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L22

Population
Genetics!
Hardy
Weinburg
Equilibrium, !
And Natural
Selection!

In domestic selection,
breeders and
agriculturalist determine
the fitness of individuals
by choosing them to
breed due to their
desirable characters.!

In natural populations,!
natural selection acts on traits
that are closely related to
fitness (affecting survival and
reproduction)!

3!

Selection changes the character or trait distribution of


quantitatative characters described by the mean and
variance of a phenotype distribution.!

4!

5!

While quantitative genetics provides the


means to predict changes in character
distributions and estimate the influence of
genetic and environmental effects, it does
not provide insight into mechanisms of
genetic change in populations.!

"
Classic Population Genetics predicting and explaining
changes in allele frequency in a population."
"
The study of the frequencies of different genotypes in
populations and the changes in those frequencies that result from
patterns of mating, natural selection, mutation, migration and
random chance. Griffiths et al. "
"
Study of allelic transmission and genotype variation within and
among populations, the units of microevolution.!
!

Genetic principals of inheritance and transmission and the study of


mechanisms of (population) genetic change.!
!

Study of the consequences of Mendelian inheritance at the population


level, including the mathematical description of a populations genetic
composition and how it changes over time"
6!

Punnett Square model of


population genetics with a
large pool of parental
gametes of equal frequency,
and an expected offspring
generation, !
!
assuming non-assortative
mating and a large
population!
!
!
If the offspring generation
breeds randomly and each
sex has the same allele
frequencies, then they will
have the same allele
frequencies in their gene pool
as their parents!
!

0.5!
A(p)!
!

0.5!
a(q)!
!

2!
0.25p
A(
p)!
0.5!

0.5! a(q)! 0.25pq!


or,
if

0.25pq!
!
0.25q2!

AA + Aa + aa =1
A=p
a=q
p2 + 2pq + q2 = 1

Hardy - Weinburg equilibrium


!

7!

Why is Hardy Weinburg Equilibrium (HWE) useful ?!


It is a null model - expect in the absence of interactions!
!
(1)Genotype frequencies may vary while allele frequencies do not !
(2)studying allele frequencies addresses this disconnect. !
(3)studying allele frequency reduces the number of variables.!
!
Allele frequencies may vary between:!
0 (extinct), <0.01 (mutant), >0.01 (polymorphic) and 1.0 (fixed) . !
!
Hardy-Weinburg, predict the variation you expect due to genetic
mechanisms alone (meiotic sex, or mitotic), without considering ecological
constraints."

p2 + 2pq + q2 = 1 !
count 3 genotypes if codominant, !
count the proportion of recessive phenotypes (q2) if fully dominant; !
& calculate q, p (1-q) and the expected genotype frequencies.!
Then consider "
Effects of population structure, size, migrants, predators and competitors!

Assuming random mating in a large population,there


will be an expected relationship between transmitted
gametes (the marginal frequencies define the gene pool) and
the expected genotype frequencies!
(in the offspring generation) !
p2 + 2pq + q2 = 1 !

17!

The gene pool of a diverse population can be


characterized by genotype frequencies or most
simply, allele frequencies!

Relax the assumption of equal parental allele frequency.!


!
p or q could range from 0 to 1.0!
!
p = 0 (extinct), !
!q = 1 (fixed)!
p < 1%, (mutant),
!q = majority = wild type!
p > 1%, < 99%, !
!q < 99%, > 1% (polymorphic)!
p = 1.0 (fixed), !
!q = 0 (extinct) !
!
!
15!

Eggs!

Lets say you are looking at a


wild population of peas where
the allele frequencies are not
equal

A(p = 0.7)!

Sperm!

A!
(p = 0.7)!

Predict the genotype frequency in the next generation

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(1)If A=0.6 what is the


frequency of the a allele ?

A(p = 0.7)!
A(p = 0.7)!

Eggs!

(2) other genotype


frequencies ?

Sperm!

AA!
(p2 = 0.49)!

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Eggs!

Predicting genotype
diversity in a population.

Sperm!

A(p = 0.7)!

a(q = 0.3)!

A!
(p = 0.7)!

AA!
(p2 = 0.49)!

Aa!
(pq = 0.21)!

a!
(q = 0.3)!

Aa!
(pq = 0.21)!

aa!
(q2 = 0.09)!

