POPULATION GENETICS (BLS 401)

Course Content:
1. Introduction– Population genetics, the general features of populations and gene pools, genes in
populations and the Hardy-Weinberg Equation

2. Classical Ecological Genetics & Polymorphism– phenotypic & genotypic polymorphisms,

transient polymorphism, balanced polymorphisms. Polymorphic and monomorphic genes at the
population level

3. Allele and Genotype Frequencies– Defining allele and genotype frequencies from molecular data,
changes in allele frequencies. Deriving genotypic & allelic frequencies, factors that change allele and
genotype frequencies in a population

4. Practicals – Calculating allelic frequencies, assumptions of Hardy-Weinberg equilibrium, proof of

Hardy-Weinberg equilibrium, Generation time, testing for fit to Hardy-Weinberg equilibrium

5. Random & Non-random mating – positive & negative assortative mating, role in population size
& change in gene frequency.

6. Inbreeding & outbreeding- inbreeding co-efficient, genotype frequencies under inbreeding, uses
& effects of inbreeding in farm animals, genetic consequences of inbreeding, reasons for inbreeding.

7. Random Genetic drift – definition, its effects in small & large populations, bottlenecking &
founder effect, genetic drift simulation, genetic drift vs selection.

8. Genetic equilibrium – definition, conditions for its stability, deviation of it (evolution).

9. Selection – overview, types & subtypes, negative & positive selections, patterns of selection
(stabilizing, disruptive, directional, balancing), mechanisms of selection (disassortative sexual
selection, frequency dependent selection), overdominance, natural selection, artificial selection, and
ecological selection.

10. DNA Fingerprinting & Paternity Test

NOTE: Upon completion of BLS 401, students should be able to (1) understand the concept of a
population and polymorphism in populations, (2) apply Hardy-Weinberg equation to calculate the
frequency of alleles and genotypes in a population, (3) understand the factors that change allele
frequencies in a population and how they influence H-W equilibrium and (4) know the various
mechanisms by which organisms acquire new genetic variations.

Recommended Texts:

1. Principles of Population Genetics by Hartle D.L., Andrew G. Clark (4th edition)

2. Introduction to Genetic Analysis by Griffiths et al. (11th edition)
3. Genetics – Analysis & Principles by Robert J. Brooker (4th edition)
INTRODUCTION:

Mendelian genetics and the use of Punnett squares allow us to predict what the genotype of the
offspring of two individuals would be. Now that you know more about genes within individuals (the
relationship between genes and the individual) and their family members, we can proceed to study
genes in a population or species. This course explores the bigger picture of population genetics. In the
first section we explore some of the general features of populations and gene pools, as well as the
mathematical calculations of allele and genotype frequencies.

The Hardy-Weinberg law of genetic equilibrium provides a mathematical model for studying
evolutionary changes in allelic frequency within an entire population, rather than the offspring of a
particular pair of parents. When we look at entire populations, we may ask how can O be the most
common of the blood types if it is a recessive trait? Or if Huntington’s disease is a dominant trait,
shouldn’t three-fourths of the population have Huntington’s while one-fourth have the normal
phenotype? Shouldn’t recessive traits be gradually “swamped out” so they disappear from the
population? We will use the Hardy-Weinberg Model of population genetics to examine these questions.

Population = A group of interbreeding individuals of the same species sharing a common geographical
area/that share a gene pool

Species = "A group of populations that have the potential to interbreed in nature and produce viable
offspring"

Evolution = "Changes in gene frequencies in a population over time". Evolution takes place at the
population, not individual level. i.e. populations, not individuals evolve

Gene pool = Sum total of all the alleles within a population

Processes of evolution:

1. Mutation - changes in nucleotide sequences of DNA. Mutations provide new alleles,

and therefore are the ultimate source of variation
2. Recombination - reshuffling of the genetic material during meiosis (prophase I &
metaphase I)
3. Natural Selection - differential reproduction (discussed below)
4. Reproductive isolation (discussed shortly)
5. Migration and Gene flow-

Mutation and recombination provide natural variation, the raw material for evolution.

The field of population genetics is concerned with changes in genetic variation within a group of
individuals over time. Population geneticists want to know the extent of genetic variation within
populations, why it exists, and how it changes over the course of many generations. The field of
population genetics emerged as a branch of genetics in the 1920s and 1930s. Its mathematical
foundations were developed by theoreticians who extended the principles of Gregor Mendel and
Charles Darwin by deriving formulas to explain the occurrence of genotypes within populations. These
foundations can be largely attributed to three scientists: Sir Ronald Fisher, Sewall Wright, and J.B.S.
Haldane. As we will see, support for their mathematical theories was provided by several researchers
who analyzed the genetic composition of natural and experimental populations. More recently,
population geneticists have used techniques to probe genetic variation at the molecular level. In
addition, staggering advances in computer technology have aided population geneticists in the analysis
of their genetic theories and data. In this class, we will explore the genetic variation that occurs in
populations and consider the reasons why the genetic composition of populations may change over the
course of several generations.

