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Populations Genetic Polymorphism

• Group of individuals of the same species that can
interbreed with one another
• Some species occupy a wide geographic range and
are divided into discrete populations
• Genetic polymorphism provides a much
greater source of genetic variation than do the
relatively few new mutations that arise in
each generation

Polygenic Inheritance Continuous Variation

• Polygenic inheritance, also known as quantitative
or multifactorial inheritance, refers to inheritance • Small heritable
of a phenotypic characteristic (trait) that is changes provide most
attributable to two or more genes, or to the
interaction with the environment, or both of the variation on
which natural
• Unlike monogenic traits, polygenic traits do not
follow patterns of simple Mendelian inheritance selection acts
(discontinuous traits)
• Instead, their phenotypes typically vary along a
continuous gradient depicted by a bell-shaped
curve (a normal distribution) FHeights of 1,000 Harvard College
students aged 18 to 25
Adapted from Castle, W. E. Genetics and Eugenics, Fourth
edition. Harvard University Press, 1932.

Continuous Variation Gene Pool

• The gene pool is all of the
genes and different alleles
in a population
• We study genetic variation
within the gene pool and
how genetic variation
changes from one
generation to the next

It is almost impossible for a single gene Emphasis is often on variation in alleles between
members of a population at certain loci of interest
locus to control continuous variation

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Genes in Natural Populations Are Usually
Polymorphic
• Polymorphism – many phenotypic traits display variation
within a population
– Due to 2 or more alleles at a locus that influence a phenotype
• Polymorphic gene/locus - 2 or more alleles
• Monomorphic gene/locus– predominantly a single allele
[“fixed” locus]
• Single nucleotide polymorphism (SNPs)
– Smallest type of genetic change in a gene; a point mutation
– Most common – 90% of the variation in human gene sequences
• Large, healthy populations exhibit a high level of genetic
diversity
• Polymorphisms are the raw material for evolution
Allele Frequencies
• A population’s gene pool includes all the alleles
for all the loci present in the population
• Diploid organisms have a maximum of two
different alleles at each genetic locus
• Typically, a single individual therefore has only a
small fraction of the alleles for a given locus that
are present in the population as a whole
Five Agents of Evolutionary Change
A population not in Hardy-Weinberg equilibrium is one in
which allele frequencies are changing generation to
generation due to one or more of the five evolutionary agents
that are operating in the population 11
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Population Genetics and Gene (Allele)
Frequencies in Populations
• The Neo-Darwinian theory
– Evolution is a population phenomenon
– Evolution is a change in gene (now allele) frequencies
in a population because of various natural forces such
as mutation, selection, migration, or genetic drift
– These changes in allele frequencies lead to differences
among populations, species, and higher clades
– This population genetics view of evolution became
known as Neo-Darwinian theory with its emphasis on
the frequency of genes and alleles in populations
The Hardy-Weinberg Principle
Godfrey H. Hardy: English mathematician (1903)
Wilhelm Weinberg: German physician (1908)
W.E. Castle: American geneticist (1908) (left out)
Working independently just a few years after the
rediscovery of Mendelian genetics they concluded
that:
The original proportions of the allele frequencies in a
population remain constant from generation to
generation as long as five assumptions are met 10
Agents of Evolutionary Change
• Small Population Size:
• When a population is large, then allele frequencies are very
unlikely to change due to random sampling error
• When a population is small, then, just by chance, some individuals
fail to mate at all, not because they are unfit
• When a population is small, then, just by chance, some offspring
fail to survive to reproduce, not because they are unfit
• When a population is small, gene frequencies may change due to
these sorts of random effects – this is called genetic drift
California condors
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Numbers of brown (bw75) alleles in 107

