Download Basic Premises of Population Genetics

Population genetics is concerned with
the origin, amount and distribution of
genetic variation present in populations of
organisms, and the fate of this variation
through space and time.
The fate of genetic variation through
space and time defines evolution within a
species, so population genetics also
provides the basis for microevolution
Basic Premises of Population Genetics



DNA can replicate
DNA can mutate and recombine
DNA encodes information that interacts
with the environment to influence
phenotype
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DNA Can Replicate
Because of replication, a
single type of gene can exist
both in time and space in a
manner that transcends the
individuals that temporarily
bear the gene.
Identity by Descent
Some alleles are identical because they
are replicated descendants of a single
ancestral allele
2
The Existence of Genes in Space and Time


Is manifest only at the level of a
reproducing population
Provides the spatial and temporal
continuity that is necessary for
evolution
Deme
A Deme is a local population of
reproducing individuals that has
physical continuity over time and
space. Demes are the lowest
biological level that can evolve.
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Demes are Characterized by Genotype Frequencies.
E.g., Consider a Population of Pueblo Indians Scored
for the MN Blood Group Type
Blood
Type
M
Genotype
MM
MN
NN
Number
83
46
11
140
Genotype
Freq.
83/140=
0.59
46/140=
0.33
11/140=
0.08
1
MN
N
Total
Demes are Characterized by Genotype Frequencies.
E.g., Consider a Population of Australian Aborigines
Scored for the MN Blood Group Type
Blood
Type
M
Genotype
MM
MN
NN
Number
9
113
250
Genotype
Freq.
9/372 =
0.024
MN
N
Total
113/ 372 250/ 372
= 0.304 = 0.672
372
1
4
Demes with the Same Alleles Can Have
Very Different Genotype Frequencies:
Pueblo Indians
MM
0.59
MM
0.024
MN
0.33
NN
.08
Australian Aborigines
MN
0.304
NN
0.672
Gene Pool
A Gene Pool is the population of
gene copies that are collectively
shared by the individuals of a
deme.
5
Gene Pools are Characterized by Gamete Frequencies (Allele
Frequencies when Considering only 1 Locus). E.g., Consider a
Population of Pueblo Indians Scored for the MN Blood Group Type
Blood Type
M
MN
N
Sum
Genotype
MM
MN
NN
Number
83
46
11
140
(2*11+46)/280
= 0.24
1
Allele (Gamete
Type)
M
Allele Freq.
(2*83+46)/280
= 0.76
N
Gene Pools are Characterized by Gamete Frequencies (Allele
Frequencies when Considering only 1 Locus). E.g., Consider a
Population of Australian Aborigines Scored for the MN Blood
Group Type
Blood Type
M
MN
N
Sum
Genotype
MM
MN
NN
Number
9
113
250
372
(2*250+113)/744
= 0.824
1
Allele (Gamete
Type)
M
Allele Freq.
(2*9+113)/744
= 0.176
N
6
Gene Pool (Alternative
Definition)
A Gene Pool is the population of
potential gametes that can be
produced by the individuals of a
deme.
The Gene Pool As a Population
of Potential Gametes



Gametes are the bridge from one
generation to the next
This definition emphasizes the genetic
continuity over time of a deme
This definition is more useful in
evolutionary theory
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Demes and Gene Pools
 Meiosis
Interconnects the Deme to the
Gene Pool
 Therefore, Given Mendel’s Laws and
Normal Meiosis, You Can Always
Calculate the Allele Frequencies in the
Gene Pool From the Genotype
Frequencies in the Deme
Demes and Gene Pools:
Pueblo Indian Deme
MM
0.59
diploid
Meiosis
haploid
Mendelian
Probabilities
In Meiosis
MN
0.33
1
1/
2
1/
M
1(0.59) + 1/2(0.33) = 0.76
NN
.08
1
2
N
1(.08) + 1/2(.33) = .24
Pueblo Indian Gene Pool
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Demes and Gene Pools:
MM
0.024
MN
0.304
diploid
Meiosis
haploid
Australian Aborigine Deme
1
1/
2
M
1(.024) + 1/ 2(.304)
= 0.176
NN
0.672
Mendelian
Probabilities
In Meiosis
1/
1
2
N
1(0.672) + 1/2(0.304) = 0.824
Australian Aborigine Gene Pool
Demes with the Same Alleles Can Have Gene
Pools With Different Allele Frequencies:
Pueblo Indians
M
0.76
N
0.24
Australian Aborigines
M
0.176
N
0.824
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Evolution