In most organisms, matings are not under the control of the investigator, and the familial relationships
among individuals are unknown. This situation is typical of the studies of organisms in their natural
habitat. Most organisms live in populations of individuals, and the genealogical relationship between
one individual and the next is obscure. At first it might seem that classical genetics with its simple
Mendelian ratios could have little to say about such complex situations, but this is not the case. The
principles of Mendelian genetics can be used both to interpret data collected in natural populations and
to make predictions about the genetic composition of populations. Application of genetic principles to
entire population of organisms constitutes the subject of population genetics.

GENES IN POPULATIONS, AND THE HARDY-WEINBERG EQUATION

Population genetics is a direct extension of our understanding of Mendel’s laws of inheritance,

molecular genetics, and the ideas of Darwin. In the field of population genetics, the focus shifts away
from the individual and toward the population of which the individual is a member. Conceptually, all
of the alleles of every gene in a population make up the gene pool. In this regard, each member of the
population is viewed as receiving its genes from its parents, which, in turn, are members of the gene
pool. Furthermore, individuals that reproduce contribute to the gene pool of the next generation.
Population geneticists study the genetic variation within the gene pool and how such variation changes
from one generation to the next. The emphasis is often on allelic variation.

A Population Is a Group of interbreeding Individuals That Share a Gene Pool

The term population in genetics has a very specific meaning. For sexually reproducing species, a
population is a group of individuals of the same species that occupy the same region and can interbreed
with one another. Many species occupy a wide geographical range and are divided into discrete
populations. For example, distinct populations of a given species may be located on different
continents, or a geographical feature such as a large mountain range could divide populations on the
same continent. Sometimes the area is large, as when we refer to the population of sparrows in Africa;
it may even include the entire earth, as when we speak of the “human population.” More commonly,
the area is considered to be of a size within which individuals in the population are likely to find mates.
Many geographically widespread species are subdivided into more or less distinct breeding groups,
called subpopulations, which live within limited geographical areas. Each subpopulation is a local
population. The complete set of genetic information contained within the individuals in a population is
called the gene pool. The gene pool includes all alleles present in the population.

A large population usually is composed of smaller groups called local populations or demes. The
members of a local population are far more likely to breed among themselves than with other members
of the general population. Local populations are often separated from each other by moderate
geographical barriers, for example a wide river could separate two groups of a tree. Trees on opposite
sides of this river constitute local populations. Breeding is much more apt to occur among members of
each local population than between members of neighboring populations. On relatively rare occasions,
however, pollen can be blown across the river, which allows breeding between these two local
populations.

Populations typically are dynamic units that change from one generation to the next. A population may
change its size, geographical location, and genetic composition. With regard to size, natural
populations commonly go through cycles of “feast or famine,” during which the population swells or
shrinks. In addition, natural predators or disease may periodically decrease the size of a population to
significantly lower levels; the population may later rebound to its original size. Populations or
individuals within populations may migrate to a new site and establish a distinct population in this
location. The environment at this new geographic location may differ from the original site. What are
the consequences of such changes? As population sizes and locations change, their genetic
composition generally changes as well. A major interest for population geneticists is to develop
mathematical theories that predict how the gene pool will change in response to fluctuations in size,
migration, and new environments.

Polymorphic and Monomorphic Genes at the Population Level

In population genetics, the term polymorphism (meaning many forms) refers to the observation that
many traits display variation within a population. Historically, polymorphism first referred to the
variation in traits that are observable with the naked eye. Polymorphisms in color and pattern have
long attracted the attention of population geneticists. These include studies involving brown, pink, and
yellow land snails.

What is the underlying cause of polymorphism? At the DNA level, polymorphism may be due to two
or more alleles that influence the phenotype of the individual that inherits them. In other word, it is due
to genetic variation. The term polymorphism is also used to describe a gene that commonly exists as
two or more alleles in a population. By comparison, a monomorphic gene exists predominantly as a
single allele in a population. By convention, when a single allele is found in at least 99% of all cases,
the gene is considered monomorphic. (Some geneticists view an allele frequency of 95% or greater to
be monomorphic.)