Genetic Drift Genetic Drift populations of D. melanogaster

• Genetic drift: Random fluctuations in allele • In small populations, allele frequency

changes that have no predictable constancy
frequencies over time due to chance events or direction from generation to generation
• important in small populations • Genetic drift is a consequence of random
fluctuations in gene frequencies that arise in
• founder effect – a few individuals small populations
found a new population (with a • In this experiment, 107 populations were
small allelic pool) established with p = q = 0.5 for brown
(bw/recessive) and red (+/wildtype/
• bottleneck effect – a drastic dominant) eye alleles, but at each
reduction in population, and generation, only 16 parents were drawn, at
gene pool size and complexity random, to produce the next generation (+/+) (bw/bw)
• By generation 19, brown eye had been
DNA studies indicate that polar bears have suffered repeated bottleneck eliminated from 30 populations and fixed at
events when the arctic climate warmed and also repeated hybridization
13 Data from Buri, P., Evolution 10 (1956): 367-402.

causing gene introgression from their sister group, the brown bears 100% in another 28 populations.

Definitions of Genetic Drift and Comments Agents of Evolutionary Change

on Them
• Random Mating is required for the Hardy-Weinberg
Equilibrium
• The members of the population mate with each other without
regard to their phenotypes and genotypes
• The members of the population are (relatively) equally likely to
mate with any other member of the population of the opposite
sex, i.e., have relatively equal access to all members of the
population
• Humans mate without regard to ABO and Rh blood types
– This example shows that a particular gene can meet the H-W equilibrium
criteria, even though the specie as a whole does not
• Wind-pollinated plant species and many aquatic species who
Regardless of the definition, genetic drift tends to increase variation release their eggs and sperm into the water
between populations, but in no particular direction, including not • Animals who are members of larger herds or flocks
necessarily to increase the fitness of the population
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Agents of Evolutionary Change Agents of Evolutionary Change

• Nonrandom Mating: mating between specific • Classification of mating systems
genotypes shifts genotype frequencies – Monogamy, polygamy, polyandry
(Darwin 1871)

– Self pollination/fertilization
– Asexual reproduction
• Apomixis: parthenogenesis in animals
and apogamy in plants

Non-Random mating could be either like

with like; also called Assortative Mating or
opposites attracting each other; also
17 18
called Non-Assortative Mating

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Agents of Evolutionary Change

Inbreeding
• Nonrandom Mating: mating between specific
genotypes shifts genotype and phenotype frequencies
– Assortative Mating: does not change frequency of individual
alleles; increases the proportion of homozygous individuals • Mating between relatives or (selfing in plants)
– Disassortative Mating: phenotypically different individuals – Inevitable in smaller populations
mate; produces an excess of heterozygotes
– Occurs in nature because of proximity of relatives –
Assortative Mating Disassortative Mating example: natural stands of tree whose relatives are
Selfing Inbreeding Random Mating Obligate Outcrossing nearby because of limited seed dispersion
• If there is no natural selection, an inbreeding
Less Genetic Diversity Hardy-Weinberg More Genetic Diversity population will acquire an increase in the
More Homozygotes Equilibrium More Heterozygotes
Clones/Clonal Lineages Many Genotypes frequency of homozygotes without a change in
More Uniformly Fit Individuals Individuals of Varying Fitness
Less Potential to Adapt to Change More Potential to Adapt to Change 19
allele frequency in the population

Agents of Evolutionary Change • Breakage of a chromosome can lead to four

types of changes in chromosome structure.
• Mutation: Changes in a cell’s DNA • A deletion occurs when a chromosome
fragment lacking a centromere is lost during
– Mutation is the ultimate source of cell division.
genetic variation – This chromosome will be missing certain genes.
– Since a new mutation transforms an
allele into a different allele, it must • A duplication occurs when a fragment
also change allele frequencies becomes attached as an extra segment to a
– Mutation rates are generally so low sister chromatid.
that they have little effect on
Hardy-Weinberg proportions of
common alleles in the short term
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• An inversion occurs when a chromosomal Agents of Evolutionary Change

fragment reattaches to the original
chromosome but in the reverse orientation. • Mutation: Changes in a cell’s DNA
• In translocation, a chromosomal fragment joins – Mutations are usually deleterious
a nonhomologous chromosome. Stumpy
– Some translocations are reciprocal, others are not.

