POPULATION GENETICS

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POPULATION GENETICS
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Annotated sequence of human chromosome 1
symbolizes the breakthrough of the year 2007
the realization that DNA differs from person to
person much more than researchers had suspected.
This conceptual advance could transform medicine
but also threaten personal privacy
Its all about me
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WHAT IS A POPULATION?
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• WHAT IS A POPULATION?
• A species is distributed over a wide range of
  habitats
• A population is a local group within a species.

Concept of a population implies that there is not
completely free interbreeding between populations
but that there is some restriction of
interbreeding. This allows populations to
undergo some evolution as a unit and to develop
local adaptations.
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THERE IS VARIATION WITHIN AND BETWEEN POPULATIONS
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Key Concepts Differences exist between
populations

• Variation between populations reflects the
  product of local adaptation or geographical
  isolation

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Variation within populations

• In populations, genetic variability exists in
  genes, proteins and chromosomes.
• Variation within populations can be identified by
  experimental techniques

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Key Concepts Population Variation
Homozygotes for the Esterase-5 locus in D.
pseudoobscura
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Natural variants for hemoglobin A in humans
Homozygotes for variant allele
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Variation in Homo sapiens (low compared to other
species) 85 of total variability is found in
local populations. 6 of total variability is
found among local populations within geographical
races 9 is found among geographical races
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HIDDEN GENETIC VARIATION Substantial genetic
variation may underlie characters that show no
morphological variation. Sometimes this
variation is revealed under different selection
pressures.
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HIDDEN GENETIC VARIATION The number of scutellar
bristles is held at 4 during development.
In the presence of another gene, the recessive
scute mutation, bristle number varies and can
be selected for. Lines with 0 or 1 bristles
and 3-4 bristles can be obtained. If scute is
removed, these lines now have 2 and 6 bristles
respectively and the trait is inherited. Thus
hidden genetic variation can be revealed under
selective pressures
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• Sources of variation
• Mutation
• Recombination
• Reassortment (phenotypic)

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THE POPULATION AS A UNIT OF EVOLUTION
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POPULATIONS ARE WHERE EVOLUTION OCCURS!!
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• Darwin and Wallace observed that natural
  populations tend to remain stable in spite of
  unlimited capacity to enlarge.
• Other factors must limit the size of a population
• There must be a competition for those resources
  (food, space)

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• Led to the concept of selective survival which
  Darwin called Natural Selection
• The individual is the unit of selection
• To study the role of evolution, it became
  necessary to determine the frequencies of various
  genotypes in the population and what was
  happening to those genotypes

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Goal of Population Genetics To understand the
genetic composition of populations and the
forces that determine and change that composition
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Summary of evolutionary equilibrium between
mutation and selection

• New alleles arise in populations by mutation
• When allele has affect on fitness, selection will
  drive frequency towards an equilibrium with
  wild-type allele
• Equilibrium value is determined by relative
  selection coefficients for heterozygous and
  homozygous individuals for new allele
• If new allele has no effect on fitness, genetic
  drift will determine its frequency

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GENE POOLS
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IA
IA
HbS
adh1
adh2
adh2
HbS
adh1
IB
IB
i
i
HbA
HbA
i
What is a gene pool? The sum of all available
genetic variation in a population
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IA
IA
HbS
adh1
adh1
HbS
adh2
IB
IB
i
i
HbA
HbA
i
Selection acts to remove alleles from a gene
pool
adh2
adh2
adh2
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HARDY-WEINBERG LAW
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Hardy Weinberg law

• Hardy Weinberg Law
• The frequency of alleles in a population reaches
  equilibrium in one generation and stays at
  genetic equilibrium generation after generation.

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Hardy Weinberg law

• This law is a simplification of complex events.
  There are certain assumptions that must be
  present for the law to apply
• The population is infinitely large. (Since this
  is impossible, large populations are studied when
  possible because they are mathematically similar
  to infinite ones.)
• Mating is random with regard to the trait(s)
  under study.
• There is no natural selection of the trait(s)
  under study.
• No mutation occurs.
• No migration occurs.