At the level of a particular gene, a polymorphism may involve various types of changes such as a
deletion of a significant region of the gene, a duplication of a region, or a change in a single nucleotide.
This last phenomenon is called a single nucleotide polymorphism (SNP). SNPs are the smallest type of
genetic change that can occur within a given gene, and are also the most common. In humans, for
example, SNPs represent 90% of all the variation in DNA sequences that occur among different people.
SNPs are found very frequently in genes. In the human population, a gene that is 2,000 to 3,000 bp in
length will, on average, contain 10 different sites that are polymorphic. The high frequency of SNPs
indicates that polymorphism is the norm for most human genes. Likewise, relatively large, healthy
populations of nearly all species exhibit a high level of genetic variation as evidenced by the
occurrence of SNPs within most genes.

Within a population, the alleles of a given gene may arise by different types of genetic changes. The
figure below considers a gene that exists in multiple forms in humans. This example is a short segment
of DNA found within the β-globin gene. The top sequence is an allele designated HbA, whereas the
middle sequence is called HbS. These alleles differ from each other by a single nucleotide, so they are
an example of a single nucleotide polymorphism. The HbS allele causes sickle-cell disease in a
homozygote. The bottom sequence contains a short, 5 bp deletion compared to the other two alleles.
This deletion results in a nonfunctional β-globin polypeptide. Therefore, the bottom sequence is an
example of a loss-of-function allele.

Figure 1 (By RJ Brooker) The relationship between alleles and various types of mutations. The DNA
sequence shown here is a small portion of the β-globin gene in humans. Mutations have altered the gene to
create the three different alleles in this figure. The top two alleles differ by a single base pair and are referred to
as a single-nucleotide polymorphism (SNP). The bottom allele has a 5-bp deletion that begins right after the
arrowhead. The deletion results in a non-functional polypeptide. It is a loss-of-function allele.

ALLELE AND GENOTYPE FREQUENCIES

Understanding the prevalence of polymorphic genes within populations is of great importance to

population geneticists. Much of our work evaluates the frequency of alleles in a quantitative way.
Two fundamental calculations are central to population genetics: allele frequencies and genotype
frequencies. Allele frequencies are the percent that an allele is represented in a population; while
Genotype frequencies represent the percent of individuals that are homozygous recessive, homozygous
dominant or heterozygous in a population.
The allele and genotype frequencies are expressed as:

Number of copies of an allele

in a population
Allele frequency =
Total number of all alleles for that
gene in a population

Number of individuals with a

particular genotype in a population
Genotype frequency =
Total number of individuals in a
population

Though these two frequencies are related, a clear distinction between them must be kept in mind. As
an example, let’s consider a population of 100 pea plants with the following genotypes:

64 tall plants with the genotype TT

32 tall plants with the genotype Tt
4 dwarf plants with the genotype tt
When calculating an allele frequency, homozygous individuals have two copies of an allele, whereas
heterozygotes have only one. For example, in tallying the t allele, each of the 32 heterozygotes has one
copy of the t allele, and each dwarf plant has two copies. The allele frequency for t equals

32 + 2(4)
t =
2(64) + 2(32) + 2(4)

40
= = 0.2, or 20%
200

This result tells us that the allele frequency of t is 20%. In other words, 20% of the alleles for this gene
in the population are the t allele.
Let’s now calculate the genotype frequency of tt (dwarf plants):

4
tt =
64 + 32 + 4

4
= = 0.04, or 4%
100
We see that 4% of the individuals in this population are dwarf plants.
Allele and genotype frequencies are always less than or equal to 1 (i.e., ≤100%). If a gene is
monomorphic, the allele frequency for the single allele will equal or be close to a value of 1.0. For
polymorphic genes, if we add up the frequencies for all of the alleles in the population, we should
obtain a value of 1.0. In our frog example, the allele frequency of g equals 0.2. The frequency of the
other allele, G, equals 0.8. If we add the two together, we obtain a value of 0.2 + 0.8 = 1.0.

Random Mating and the Hardy-Weinberg Principle

Random mating is by far the most prevalent mating system for most species of animals and plants,
except for plants that regularly reproduce through self fertilization. In random mating, each type of
mating pair is formed as often as would be expected through chance encounters between the genotypes.

With random mating, the relationship between allele frequency in one generation and genotype
frequency in the next generation is particularly simple because random mating of individuals is
equivalent to random union of gametes. Conceptually, we may imagine all the gametes of a population
as present in a large container. To form zygote genotypes, pairs of gametes are withdrawn at random
from the container.