Is a change in the frequency of alleles or
allele combinations over space and time in
the gene pool of a reproducing population
Is a process that is manifest only at the
level of a reproducing population
Can never be understood in terms of
individuals alone.
Requires Genetic Variation
Importance of Mutation


If DNA replication were 100% accurate,
there would be no possibility of genetic
change over time: NO EVOLUTION
Mutation is the ultimate source of all
genetic variation
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DNA Can Mutate & Recombine
Occurs at the molecular level
before the informational content of
DNA is expressed; Hence,
mutation is “random” with respect
to the needs of the individual in
coping with its environment.
Proof of Randomness - Replica Plating
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“Randomness” Means Mutations Have a Broad
Spectrum of Impacts on Their Bearers
Neutral
Unfavorable
Favorable
Effects of 50 Spontaneous Mutation Lines Derived from
a Strain of Yeast Growing in a Laboratory Environment.
Mutation Creates Allelic Variation
Recombination and Diploidy Amplify It





E.g., We now know of 12,000,000 single nucleotide
polymorphisms (SNPs), most of which are bi-allelic
and can form 3 genotypes each.
Recombination Can Produce 103612360 Gametic
Combinations of These 24 million Alleles
These Gametes Can Create 105725455 Genotypes
There are 6 ×109 Humans In the World
There are 1080 Electrons in the Universe
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High Genetic Variation Implies:
Each Individual Is Unique
 Evolution Can Occur

Basic Premises of Population Genetics



DNA can replicate
DNA can mutate and recombine
DNA encodes information that interacts
with the environment to influence
phenotype
A phenotype is a measurable trait of an individual.
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Is DNA the “Blueprint of Life”
The brain has 1011 neurons &
1015 connections. There is not
Enough information storage
Capacity in the 3 billion bp in
The human genome to encode
A blueprint for such a structure.
Is DNA the “Blueprint of Life”
DNA does not provide phenotypic blueprints; instead the
information encoded in DNA controls dynamic processes (such
as axonal growth patterns and signal responses) that always
occur in an environmental context. There is no doubt that
environmental influences have an impact on the number and
pattern of neuronal connections that develop in mammalian
brains in general. It is this interaction of genetic information
with environmental variables through developmental
processes that yield phenotypes. Genes should never be
equated to phenotypes. Phenotypes emerge from genetically
influenced dynamic processes whose outcome depends upon
environmental context.
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Is DNA the “Blueprint of Life”
Proboscis
Mouth
Uterus
DNA encodes information that interacts with
the environment to influence phenotype
Among The Traits That Can Be Influenced By
Genetically Determined Responses to the
Environment Are:
1.
The Viability in the Environment
2.
Given Alive, the Mating Success in the
Environment
3.
Given Alive and Mated, Fertility or
Fecundity in the Environment.
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Physical Basis of Evolution



DNA can replicate
DNA can mutate and recombine
DNA encodes information that
interacts with the environment to
influence phenotype
Viability
Mating Success
Fecundity/Fertility
These Are Combined Into A Single
Phenotype of Reproductive Success
Or FITNESS
Methodological Approaches in
Population Genetics




