Download Genetic Variation

Genetic Variation within
Populations
Population Genetics
Darwin’s Observations
Genetic Variation
• Underlying phenotypic variation is genetic
variation.
• The potential for genetic variation in individuals
of a population is unlimited
• Unlimited genetic variation, in the form of new
alleles and new combinations of alleles, increases
the chance that a population will survive future
environmental changes.
• How do new alleles arise in a population?
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Natural Selection & Evolution
• Natural selection is differential survival and
reproduction.
• Populations (not individuals) evolve.
• Populations are defined as a group of
interbreeding individuals of a single species that
share a common geographic area.
• Evolution is measured as the change in relative
proportions of heritable variation in a population
over a succession of generations.
Population Genetics
1. Integrates Darwin’s Theory of Natural Selection
with Mendelian Genetics
2. Genes/alleles and their relative abundance
(frequency) within and among populations.
3. How/why do allele frequencies change?
4. Microevolution
5. Assessing genetic variation using molecular
techniques.
The life cycle of an imaginary population of mice
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Hardy-Weinberg Principle
If:
1) Mating is random across the entire population.
2) All genotypes (individuals) have equal success at surviving or
reproducing (no selection).
3) There is no migration/emigration of individuals (gene flow).
4) There is no mutation.
5) Population is large enough so that the allele frequencies do not
change from generation to generation just by chance alone (random
genetic drift).
Then: allele frequencies will not change from one generation to the
next and the population is said to be in Hardy-Weinberg
equillibrium
A gene pool with allele frequencies of 0.6 for allele A
and 0.4 for allele a.
Allele and genotype frequencies throughout the
life cycle in a numerical simulation
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When the adults in our model mouse population make gametes,
they produce a gene pool in which the allele frequencies
are identical to the ones we started with a generation ago
Hardy-Weinberg Calculations
• If frequency of the dominant allele (A) in
the population is p, and the frequency of the
recessive allele (a) is q, then p + q = 1
• Frequency of heterozygotes (Aa), dominant
homozygotes (AA) and recessive
homozygotes (aa) is:
•
p 2 + 2pq + q2 = 1
• AA Aa
aa
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Hardy -Weinberg
• If p+q=1.0 (allele frequencies)
• Then p2 + 2pq + q2 = 1.0 (genotype
frequencies)
• If you know the allele frequencies, you can
predict the genotype frequencies:
Selection can cause allele frequencies to change across generations
(1) Persistent selection can produce substantial changes in allele
frequencies over time
(2)Each curve shows the change in allele frequency over time
under a particular selection intensity.
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Frequencies of the AdhF allele in four populations of fruit flies over 50 generations
Red + orange dots = flies reared on food spiked with ethanol
Macrophage
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What accounts for this variation?
Random? Past epidemics
(plague, smallpox)?
What will happen to this variation
in the future? Will Δ32 allele
increase in frequency?
Selection will increase the
frequency of Δ32 allele
• Selection is relatively weak
• The favored allele is recessive
• and the favored genotype is very rare
• The change in allele frequency (response to
selection) will be relatively slow
Industrial Melanism
• Classic example of natural selection
• Kettlewell (1959) conducted experiments to
measure the survival of different genotypes
• Calculated change in frequency of dark and
light individuals
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Battling malaria: natural
selection is fast!
• DDT developed in
1942, used in India in
late 1940’s
• 10 years later, nearly
useless due to resistant
mosquito strains
• 95% effective initially
but 16 months later
only 20% effective
Mutation is a weak mechanism of evolution
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Mutation causes variation
e.g. Sickle cell anemia
• Hemoglobin gene
• DNA sequence containing a specific mutation in
the nucleotide sequence causes a hydrophilic
amino acid, glutamine, to be substituted by a
hydrophobic amino acid, valine.
• Profound effects on the folding pattern of the
hemoglobin, altering its functionality.
‘Normal’ Homozygotes
• Homozygous
individuals, AA
• Healthy
• In the A allele, the 6th
codon is CTC =
glutamine
Sickle-cell Homozygotes
• In the a allele, the 6th
codon has mutated to
CAC = valine
• causes distortion in shape
of red blood corpuscles
• 80% of homozygous (aa)
individuals die before
reproducing
• why still around?
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Effect of Migration and Small
Population size
• Gene Flow - the gradual exchange of
genes/alleles between two populations
brought about by the dispersal of gametes or
the migration of individuals.
• Genetic Drift - random variation in allele
frequency from generation to generation.
Most often observed in small populations.
Migration can alter allele and genotype frequencies
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Population size and drift
• Small populations vary more in allele
frequencies due to sampling effects from
one generation to the next
• variance in frequency of an allele with
frequency depends on population size, N
• Smaller N => more variance, more drift
Genetic Drift
• Random sampling/variation in allele frequency
from generation to generation
• Occurs when the number of reproducing
individuals in a population is too small to ensure
that all the alleles in the gene pool will be passed
to the next generation in their existing frequencies
Chance events (Genetic Drift) can alter allele and genotype frequencies
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Flip a coin
• Observe 10 sets of 20 coin tosses
• and 10 sets of 4000 coin tosses
• On average all sets would have 50% heads
and tails
• But it is more likely to flip 12 heads : 8 tails
in the small population
• than 2400 heads : 1600 tails in the large
population
Bottlenecks
• Populations may go through a bottleneck in
size
• Out of many individuals, only a few
contribute to the next generation
• A special type of bottleneck is the reduction
in population size associated with
colonization - founder effect
Genetic Bottleneck
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Small Populations & The
Founder Effect
“The establishment of a new population by a
few original founders (in an extreme case,
by a single fertilized female) that carry only
a small fraction of the total genetic variation
of the parental population.” (Mayr, 1963)
The Amish
• Small group of Germans began the Amish
community in Pennsylvania
• 1 possessed an allele for polydactylism
(more than five fingers or toes on a limb).
• After 200 years of reproductive isolation
• the number of cases among the Amish
population exceeds the number of cases
occurring in the entire world’s population
Inbreeding alters genotype frequencies
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Inbreeding
• Self-fertilization
• Sewell Wright: Inbreeding Coefficient (F)
• F quantifies the probability that the two alleles of a given
gene in an individual are identical because they are
descended from the same single copy of the allele in an
ancestor.
– If F =1 all individuals in the population are homozygous, and both
alleles in every individual are derived from the same ancestral
copy.
– If F=0 no individual has two alleles derived from a common
ancestral copy
Inbreeding
•
•
•
Sewell Wright: Inbreeding Coefficient (F)
Based on the inverse relationship between inbreeding and the
frequency of heterozygotes
As inbreeding increases, heterozygosity decreases
F= He - Ho /H e
He = expected heterozygosity
Ho = observed heterozygosity
In a completely randon mating population the expected and
Observed levels of heterozygosity will be equal so F=0
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Inbreeding Depression
• Inbred populations often have a lowered
mean fitness.
• Inbreeding depression is a measure of the
loss of fitness caused by inbreeding
• Inbreeding results in higher levels of
homozygosity
• Some recessive alleles are deleterious
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