Population Genetics

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Population Genetics
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
3
1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
How does evolution work at a genetic level?
Population Genetics and the Modern Synthesis
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
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1859 Darwin and the birth of modern
biology (explaining why living things are as they
are) Heritable Traits and Environment ?
Evolution
Review
Mendel Heredity works by the transmission of
particles (genes) that influence the expression
of traits
How does evolution work at a genetic level?
Population Genetics and the Modern Synthesis
Avery, McCarty, and MacLeod Genes are DNA
Watson and Crick Heres the structure of DNA
How can we describe the patterns of evolutionary
change through DNA analyses? Evolutionary Genetics
Modern Genetics Heres how DNA influences the
expression of traits from molecule to phenotype
throughout development
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The Darwinian Naturalists
The Modern Synthesis
The Mutationists
Ernst Mayr
Selection is the only mechanism that can explain
adaptations mutations are random and cannot
explain the non-random fit of organisms to
their environment
T. H. Morgan
R. Goldschmidt
The discontinuous variation between species can
only be explained by the discontinuous variation
we see expressed as a function of new mutations
the probabilistic nature of selection is too weak
to cause the evolutionary change we see in the
fossil record
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Sewall Wright Random chance was an important
source of change in small populations
The Modern Synthesis
J. B. S. Haldane Developed mathematical models
of population genetics with Fisher and Wright
R. A. Fisher
Multiple genes can produce continuous variation,
and selection can act on this variation and cause
change in a population
Theodosius Dobzhansky Described genetic
differences between natural populations
described evolution as a change in allele
frequencies.
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Population Genetics I. Basic Principles
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Population Genetics I. Basic Principles
A. Definitions - Population a group of
interbreeding organisms that share a common gene
pool spatiotemporally and genetically defined
- Gene Pool sum total of alleles held by
individuals in a population - Gene/Allele
Frequency of genes at a locus of a particular
allele - Gene Array of all alleles at a
locus must sum to 1. - Genotypic Frequency
of individuals with a particular genotype -
Genotypic Array of all genotypes for loci
considered 1.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)



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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1


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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1
''A' alleles 120 80 0 200/400 0.5