Reductionism
Holism
Comparative analysis
Monitoring of natural populations
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Reductionism
Reductionism seeks to break down a complex whole into simple
parts to find underlying rules, laws and explanations.
Reductionism assumes that many complex features of a system
can be explained in terms of a few components or rules contained
within the system itself; that is, complexity lies within the
content of the system.
In this manner, simplicity (the parts contained within the system)
generates complexity (the attributes of the whole system).
Reductionism seeks necessary and sufficient explanations for the
phenomenon under study. Such content-oriented explanations
are said to be proximate causes for the phenomenon of interest.
Reductionism
E.g., beaks in Darwin’s finches on the Galapagos Islands
show much variation in length, depth and width.
Experiments in chick embryos
reveal that beak length is
controlled by the degree of
P4
BM
expression of CaM (a Ca2+binding protein that is a key
component of a Ca2+ dependent
signal transduction pathway)
CaM
and beak depth/width by bone
morphogenetic protein 4
(BMP4) expression (Abzhanov, A. et al. Nature 442, 563-567 (2006)).
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Holism
The holistic approach is based upon the assumption that simple
patterns exist in nature that emerge when underlying complex
systems are placed into a particular context (simplicity
emerges from complexity).
The explanation of these emergent patterns often does not
depend upon knowing the detailed content of the component
systems, but rather depends upon the context in which these
components are placed in a higher level interacting whole.
These context-dependent explanations that do not depend upon
detailed content reveal what is commonly called ultimate
causation.
Holism
E.g., beaks in Darwin’s finches on the Galapagos Islands
show much variation in length, depth and width.
Beaks are used to secure and ingest food. Hypothesize that the
feeding habits determine beak length, depth and width.
Therefore, expect correlation between feeding habits and beaks
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Holism
1.0
0.8
0.6
0.4
0.2
0.0
1
2
3
4
5
6
1
Seed Depth in mm
Comparative Analysis
Populations (and the genes within them) have a history. The
comparative approach to biological science uses this history.
An evolutionary tree is constructed for a group of species or for the
genetic variation within a species.
Then other data are overlaid upon the evolutionary tree to infer
when evolutionary transitions occurred and patterns of evolutionary
associations among characters.
Contrasts between those organisms on either side of a transitional
branch are those that are most informative because the sharing of
evolutionary history for all other traits is maximized by this
contrast.
A comparative contrast bears some similarity to a controlled
experiment in reductionistic empirical science because the contrast
is chosen to minimize confounding factors.
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Comparative Analysis
The evolutionary tree indicates that the beak
diversity arose from a common ancestor on the
Galapagos islands. The tree indicates which
species would be most informative in both
holistic and reductionistic studies.
Comparative Analysis
(Abzhanov, A. et al. Nature 442, 563-567 (2006)).
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Monitoring Natural Populations
Many hypotheses in population genetics can be tested by
monitoring natural populations.
One of the simplest types of monitoring is a one-time
sample of individuals of unknown relationship coupled with
some sort of genetic survey.
The monitoring of natural populations can be extended
beyond a simple one-time survey of genetic variation of
individuals of unknown relationship. For example, one can
sample families (parents and offspring) instead of
individuals, or follow a population longitudinally through
time to obtain multi-generation data.
Monitoring Natural Populations
11.0
1978
1976
10.0
9.0
8.0
8.0
9.0
10.0
11.0
Midparent Beak Depth (mm)
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Monitoring Natural Populations
Population genetics is concerned with the fate of genes over
space and time within a species, and this fate can be
observed or estimated by monitoring populations over space
and time.
Such monitoring over space and time also allows population
geneticists to make use of natural experiments. For
example, natural selection arises out of how individuals
interact with their environment, but environments
themselves often change over space and time. Although not
a controlled experiment in the strict reductionist sense,
spatial and temporal environmental contrasts can sometimes
provide a similar inference structure.
Monitoring Natural Populations
Large
and Hard
6.0
5.0
4.0
Small
and Soft
Jul
Oct Jan Apr
1975
Jul
1976
Oct Jan Apr
Jul
1977
Oct Jan Apr Jul
Oct Jan
1978
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Monitoring Natural Populations
1976
Mean
90
1978
Mean
Mean 1976
30
Finches Hatched
in 1976
20
60
1976 Daphne Birds
N=741
30
Mean 1978
10
0
6
7
8
9
10
12
11
12
13
14
1978 Daphne Survivors
N=90
8
40
Finches Hatched
in 1978
30
20
4
10
6
7
8
9
10
11
Beak Depth (mm)
12
13
14
0
7.3
7.8
8.3 8.8 9.3 9.8 10.3 10.8 11.3
Beak Depth (mm)
Methodological Approaches in
Population Genetics




Reductionism
Holism
Comparative analysis
Monitoring of natural populations
The best studies in population genetics tend to integrate
multiple methods of inference that are complementary and
reinforcing to one another.
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