Stumpy, born 2007, in UK,

on a duck farm, who
eventually lost the two
extra legs to accidental
traumas, and his
companion, Alice
24

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Agents of Evolutionary Change Agents of Evolutionary Change

• Gene Flow: A movement of alleles from one
• Natural selection: environmental conditions
determine which individuals in a population
produce the most offspring
• Three conditions are required for natural
selection to occur:
– Variation must exist among individuals in a
population
– Variation among individuals must result in differences
in the number of offspring surviving
– Variation must be genetically inherited
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population to another
– Migration of individuals or gametes between
populations
– Migration can be a powerful agent for evolutionary
change
– Migration tends to homogenize allele frequencies
between populations
– But migration is adding or removing alleles from
the gene pool, so migration is going to change gene
frequencies in the populations experiencing
immigration or emigration
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Agents of Evolutionary Change Hardy-Weinberg Equation

Migration – the movement of breeding individuals into or
out of isolated populations – results in evolutionary change
because alleles move with the individuals. We call this
movement gene flow.
• If enough migration occurs, the original isolates, with
their inherent limited genetic variability, may fuse and
form a new larger population with increased genetic
variability.
• Relates allele and genotype frequencies under
certain conditions
• p2 + 2pq + q2 = 1
• p = frequency of the dominant allele
• q = frequency of the recessive allele
– The genotype frequencies of a population are
– p2 is frequency of homozygous dominant genotype
– 2pq is frequency of heterozygous genotype
– q2 is frequency of homozygous recessive genotype

Hardy–Weinberg Principle The Hardy-Weinberg Equilibrium

If a population meets all the assumptions of the Hardy-
According to the Hardy–
Weinberg principle, in a Weinberg Principle, then allele frequencies in the
population of randomly population will remain constant through future generations
mating individuals, allele
1. The population size is very large (no genetic drift)
frequencies are
conserved and in 2. Random mating is occurring
equilibrium unless 3. No mutation occurs
external forces act on 4. No selection occurs
them 5. No alleles transfer in or out of the population (no migration)

Hardy–Weinberg
equilibrium
A population in true Hardy-Weinberg equilibrium
is rarely seen in nature!

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Sickle-Cell Anemia Sickle Cell Anemia

• In sickle-cell anemia, hemoglobin (Hbs) has poor
oxygen affinity
• Sequencing of the hemoglobin gene revealed one
change from the normal amino acid sequence:
Normal globin gene (H)
GAG (glutamate)
Hh Hh HH hh Hh

GTG (valine) Genotypes

Sickle cell gene (h)

Sickle-Cell Anemia Sickle cell anemia

Evolution of populations is best understood
in terms of frequencies: • About 1% of West Africans have sickle cell
1. Phenotypes 2. Alleles 3. Genotypes anemia.
Phenotypes Gene Alleles Genotypes
• A single mutation causes a valine amino acid
Normal hemoglobin
to replace a glutamic acid in the alpha chain of
H HH, Hh
hemoglobin hemoglobin

Sickle Cell hemoglobin h hh • The mutation causes hemoglobin molecules to

stick together.

Why isn’t sickle cell allele eliminated

by selection?
• Only individuals homozygous for the allele get
sickle cell anemia.
• Individuals with only one copy of the allele
(heterozygotes) get sickle cell trait (a mild
form of the disease)
• Individuals with the sickle cell allele (one or
two copies) don’t get malaria.