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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array
AA Aa aa
Individuals 60 80 60 (200)
Genotypic Array 60/200 0.30 80/200 .40 60/200 0.30 1
''A' alleles 120 80 0 200/400 0.5
'a' alleles 0 80 120 200/400 0.5
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations 1.
Determining the Gene and Genotypic Array 2.
Short Cut Method - Determining the Gene Array
from the Genotypic Array a. f(A) f(AA)
f(Aa)/2 .30 .4/2 .30 .2 .50 b.
f(a) f(aa) f(Aa)/2 .30 .4/2 .30 .2
.50 KEY The Gene Array CAN ALWAYS be computed
from the genotypic array the process just counts
alleles instead of genotypes. No assumptions are
made when you do this.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 1. If a population
acts in a completely probabilistic manner,
then - we could calculate genotypic arrays
from gene arrays - the gene and genotypic
arrays would equilibrate in one
generation
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 1. If a population
acts in a completely probabilistic manner,
then - we could calculate genotypic arrays
from gene arrays - the gene and genotypic
arrays would equilibrate in one generation 2.
But for a population to do this, then the
following assumptions must be met (Collectively
called Panmixia total mixing) -
Infinitely large (no deviation due to sampling
error) - Random mating (to meet the basic
tenet of random mixing) - No selection,
migration, or mutation (gene frequencies must not
change)
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium Sources of
Variation Agents of Change Mutation N.S. Re
combination Drift - crossing
over Migration - independent
assortment Mutation Non-random Mating
VARIATION
So, if NO AGENTS are acting on a population, then
it will be in equilibrium and WON'T change.
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium 3. PROOF - Given a
population with p q 1. - If mating is
random, then the AA, Aa and aa zygotes will be
formed at p2 2pq q2 - They will grow up and
contribute genes to the next generation - All
of the gametes produced by AA individuals will be
A, and they will be produced at a frequency of p2
- 1/2 of the gametes of Aa will be A, and thus
this would be 1/2 (2pq) pq - So, the frequency
of A gametes in the gametes will be p2 pq p(p
q) p(1) p - Likewise for the 'a' allele
(remains at frequency of q). - Not matter what
the gene frequencies, if panmixia occurs than the
population will reach an equilibrium after one
generation of random mating...and will NOT change
(no evolution)
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq.
Genotypes, F1
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's f(A) p .36 .48/2 0.6 f(A) p .36 .48/2 0.6 f(a) q .16 .48/2 0.4 f(a) q .16 .48/2 0.4
Genotypes, F2
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium
AA Aa aa
Initial genotypic freq. 0.4 0.4 0.2 1.0
Gene freq. f(A) p .4 .4/2 0.6 f(A) p .4 .4/2 0.6 f(a) q .2 .4/2 0.4 f(a) q .2 .4/2 0.4
Genotypes, F1 p2 .36 2pq .48 q2 .16 1.00
Gene Freq's f(A) p .36 .48/2 0.6 f(A) p .36 .48/2 0.6 f(a) q .16 .48/2 0.4 f(a) q .16 .48/2 0.4
Genotypes, F2 .36 .48 .16 1.00
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility 1. If
no real populations can explicitly meet these
assumptions, how can the model be useful?
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Population Genetics I. Basic Principles A.
Definitions B. Basic computations C.
Hardy-Weinberg Equilibrium D. Utility 1. If
no real populations can explicitly meet these
assumptions, how can the model be useful? It is
useful for creating an expected model that real
populations can be compared against to see which
assumption is most likely being violated.
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Example CCR5 a binding protein on the surface
of white blood cells, involved in the immune
response. CCR5-1 functional allele CCR5 D32
mutant allele 32 base deletion Curiously,
homozygotes for D32 are resistant to HIV, and
heterozygotes show slower progression to AIDS.
Mutant allele interrupts viruss ability to
infect cells.
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Example CCR5 a binding protein on the surface
of white blood cells, involved in the immune
response. CCR5-1 functional allele CCR5 D32
mutant allele 32 base deletion Curiously,
homozygotes for D32 are resistant to HIV, and
heterozygotes show slower progression to AIDS.
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GENOTYPES
32 base-pair deletion, shortening one of the
fragments digested with a restriction enzyme
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GENOTYPE OBSERVED EXPECTED O - E (O E)2 (O E)2/E
1/1 223 224.2 -1.2 1.44 0.006
32/1 57 55.4 1.6 2.56 0.046
32/32 3 3.4 -0.4 0.16 0.047
283 X2 0.099
1/1 223/283 0.788 p 0.788 0.201/2
0.89 32/1 57/283 0.201 32/32 3/283
0.011 q 0.011 0.201/2 0.11 Expected 1/1
p2 x 283 (0.792) x 283 224.2 Expected 1/32
2pq x 283 (0.196) x 283 55.4 Expected 32/32
q2 x 283 (0.0121) x 283 3.4
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So this population is in HWE at this locus. HIV
is still rare, and is exerting too small a
selective pressure on the whole population to
change gene frequencies significantly.
This is the percentage of CCR5 delta 32 in
different ethnic populations European Descent
16 African Americans 2 Ashkenazi Jews 13
Middle Eastern 2-6
Why does the frequency differ in different
populations? Drift or Selection?
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Allelic frequency of CCR5-d32 in Europe
Galvani, Alison P. , and John Novembre. 2005. The
evolutionary history of the CCR5-D32
HIV-resistance mutation. Microbes and Infection 7
(2005) 302309
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Why Europe? - the allele is a new mutation -
was it selected for in the past?
Spread of the Bubonic Plague
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Why Europe? - the allele is a new mutation -
was it selected for in the past?
Smallpox and CCR5
Smallpox in Europe
In the 18th century in Europe, 400,000 people
died annually of smallpox, and one third of the
survivors went blind (4). The symptoms of
smallpox, or the speckled monster as it was
known in 18th-century England, appeared suddenly
and the sequelae were devastating. The
case-fatality rate varied from 20 to 60 and
left most survivors with disfiguring scars. The
case-fatality rate in infants was even higher,
approaching 80 in London and 98 in Berlin
during the late 1800s. Reidel (2005). The WHO
certified that smallpox was eradicated in 1979
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Relationships Between Smallpox and HIV
1. Smallpox, on the other hand, was a
continuous presence in Europe for 2,000 years,
and almost everyone was exposed by direct
person-to-person contact. Most people were
infected before the age of 10, with the disease's
30 percent mortality rate killing off a large
part of the population before reproductive age.
ScienceDaily (Nov. 20, 2003) 2. The HIV
epidemic in Africa began as vaccination against
smallpox waned in the 1950s 1970s. Perhaps
vaccinations for smallpox were working against
HIV, too. 3. In vitro studies of wbcs from
vaccinated people had a 5x reduction in infection
rate of HIV compared to unvaccinated controls.
Weinstein et al. 2010
So, it may have been selected for in Europe, and
now confer some resistance to HIV.