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THE RELATIONSHIP BETWEEN ALLELE FREQUENCIES AND
PHENOTYPE FREQUENCIES WHEN THERE IS NO EVOLUTION
(HARDY-WEINBERG LAW HOLDS)
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EXAMPLES FOR AUTOSOMAL GENES
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To evaluate gene frequencies in populations, two
pieces of information are needed 1. What is the
frequency of alleles in the population? 2. What
are the genotype frequencies? The relationship
between allele frequency and genotype frequency
can be modeled using probability and the binomial
expansion.
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P the frequency of allele 1 in the
population Q the frequency of allele 2 in the
population P Q 1 (P Q)N the frequency of
genotypes in a population where Nthe number of
alleles any genotype can have 2 P2
individuals that are homozygous for allele 1 Q2
individuals that are homozygous for allele 2 2PQ
individuals that are heterozygous
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Example using MN blood types
Within a population, there are MM 12
individuals MN 53 individuals NN 12
individuals Total individuals 77 Total number
of alleles154
P (freq of M allele) M alleles/total alleles
(12 12 53)/154 0.5 50 Q (freq of N
allele) N alleles/total alleles (53 12
12)/154 0.5 Frequency of M N 1
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MN Blood Types using frequencies instead of
counting alleles
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MN blood group from Eskimo populations MM
0.835 MN 0.156 NN 0.009 Total 1.00 or
100 P freq of M 0.835 (1/2) 0.156
0.913 Q freq of N 0.009 (1/2)(0.156)
0.087 PQ1 Assuming Hardy Weinberg Equilibrium,
what is the frequency of the MN blood types in
the next generation? P2 (.913) ( .913)
.834 2PQ 2 (.913)(.087) .159 Q2
(.087)(.087) .0008
any evolution????
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A population of the endangered Tennessee cone
flower consists of 15 individuals. There are two
alleles in the population for the enzyme, alcohol
dehydrogenase. adh1 and adh2 10 adh1 adh1
homozygotes 1 adh1 adh2 heterozygote 4 adh2 adh2
homozygotes What is the frequency of allele
adh1? a. 10 b. 20 c. 30 d. 70 e. 90
adh1 20 1 21 Total 30 alleles 21/30
.70 70
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• Genes showing true dominance
• Cystic Fibrosis affects approximately 1 in 2000
  individuals of European descent. (For ease of
  calculation, say 2025). Assuming the population
  is in HW equilibrium, what as the frequency of
  the gene in the population?
• q2 1/2025 .0005
• q 1/45 .022
• p q 1
• p 44/45 .9777
• p2 (44/45)2 .956
• 2pq 2 (44/45) ( 1/45) .043

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SEX-LINKED GENES
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Sex Linked Genes

• In species where sex is chromosomally determined,
  humans or Drosophila for example, females have
  two X chromosomes while males have only one. In
  females, Hardy-Weinberg frequencies are the same
  as for any other locus. In males, frequencies of
  the genotypes are the same as frequencies of the
  alleles in the population.
• Males p q
• Females p2 2pq q2
• Color blindness in females is 1/1250 .0008
• q2 .0008
• q .0282 2.82 or 1/34