The Hardy-Weinberg Equation Can Be Used to Calculate Genotype Frequencies Based on Allele
Frequencies

Now that we have a general understanding of genes in populations, we can begin to relate these
concepts to mathematical expressions as a way to examine whether allele and genotype frequencies
will change over the course of many generations. In 1908, a British mathematician, Godfrey Harold
Hardy, and a German physician, Wilhelm Weinberg, independently derived a simple mathematical
expression that predicted stability of allele and genotype frequencies from one generation to the next.
It is called the Hardy-Weinberg equilibrium, because (under a given set of conditions) the allele and
genotype frequencies do not change over the course of many generations.

This relationship establishes a framework on which to understand changes in allele frequencies within a
population when such an equilibrium is violated. Why is the Hardy-Weinberg equilibrium a useful
concept? An equilibrium is a null hypothesis, which suggests that evolutionary change is not occurring.
In reality, however, populations rarely achieve an equilibrium. Therefore, the main usefulness of the
Hardy-Weinberg equilibrium is that it provides a framework on which to understand changes in allele
and genotype frequencies within a population when such an equilibrium is violated. To appreciate the
Hardy-Weinberg equilibrium, let’s return to our hypothetical pea plant example in which a gene is
polymorphic and exists as two different alleles, T and t. If the allele frequency of T is denoted by the
variable p, and the allele frequency of t by q, then
p+q=1

For example, if p = 0.8, then q must be 0.2. In other words, if the allele frequency of T equals 80%, the
remaining 20% of alleles must be t, because together they equal 100%.

The Hardy-Weinberg equation is used to relate allele frequencies and genotype frequencies. For
a diploid species, each individual inherits two copies of most genes. The Hardy-Weinberg equation
assumes that the alleles for the next generation for any given individual are chosen randomly and
independently of each other. Therefore, we can use the product rule and multiply the sum, p + q,
together. Because p + q = 1, we also know that their product also equals 1:
(p + q)(p + q) = 1
p2 + 2pq + q2 = 1 (Hardy-Weinberg equation)

This equation applies to a gene in a diploid species that is found in only two alleles, which exist at
frequencies designated p and q. As described in the later part of this course, it can be expanded to three
or more alleles.
If this equation is applied to a gene that exists in alleles designated T and t as in our designated pea
plant, then

p2 equals the genotype frequency of TT

2pq equals the genotype frequency of Tt

q2 equals the genotype frequency of tt

If p = 0.8 and q = 0.2 and if the population is in Hardy-Weinberg equilibrium, then

TT = p2 = (0.8)2 = 0.64

Tt = 2pq = 2(0.8)(0.2) = 0.32

tt = q2 = (0.2)2 = 0.04

In other words, if the allele frequency of T is 80% and the allele frequency of t is 20%, the genotype
frequency of TT is 64, Tt is 32%, and tt is 4%.

To illustrate the relationship between allele frequencies and genotypes, we compare the Hardy-
Weinberg equation with the way that gametes combine randomly with each other to produce offspring.
In a population, the frequency of a gamete carrying a particular allele is equal to the allele frequency in
that population. In this example, the frequency of a gamete carrying the T allele (or A allele) equals
0.8.

Mating Table

Combination Freq. Offspring

Frequencies
AA Aa aa
AxA pA2 1
Axa pApa 1
axA papA 1
axa pa2 1
pA2 2 pApa pa 2
These are the Hardy-Weinberg frequencies.

We can use the product rule to determine the frequency of genotypes. For example, the frequency of
producing an TT homozygote is 0.8 x 0.8 = 0.64, or 64%. Likewise, the probability of inheriting both t
alleles is 0.2 X 0.2 = 0.04, or 4%. Heterozygotes can be produced in two different ways. An offspring
could inherit the T allele from its father and t from its mother, or T from its mother and t from its father.
Therefore, the frequency of heterozygotes is pq + pq, which equals 2pq; in our example, this is
2(0.8)(0.2) = 0.32, or 32%.

One useful feature of the Hardy-Weinberg equation is that it allows us to determine the frequency of
heterozygotes for recessive genetic diseases. As an example, let’s consider cystic fibrosis, which
involves a gene that encodes a chloride transporter. Persons afflicted with this disorder have an
irregularity in salt and water balance. One of the symptoms is thick mucus in the lungs that can
contribute to repeated lung infections. In Caucasian populations, the frequency of affected individuals
is approximately 1 in 2,500. Because this is a recessive disorder, affected individuals are homozygotes.
If q represents the allele frequency of the disease causing allele, then

q2 = 1/2,500

q2 = 0.0004

We take the square root to determine q:

q = √0.0004

q = 0.02

If p represents the normal allele,

p=1–q

p = 1 – 0.02 = 0.98

The frequency of heterozygous carriers is

2pq = 2(0.98)(0.02) = 0.0392, or 3.92%

The Hardy Weinberg equation predicts an equilibrium --- unchanging allele and genotype frequencies
from generation to generation --- if certain conditions are met in a population. With regard to the gene
of interest, these conditions are as follows:

1. No new mutations: The gene of interest does not incur any new mutations.

2. No genetic drift: The population is sufficiently large that the frequencies of alleles do not change
from generation to generation merely because of random sampling effects.