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Cystic Fibrosis: Affected persons are homozygous for the recessive


disease allele (F508), a syndrome that can be readily diagnosed. By
convention, recessive alleles are designated the q allele, the genotype
cf/cf".

Affected individuals = 1/ 2500!


cf/cf" genotype frequency = q2 = 1/2500 (0.0004) !
cf - the allele frequency
If q = 1/50 (0.02);

q = 1/2500 q =1/50 (0.02)!


2

p = 1-q = 49/50 or 0.98

The frequency of heterozygous carriers Cf / cf is 2pq


f (Cf / cf)

= 2pq= 2 ( 1/50 or 0.02 ) * (49/50 or 0.98)


= 1/25 or 0.039 (one copy each)
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Most mutations are found in heterozygotes at low


homozygote frequencies in Hardy Weinburg
Equilibrium populations.

p2

q2

+ 2pq +
=
Weinburg
1Hardy
!
Generalizations

In specifically a population
with genotypes in HW
equilibrium:!
!
(1) If there are equal allele
frequencies (0.5), then
heterozygotes are in the
highest frequency.!
(2) At unequal frequencies, a
high proportion of low
frequency alleles alleles are
in heterozygotes. For fully
dominant allele interactions,
recessives in heterozygotes
are hidden, carried, masked
or are not a direct target of
selection.

Hardy Weinburg Equilibrium!


a null model!
Assuming:"
No selection on heritable phenotype
differences!
Random mating!
Large population!
No mutations!
No significant migration (emigration or
immigration). !
!

For Natural Selection to occur: (see J.Endler, Natural


Selection in the Wild. Princeton)
(1)There must be phenotypic variation, natural selection acts
on phenotype variation and indirectly on genetic
variation.
(2) Phenotypic variation under selection must have a
consistent relationship with fitness differences
(survivorship, fecundity, mating behaviour etc).
(3)Selection on phenotypic differences has to have a genetic
effect that is at least partially independent of
environmental effects.
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Selection
survivorship
fecundity!
Zygotes -> natural selection -> adults reproducing!
!
!
Assumptions!

Fitness differences are (1,2) due to variation in survivorship -life


history phenotype!
Survival differences are (3) due to allelic substitutions at 1 locus!
Fitness differences are constant through all life stages and do not
change with frequency!
!
No mutation, drift, or migration.!
Equal genotype fecundity- differences are unimportant!
!
18!


The population is initially in Hardy-Weinburg equilibrium.
In this population the allele frequencies are 0.5 (A1) : 0.5(A2), thus:

q2= 0.25,

p2 =0.25 and

2pq = 0.5

If there are 100 individuals in a diploid population, there are 200


copies of the gene, in this case, of 2 allelic types A1 and A2.

Homozygotes have 2 copies of each allele. For example, A2A2
individuals contribute 2* (0.25*100)= 50 A2 alleles to the gene pool.

Heterozygotes have 1 copy of each allele. Thus heterozygotes
contribute 1* (0.5* 100) = 50A2 alleles to the gene pool.

The total A2 alleles before selection = 100/200 = 0.5A2= q.

Similarly, there are 100 A1 alleles distributed over 2 genotypes.



The gene pool is the sum of the alleles in gene A (A1 + A2)= 1.0,
providing the gene frequencies for the next generation.

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Frequency

0.5!

Parental generation
at conception.

0.25!

0.25!

100 individuals!

Phenotypic value
Genotype
Zygote frequency

A1A1
p2

A1A2
2pq

A2A2
q2

Directional Selection on a fully dominant allele: Assume A2 allele is


dominant lethal.
w A1 A1 = 1, w A2 A1 = 0
w A2A2 = 0

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Frequency

0.5!

Genotype
Zygote frequency
Relative fitness
Product

0.25!

Parental generation
at conception.
0.25!

Phenotypic value
A1A1
A1A2
p2
w11
p2w11
(0.25*1.0)

2pq
w12
2pqw12
(0.5*0)

A2A2
q2

w22
q2w22
(0.25 *0) !

Directional Selection on a fully dominant allele: Assume A2 allele is


dominant lethal.
w A1 A1 = 1, w A2 A1 = 0
w A2A2 = 0

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0.5!

Frequency

22
0.25!

w =

Adult frequency

0.25!