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Hemophilia is a sex-linked, genetic bleeding
disorder characterized by a deficiency or absence
of one of the clotting proteins in plasma. The
result is delayed clotting in an affected
individual. While deficiencies can occur in any
of the clotting proteins, factor VIII deficiency
(Hemophilia A) and factor IX deficiency
(Hemophilia B) are the most common. The frequency
of factor VIII deficiency is thought to be
approximately 1 per 10,000 male births for
factor IX deficiency, the frequency is
approximately 1 per 30,000 male births. What is
the frequency of women with hemophilia for factor
VIII? What proportion of women are carriers?
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Hemophilia is a sex-linked, genetic bleeding
disorder characterized by a deficiency or absence
of one of the clotting proteins in plasma. The
result is delayed clotting in an affected
individual. While deficiencies can occur in any
of the clotting proteins, factor VIII deficiency
(Hemophilia A) and factor IX deficiency
(Hemophilia B) are the most common. The frequency
of factor VIII deficiency is thought to be
approximately 1 per 10,000 male births for
factor IX deficiency, the frequency is
approximately 1 per 30,000 male births. What is
the frequency of women with hemophilia for factor
VIII? What proportion of women are carriers?
q 1/10,000 .0001 men with hemophilia p 1 -
.0001 .9999 Women are p2 2pq q2 1 Women
with hemophilia are q2 (.0001)2 1 X 10-8
(.00000001) Women who are carriers 2pq
2(.0001)(.9999) .0002 or .02
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EXTENSIONS TO MORE THAN TWO ALLELES
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Geographic variation in frequencies of three
alleles of the locus coding for the enzyme
leucine amino peptidase (LAP) in the blue mussel

• (p q r)2 p2(AA) 2pq(AB) q2(BB)
  2pr(AC) 2qr(BC) r2(CC) 1

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TESTING FOR HARDY-WEINBERG AGREEMENT
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• When Hardy Weinberg expected frequencies are not
  met, that tells us something about population
  dynamics. For example -
• The population is small and subject to drift and
  inbreeding
• Selection is acting on the population
• There is assortative mating
• There is significant immigration or emigration

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• Data from real populations rarely match
  Hardy-Weinberg proportions. Use a chi-square test
  to check whether deviation is larger than
  expected by chance.
• If the deviation is larger than expected,
  researchers begin to study which of the
  Hardy-Weinberg assumptions is being violated. -

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Assume that we calculate the frequency of M and N
in a population as 0.5 each from observed
distributions. There are 77 individuals in a
population. MM 12 individuals MN 53
individuals p (12 12 53)/154
0.5 EXPECTED NUMBER OF INDIVIDUALS MM
(0.25)(77) 19.25 MN (0.5)(77) 38.5 NN
(0.25)(77) 19.25 Use a chi-square test to
determine whether or not the observed data match
the expected. O E (O-E) (O-E)2 (O-E)2/E
MM 12 19.25 -7.25 52.56 2.73 MN 53 38.5
14.5 210.25 5.46 NN 12 19.25
-7.25 52.56 2.73 x2 10.92 Degrees of
freedom 3 classes - 1 (parameters estimated
from the data) - 1 1 P-value is less than 0.05
therefore we REJECT our null hypothesis. This
population is NOT in Hardy-Weinberg equilibrium!
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A population of the endangered Tennessee cone
flower consists of 15 individuals. There are two
alleles in the population for the enzyme, alcohol
dehydrogenase. adh1 and adh2 10 adh1 adh1
homozygotes 1 adh1 adh2 heterozygote 4 adh2 adh2
homozygotes The frequency of adh1 is .70 The
frequency of adh2 is .30. Is the population in
Hardy-Weinberg equilibrium? a. yes b.
no Expected under Hardy Weinberg
Equilibrium q.30, p.70 P2 .49 X 15
individuals 7.3 individuals 2pq 2(.3)(.7)
.42 X 15 6.3 individuals Q2 .09 X 15
individuals 1.35 individuals
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CONDITIONS UNDER WHICH POPULATIONS EVOLVE
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Conditions under which populations evolve

• Hardy Weinberg equilibrium describes an ideal
  condition
• Many genes can be shown to be in Hardy Weinberg
  equilibrium
• Other genes are not in Hardy Weinberg equilibrium
  and the population may be evolving for those
  traits

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Conditions under which populations evolve

• Factors that violate HW assumptions and cause
  gene frequency changes in populations
• Migration (individuals move between populations)
• Selection (to be effective in evolution,
  selection must affect reproduction)
• Small Population Size