3. No migration: Individuals do not travel between different populations.

4. No natural selection: All of the genotypes have the same reproductive success.

5. Random mating: With respect to the gene of interest, the members of the population mate with each
other without regard to their phenotypes and genotypes.

The Hardy-Weinberg equation provides a quantitative relationship between allele and genotype
frequencies in a population. Figure 2 below describes this relationship for different allele frequencies
of g and G. As expected, when the allele frequency of g is very low, the GG genotype predominates;
when the g allele frequency is high, the gg homozygote is most prevalent in the population. When the
allele frequencies of g and G are intermediate in value, the heterozygote predominates.

Fig 2 (From RJ Brooker): The relationship between allele frequencies and genotype frequencies
according to the Hardy-Weinberg equilibrium. This graph assumes that g and G are the only two alleles for
this gene

In reality, no population satisfies the Hardy-Weinberg equilibrium completely. Nevertheless, in large

natural populations with little migration and negligible natural selection, the Hardy-Weinberg
equilibrium may be nearly approximated for certain genes. In addition, the Hardy-Weinberg
equilibrium can be extended to situations in which a single gene exists in three or more alleles.
 H-W Equation with Three or More Alleles

The HW equation can be expanded to include three or more alleles. For example let’s consider a
situation in which a gene that exist as three independent alleles: A1, A2, A3. The allele frequency of A1
is designated by the letter P, A2 = q and A3 = r. Under these circumstances, the HW equation
becomes….. (p + q + r)2 = 1

P2 + q2 +r2 + 2pq + 2pr +2qr = 1; where

P2 = genotype frequency of A1A1; q2 = genotype frequency of A2A2

r2 = genotype frequency of A3A3; 2pq = genotype frequency of A1A2

2pr = genotype frequency of A1A3; 2qr = genotype frequency of A2A3

Now here is the question: The gene that affects human blood type can exist in three alleles. In a
Japanese population, the allele frequencies are

IA = 0.28, IB = 0.17, i = 0.55

Based on these allele frequencies, calculate the different possible genotype frequencies and blood type
frequencies.

Answer:

If we let p represent IA, q = IB, and r = i, then

p2
is the genotype frequency of IAIA, which is the type A blood = (0.28)2 = 0.008

q2 is the genotype frequency of IBIB, which is type B blood = (0.17)2 = 0.03

r2 is the genotype frequency of i, which is the type O blood = (0.55)2 = 0.30

2pq is the genotype frequency of IAIB, which is type AB blood = 2(0.28)(0.17) = 0.09

2pr is the genotype frequency of IAi, which is type A blood = 2(0.28)(0.55) = 0.31

2qr is the genotype frequency of IBi, which is type B blood = 2(0.17)(0.55) = 0.19

Type A = 0.08 + 0.31 = 0.39, or 39%

Type B = 0.03 + 0.19 = 0.22, or 22%

Type O = 0.30, or 30%

Type AB = 0.09, or 9%
FACTORS THAT CHANGE ALLELE AND GENOTYPE FREQUENCIES IN POPULATIONS

Genetic variation in natural populations typically changes over the course of many generations. The
term microevolution describes changes in a population’s gene pool from generation to generation.
Such change is rooted in two related phenomena. First, the introduction of new genetic variation into a
population is one essential aspect of microevolution. As will be examined later in this course, gene
variation can originate by a variety of molecular mechanisms. For example, new alleles of preexisting
genes can arise by random mutations. Such events provide a continuous source of new variation to
populations. However, due to their low rate of occurrence, mutations do not act as a major force in
promoting widespread changes in a population. If mutations were the only type of change occurring in
a population, that population would not evolve at a significant rate because mutations are so rare.

Microevolution also involves the action of evolutionary mechanisms that alter the prevalence of a given
allele or genotype in a population. These mechanisms are random genetic drift, migration, natural
selection, and nonrandom mating. The collective contributions of these evolutionary mechanisms over
the course of many generations have the potential to promote widespread genetic changes in a
population. Here, we look at how these mechanisms may affect the type of genetic variation that
occurs when a gene exists in two or more alleles in a population. These mechanisms may cause a
particular allele to be favored, or they may create a balance where two or more alleles are maintained in
a population.