Phenotypic value
A1A1
A1A2

Genotype
Zygote frequency
Relative fitness
Product

Parental generation
at conception.

p2
w11
p2w11
(0.25*1.0)
p2w11 / w

2pq
w12
2pqw12
(0.5*0)
2pqw12/ w

A2A2
q2

w22
q2w22
(0.25 *0) !
q2w22 / w

0.25 / 0.25 = 1.0, 100 % A1 homozygotes!

Directional
Selection on a fully dominant allele: Assume A2 allele is

dominant lethal.
wA1 A1 = 1, wA2 A1 = 0
wA2A2 = 0

Selection (2) !
Directional or elimination selection on a fully recessive allele in a
gene with 2 alleles A1 , A2, HWE , 100 individuals, p & q = 0.5"
Assume A2A2 fitness is 0, A1 is fully dominant over A2.

A1 = 0.5, A2= 0.5

w A1 A1 = 1,

Genotype
Zygote frequency
Relative fitness
w=
Product
Adult frequency

A1A1

w A2 A1 =1

w A2A2 = 0

A1A2

A2A2

p2 = 0.25 2pq = 0.5


w11 = 1.0
w12 = 1.0
p2w11 =0.25
2pqw12 = 0.5
p2w11 / w
2pqw12 / w

q2 = 0.25
w22 = 0
q2w22 = 0
q2w22 / w

= (0.25*1.0)/0.75 = (0.5*1.0)/0.75!

75 adults left

0.33A1A1 (25) ,

0.66 A1A2 (50)!

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The frequency of A2 after selection (q1) is a function of allele


frequencies before selection, and the relative fitness of
genotypes that carry that allele.!
2
"
%
1 2 p0q0 w12 q0 w 22
q1 = $
'+
&
2#
w
w

p0q0 w12 + q02 w 22


=
w

1 " 0.5 %
0
q1 = $
= 0.33
'+
2 # 0.75 & 0.75

Count alleles in the remaining individuals after selection (75)


50A2 / [50(A2heterozygote)+50(A1heterozygote)+50(A1 homozygote)]

A2 =50/150 =0.33A2 allele frequency in the gene pool.


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Directional selection on a fully recessive allele - Next Generation ?

The allele frequency of the embryonic A2 allele was 0.5!


But, after selection: f(A2) =0.33A2 allele frequency in the gene pool.

The breeding population


after selection
Directional selection
favors one allele over
another, but recessive
alleles are protected
from selection in the
heterozygote. The
selected parents (favored
or disfavored) produce
gametes and they go into
a pool of random mating
(gene pool).

GENE
POOL

f(A1) = 0.66
(p)

f(A2)= 0.33
(q)

f(A1) = 0.66
(p)

0.44
f (A12) = p2

0.22
f(A1A2)= pq

f(A2)= 0.33
(q)

0.22
f(A1A2) = pq

0.11
f(A22) = q2

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Sexual Selection is a kind of


selection, where the
environment is social,
competition is for mates,
selection is generally stronger
on males and reproductive
fitness may eventually have
other costs that oppose
natural selection.!

Fitness (w) is the ability of different individuals, phenotypes


and /or genotypes to survive and reproduce.
Relative
Fitness measures the proportional contribution
of each reproductive parental genotype to the pool of
gametes in each generation.
Fitness may be:
or

frequency dependent
frequency independent.

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Darwinian Selection



(1)Variation

(2)Heredity

(3)Natural Selection

Frequency dependence
Nature 441:633-636

Darwin 200: Nature vol 457 pp 790


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Polymorphic classes that have Classical Mendelian


inheritance patterns , classify as alleles (A,a)

10

Visible phenotypes (morphology, behaviour, physiology)


Chromosome variation and haplotypes
Restriction site variation
Immunologic polymorphism
Amino acid sequence polymorphism
DNA base pair variation (SNPs)
Satellite DNA

Polymorphism is phenotype variation related to allelic or chromosome


variation.
In population genetics, polymorphism refers to phenotypes with
frequencies > 1% in the population. The predominant phenotype or
genotype is the wild type. Rare phenotypes are called mutants (<
1%).

Postman (below) and rayed phenotype!

Variation in
color and
allele
pattern!

6!

Variation in
chromosome
inversions!

7!

Detecting
variation in
microsatellites"

Protein phenotype implying


homozygotes and heterozygotes
visualized on electrophoretic gels

8!

Asterisks mark
restriction haplotype
variation among 58
D. pseudoobscura!
chromosomes !
F0, 1 can be used to
estimate allele
frequencies!

9!

Variation among homologous


DNA sequences!