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MIGRATION
CONDITIONS UNDER WHICH POPULATIONS EVOLVE
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Theoretical model illustrating the effect of
migration on the gene pool of a population
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Frequency of B blood type
ABO blood types in Europe reflects the Mongol
invasions of Europe
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In the body of an accounting professor, a little
bit of the Mongol hordes.
In a survey of Asian men, geneticists noticed a
distinct Y chromosome in populations from
Mongolia to Central Asia. The chromosome was
widespread and geneticists concluded that it had
become widespread because of the vigor with which
Genghis Kahn and his sons labored in their harems
(a fact noted by historians) Meanwhile, Dr
Robinson was researching his family tree and got
genotyped to help trace his roots. In searching
genetic databases, the geneticists noticed that
his X-chromosome was the same as that from
Mongolia. Genghis Kahn died in 1227 (30
generations ago). Since that time his genes have
been diluted but the Y chromosome has passed
unchanged
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SELECTION
CONDITIONS UNDER WHICH POPULATIONS EVOLVE
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Conditions under which populations evolve -
selection

• Selection (to be effective in evolution,
  selection must affect reproduction)

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Anglo-Saxons ruled England in the 5th century for
600 years 72 of modern Britons have the
Anglo-Saxon Y chromosome. Not in proportion to
the number of Britons vs. Anglo-Saxons Using
simulations, researchers calculated the
reproductive advantage if A-S were only 5 of the
population, with a reproductive advantage of
1.41 and an intermarriage rate of 7, their Y
chromosomes would reach 50 in 15
generations. Study consistent with elite status
of A-S noted by historians and shows that culture
has a real effect on genetic history
2006
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• Selection (to be effective in evolution,
  selection must affect reproduction)
• Stabilizing selection (Sickle cell anemia and
  malaria)
• Directional selection (moth example)
• Disruptive selection (against middle)

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Conditions under which populations evolve -
selection

• DIRECTIONAL SELECTION

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Evolution of drug resistance in bacteria
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1982-86 CDC Survey

• 9 of TB strains isolated from untreated patients
  and 25 of strains isolated from previously
  treated patients were antibiotic resistant

• Patient noncompliance with drug treatments is a
  major factor in evolution of antibiotic
  resistance

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1982-86 CDC Survey 9 of TB strains isolated from
untreated patients and 25 of strains isolated
from previously treated patients were antibiotic
resistant
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Factors contributing to rapid evolution of
resistance in bacterial pathogens

• Short generation times and rapid rate of
  reproduction
• Evolution proceeds quickly relative to human life
  span
• Large population densities
• Ensure resistance mutations will appear in
  population
• Strong selection imposed by antibiotics
• Increases rate of evolution in each generation
  unless bacterial population is entirely
  eliminated
• Variety of ways bacteria acquire genes speeds
  evolution
• Plasmids which carry resistance genes multiply
  rapidly
• Plasmids and genes are readily exchanged among
  bacterial populations and among different species
  through transformation, conjugation, and
  transduction

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Conditions under which populations evolve -
selection

• STABILIZING SELECTION

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The distribution of malaria caused by the
parasite Plasmodium falciparum coincides with
distribution of the Hb-S allele for sickle-cell
anemia Stabilizing Selection
The gene for sickle-cell anemia which protects
against malaria most likely evolved 3,200 7,700
after humans cleared forests and encountered
malaria-carrying mosquitoes which breed in pools.
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Conditions under which populations evolve -
selection
Sickle Cell Anemia HbA HbA dies from
malaria HbS HbA resistant to malaria, sickling
trait low HbS HbS dies from sickle cell disease
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EFFECTS OF SMALL POPULATION SIZE
CONDITIONS UNDER WHICH POPULATIONS EVOLVE
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Conditions under which populations evolve

• When populations are small, gene frequencies can
  change drastically due to chance events
• Random Genetic drift creates fixed alleles and
  loss of variability
• Inbreeding depression due to homozygosity

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Drift
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Random Genetic drift Results from random events
in small populations.
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Results of Buris study of genetic drift in 107
populations of Drosophila melanogaster show what
happens in small populations over time
Many populations have become fixed for one allele
or the other by generation 19
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Inbreeding(non-random mating)
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Nonrandom mating