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Heterozygote advantage Heterozygote advantage

• Heterozygotes have higher survival than either
homozygote (heterozygote advantage).
• Sickle cell homozygotes die of sickle cell
anemia, many “normal” homozygotes die of
malaria.
• Stabilizing selection thus favors sickle cell
allele.
• A heterozygote advantage (or overdominance)
results in a balanced polymorphism in a
population.
• Both alleles are maintained in the population
as the heterozygote is the best combination of
alleles and a purely heterozygous population
is not possible.

Overdominance
Overdominance
• Strong selection is acting, but the allele frequencies did
Surprising things happen when the heterozygote is most fit. not change.
This example uses pA = pa = 0.5. • The population is at an equilibrium state.

Genotype black/black (AA) black/red (Aa) red/red (aa) • If the initial frequencies were not 50/50, the population
Fitness 0.8 1.0 0.8 would move towards 50/50 and then stick there.
Before selection 0.25 0.5 0.25
Death due to sel. 0.05 0.0 0.05 • The ratio 50/50 is because the homozygotes are equally
After selection 0.2/0.9 0.5/0.9 0.2/0.9 bad.
After selection 0.22 0.56 0.22 • If they were unequally bad, a different ratio would be
obtained
New allele frequencies:
pA = 0.5
pa = 0.5

Overdominance Overdominance
The classic sickle cell case may have selection • The classic sickle cell case may have selection approx. like
approximately like this (in the presence of this (in the presence of malaria).
Starting with pA=0.6:
malaria):
• Genotype AA AS SS
• Genotype AA AS SS • Fitness 0.8 1.0 0.0
• Fitness 0.8 1.0 0.0 • Before sel. 0.36 0.48 0.16
• If we start with pA=0.6, what are the genotype • Death due to sel. 0.07 0.0 0.16
• After selection 0.29/0.77 0.48/0.77 0.0/0.77
frequencies in adults (after selection) next
• After selection 0.38 0.62 0.00
generation? What are the new allele
frequencies. pA=0.69, so it's increasing.

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Population Bottlenecks and Founder Effect Founder Effect Example

• Bottlenecks and the founder effect are closely
related phenomena.
• Founder effect: If a small group of individuals
leaves a larger population and develops into a
separate, isolated population, the allele
frequencies in the new population are
determined by the allele frequencies in the
founders.
• This is especially true for rare alleles, which can
suddenly become prominent if one of the
founders has the rare allele.
• Founder effect example: the Amish are a group
descended from 30 Swiss founders. Most Amish
mate within the group. One of the founders had
Ellis-van Crevald syndrome, which causes short
stature, extra fingers and toes, and heart
defects. Today about 1 in 200 Amish are
homozygous for this syndrome, which is very
rare in the larger US population.
• The problem comes from this recessive
condition becoming homozygous due to the
mating of closely related people.

Human Bottleneck Rare Alleles and Eugenics

• The human population is • A popular idea early in the 20th century was
“eugenics”, improving the human population
thought to have gone through a through selective breeding. The idea has
population bottleneck about been widely discredited, largely due to the
100,000 years ago. There is evils of “forced eugenics” practiced in
certain countries before and during World
more genetic variation among War 2.
chimpanzees living within 30
miles of each other in central • The problem with sterilizing “defectives” is
Africa than there is in the entire that most genes that produce a notable
genetic diseases are recessive. If you only
human species. sterilize the homozygotes, you are missing
• The tree represents mutational the vast majority of people who carry the
allele.
differences in mitochondrial
DNA for various members of the • Assume that the frequency of a gene for a
Great Apes (including humans). recessive genetic disease is 0.001. Thus p =
0.999 and q = 0.001. Thus p2 = 0.998, 2pq =
0.002, and q2 = 0.000001. The ratio of
heterozygotes (undetected carriers) to
homozygotes (diseased) is 2000 to 1

Nazi Eugenics

"The Threat of the Underman.

It looks like this: Male criminals
had an average of 4.9 children,
criminal marriage, 4.4 children,
parents of slow learners, 3.5
children, a German family 2.2
children, and a marriage from
Thanks
the educated circles, 1.9
children."