (of A and a) do not
change. However, the population did go out of HW
equilibrium because you can no longer predict
genotypic frequencies from allele frequencies

For example, p = 0.5, p2 = 0.25, but in Generation 3,
the observe p2 = 0.10
Balancing Selection

An Example of one mechanism:
Overdominance: Selection favoring the heterozygote
Generation 1
Generation 2
Generation 3
AA
0.25
0.20
0.10
Aa
0.50
0.60
0.80
aa
0.25
0.20
0.10

Genetic diversity is maintained in a population in this
case because the heterozygote maintains both alleles

Example: Sickle Cell anemia
Balancing Selection

An Example of one mechanism:
Overdominance: Selection favoring the heterozygote
Generation 1
Generation 2
Generation 3

AA
0.25
0.20
0.10
Aa
0.50
0.60
0.80
aa
0.25
0.20
0.10
Why is this NOT stabilizing selection? In
Stabilizing Selection genetic diversity decreases
as the population stabilizes on a particular trait
value (a quantitative trait, like body size, height,
intermediate color –of a multilocus nature)
Sickle cell anemia
example of balancing selection


Reduced ability of red blood cells to carry oxygen
(mutation in HbS gene, makes defective hemoglobin
protein)
HAHA: homozygous, no effects of disease (sickle cell
anemia)

HAHs: heterozygotes, suffer mild effects

HsHs: homozygous, usually die before reproduction
Sickle cell anemia

When Malaria is present HAHs advantage: red blood
cells with abnormal hemoglobin tend to sickle when
infected by parasite and are culled out
72% HAHA; 25% HAHs; and 2.2% HsHs (die young)

Malaria not present AA advantage
99.999% HAHA; 0.001% HAHs; and 0% HsHs

With malaria, balancing selection for the heterozygote

Without malaria, directional selection for HAHA



So, how does one detect Natural
Selection in a population?
Many types of tests
The challenge is distinguishing
natural selection from signatures of
Genetic Drift
Codon Bias



In the case of amino
acids
Mutations in Position 1,
2 lead to Amino Acid
change
Mutations in Position 3
often don’t matter
(1)
Simplest Test: Ka/Ks Test
Nonsynonymous substitution rate
Synonymous substitution rate

Ka
Ks
>1

Need coding sequence (sequence that codes proteins)

Ks is used here as the “control”, proxy for neutral evolution


A greater rate of nonsynonymous substitutions (Ka) than
synonymous (Ks) is used as an indication of selection
(Ka/Ks >1)
Substitution rate: out of all the possible number of
mutations, how many fixed
(1)
Ka/Ks Test
Nonsynonymous substitution rate
Synonymous substitution rate




Ka
Ks
>1
In the absence of selection, you’d expect Ks = Ka, and for
Ka/Ks = 1
A greater rate of nonsynonymous substitutions (Ka) than
synonymous (Ks) is used as an indication of positive
selection (Ka/Ks >1)
If Ks > Ka, or Ka/Ks < 1, that would suggest purifying
selection, that selection might be preserving amino acid
composition
Summary
(1) Of the evolutionary forces that can disrupt HW Equilibrium,
Natural Selection is the only one that is adaptive
(2) Selection occurs through differential reproduction which is
NOT random
(3) Natural selection requires genetic variation upon which it can
act
(4) There are different ways in which selection can act (favoring
the extremes, or heterozygotes, or unidirectional)
Concepts
Natural Selection
Fitness
Directional,
Stabilizing,
Disruptive Selection
Balancing Selection
Selection on dominant
vs recessive alleles
The following are numbers of red, pink, and white flowers in a
population.
Generation 1:
Generation 2:
Generation 3:
(A1A1)
Red
(A1A2)
Pink
(A2A2)
White
400
600
500
200
100
0
400
300
500
1. Is the population above in Hardy-Weinberg Equilibrium?
(A) Yes
(B) No
(C) Yes in the first generation, but No in the third generation
(D) No in the first generation, but Yes in the third generation
2. What are the frequencies of alleles and
genotypes at Generation 3?
(A)A1: 0.50, A2: 0.50
A1A1: 0.25, A1A2: 0.50, A2A2: 0.25
(B)A1: 0.65, A2: 0.35
A1A1: 0.60, A1A2: 0.10, A2A2: 0.30
(C)
A1: 0.50, A2: 0.50
A1A1: 0.50, A1A2: 0, A2A2: 0.50
(D)
A1: 0.50, A2: 0.50
A1A1: 0.25, A1A2: 0, A2A2: 0.25
3. In the previous example (from question #1), what
might be going on?
(A) Genetic Drift
(B) Balancing Selection
(C) Recombination
(D) Directional Selection
(E) Disruptive Selection
4. What would Darwin say?
(A) Genetic drift is also an important evolutionary force
that occurs through random survival and reproduction
(B) Individuals pass alleles onto their offspring intact
(inheritance is particulate)
(C) Selection acts on genetic variation such as Mutations
(D) Selection acts on differential fitness of genetically
distinct offspring
(E) Evolution occurs at the level of the individual
Answers:
1B
2C
3E
4D
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