• One assumption of Hardy Weinberg equilibrium is
  that mating is random in a large population
• Assumptions are violated for small populations
  because there is non-random mating

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Nonrandom mating

• Inbreeding results in a loss of heterozygosity.
  Increases the probability that an individual will
  be homozygous at many loci.
• Can be tested by using Chi Square. If observed
  heterozygotes are less than expected, inbreeding
  is probable

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Nonrandom mating

• Suppose that a population of self-fertilizing
  plants was founded by several individuals, each
  of which had the genotype Aa. In the absence
  of any other evolutionary forces, what is the
  expected number of years before 90 of the
  individuals are homozygous (AA or aa)? Assume one
  generation can be achieved per year.

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Theoretical change in homozygosity in inbreeding
populations.
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Nonrandom mating

• Heterozygosity in a population is measured by the
  inbreeding coefficient
• F (Ho -H) /Ho
• Ho original heterozygosity before inbreeding or
  expected heterozygosity under Hardy Weinberg
  Equilibrium
• H observed heterozygosity after inbreeding
• F 0 Population is in Hardy Weinberg
  equilibrium
• F 1 Complete inbreeding. There are no
  heterozygotes

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Nonrandom mating

• Consequences of inbreeding
• a. Inbreeding depression
• b. Appearance of harmful recessive traits
• c. facial and body asymmetry

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Inbreeding depression in endangered species The
Florida Panther only 30-50 cats remain.
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Nonrandom mating

• 80 of males show reduced sperm count, 93
  abnormal sperm and cryptorchidism (failure of
  testicles to descend). In order to save the
  Panther, wildlife biologists are outcrossing with
  the Texas Panther in order to restore genetic
  diversity.

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Genetic Bottlenecks
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Conditions under which populations evolve

• When inbreeding and/or drift reduces the number
  of alleles in a population, the alleles are lost.
  Mutation can bring alleles back into a
  population or create new alleles but the process
  is very slow.
• When populations rebound from near extinction,
  heterozygosity does not recover.

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In 1997, Tanksley and McCouch (Science
2771063-1066) wrote about the domestication and
breeding of crop plants (specifically, tomato and
rice). The following figure has been modified
from this article. The circles represent all the
different alleles that exist in each of the
populations (wild plants, early domesticates, and
modern varieties)
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Conditions under which populations evolve

• Genetic bottlenecks and founder effects
• The cheetah is unusual among felids in exhibiting
  near genetic uniformity at a variety of loci
  previously screened to measure population genetic
  diversity.
• It has been hypothesized that a demographic crash
  or population bottle-neck in the recent history
  of the species is causal.

• The timing of a bottleneck is difficult to
  assess, but certain aspects of the cheetah's
  natural history suggest it may have occurred near
  the end of the last ice age (late Pleistocene,
  approximately 10,000 years ago)
• Proc. Natl. Acad. Sci. USA. 1993 April 15 90
  (8) 31723176

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Nonrandom mating

• Non-random mating in large populations
• 1. Assortative mating Positive assortative
  mating in humans for skin color, height, ethnic
  subgroup
• 2. Does random mating occur for genes vs people?
  Some genes are in HW equilibrium (ABO, HLA, MN
  blood groups )
• 3. When assortative mating occurs, there is a
  deficiency of heterozygotes.

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THE ROLE OF GENETICS IN CONSERVATION BIOLOGY
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Conservation Biology

• Human activities are reducing the available
  habitat and altering the environment for many
  species, resulting in declining numbers and
  escalating rates of extinction.
• Intelligent conservation efforts must consider
  survival of gene pools, as well as survival of
  individuals.

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Conservation Biology

• Population viability analysis is used to
  determine how large a population needs to be to
  prevent extinction within a set period of time.
  An adequate gene pool is needed to ensure the
  potential for the population to evolve over time.
  
• Inbreeding has occurred in zoos and game
  management programs, and is now a recognized
  concern in developing conservation strategies.

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• END