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PRIMUS: Problems, Resources,

and Issues in Mathematics
Undergraduate Studies
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The Hardy-Weinberg Principle

Shawnee L. McMurran
Published online: 08 Jul 2010.

To cite this article: Shawnee L. McMurran (2010) The Hardy-Weinberg Principle,

PRIMUS: Problems, Resources, and Issues in Mathematics Undergraduate Studies, 20:6,
529-549, DOI: 10.1080/10511970.2010.489544

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 PRIMUS, 20(6): 529–549, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 1051-1970 print / 1935-4053 online
DOI: 10.1080/10511970.2010.489544

The Hardy-Weinberg Principle

Shawnee L. McMurran
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Abstract: This module was initially developed for a course in applications of

mathematics in biology. The objective of this lesson is to investigate how the allele
and genotypic frequencies associated with a particular gene might evolve over
successive generations. The lesson will discuss how the Hardy-Weinberg model
provides a basis for comparison when analyzing the evolution of a population.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of PRIMUS for the following free supplemental resource: Sample Solution.]

Keywords: Modeling, matrix algebra, probability, chi-square testing, data analysis,

population genetics, Hardy-Weinberg principle, evolution, inheritance, genetic drift,
selective mating, genotypic fitness, sickle cell anemia.

1. INTRODUCTION

Using the Hardy-Weinberg principle as a baseline, students will be asked

to investigate scenarios in which various hypotheses of the Hardy-
Weinberg principle are not met. The instructor notes include a class
activity for exploring the phenomenon of genetic drift in small popula-
tions, and the investigation exercises include an analysis of effects of the
sickle cell allele on a population and an inquiry into the effects of
selective mating.

This article is part of a series of articles begun in the Volume 20, Number 2,
February 2010, special issue of this journal, ‘‘Application Activities to Enhance
Learning in the Mathematics-Biology Interface.’’ The publication effort has been
supported by Grant #0309909 from the National Science Foundation which was
awarded to the Department of Mathematical Sciences at the U.S. Military Academy.
Address correspondence to Shawnee L. McMurran, Department of Mathematics,
California State University San Bernadino, 5500 University Parkway, San Bernardino,
CA 92407-2397, USA. E-mail: smcmurra@csusb.edu
 530 McMurran

1.1. Requisite Mathematical and Scientific Background

Students should possess strong algebraic skills, facility with elementary

matrix algebra, and familiarity with probability and elementary statistics.
The largest mathematical challenge for students will be to apply these skills
in a complex problem solving framework.
This lesson presumes no background in science other than a secondary-
level course in biology. The background material includes all necessary
definitions and explanations. Students may find it beneficial (and interesting)
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to read Mendel’s original paper [4] and either of the two short papers, [3] or
[5] on the history of the Hardy-Weinberg Law. For additional reading, the
text An Introduction to Mathematical Biology [1] by Linda Allen, provides a
clearly written and accessible resource.

2. BACKGROUND

2.1. Mendelian Genetics and the Hardy-Weinberg Principle

Genetic traits are passed from one generation to the next as individuals within
a population mate and produce offspring. Population genetics involves the
study of the distribution of these traits over time. Inheritance of a trait
depends on the information contained in the chromosomes that are passed
down from generation to generation. A diploid cell contains exactly two
copies of each chromosome. Most animal cells have a diploid set of chromo-
somes. Human cells, for example, obtain one set of 23 chromosomes from
each parent giving them a total of 46 chromosomes.
Instructions for a characteristic such as eye color, curly hair, or blood
type are contained at specific locations along the chromosomes. The instruc-
tions are referred to as genes and the location of a gene along a chromosome
is called its locus. Each gene gives a unique instruction for some character-
istic. A diploid cell has two genes per locus since there are two sets of
chromosomes. Each gene has different variant forms called alleles. For
example, the gene for hair color can be red, brown, blonde, etc.
In this application we consider a simple one locus, two allele example.
Suppose we have a population consisting of individuals with eye colors of
only blue or brown. While this trait is determined by a single gene, there are
two alleles of this gene: one for blue (b) and one for brown (B). Each
individual has two copies of the gene, one inherited from each parent. An
individual’s eye color depends on the combination of alleles: BB, Bb, or bb.
Let us assume that brown eyes are dominant over blue eyes, as they are in
humans. This means that if an individual inherits at least one B allele, then
that individual will have brown eyes. An individual with brown eyes is
described as having phenotype B. The b allele is referred to as the recessive
 Hardy-Weinberg Principle 531

allele. An individual with phenotype b, that is, a blue-eyed individual, must

have two blue alleles (bb). The three genetic combinations, BB, Bb, and bb,
are called genotypes of the locus. The genotypes BB and bb are referred to as
homozygous and the combination Bb is called heterozygous. In the situation
we have described, genotypes BB and bb are respectively referred to as
homozygous dominant and homozygous recessive.
Given a population with known genotypes, we can use mathematical
models to investigate the question of whether the allele and genotypic
frequencies associated with a particular gene change over successive genera-
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tions. We start with a hypothetical example from Mendel’s garden. Gregor

Mendel, an Augustinian monk, is famous for his 19th century studies on the
principles of inheritance [4]. In his work, Mendel considered certain con-
trasting traits of the common garden pea. One of the seven traits examined by
Mendel was blossom color. In his study, Mendel concluded that red pigmen-
tation was dominant and white was recessive.

2.2. Example

Consider a parent population of peas growing in Mendel’s garden. We will

make the following assumptions on this pea population:

1. Pea blossom color phenotypes are purple and white.

2. Purple blossoms express the dominant allele B; white blossoms express
the recessive allele b.
3. Pollination (mating) is random.
4. All genotypes have equal reproduction and survival rates, i.e., they are
equally fit.
5. There is no pollen contamination from outside sources.
6. There are no mutations.
7. Generations are non-overlapping.

Suppose our population consists of 200 pea plants represented by the

color distribution illustrated in Figure 1. By simply looking at the color
distribution we can determine the percentage of plants with each phenotype.
The darker purple-blossomed peas have phenotype B and the lighter white-
blossomed peas have phenotype b. Thus, 60% of the population has pheno-
type B and 40% has phenotype b.
However, we run into problems when we try to determine what percen-
tage of the peas are heterozygous and what percentage are homozygous.
Although we know from our second assumption that the white peas must
be homozygous recessive, a purple pea may have either genotype BB or Bb.
Visually, we cannot distinguish which of the purple peas are homozygous
dominant and which are heterozygous.
 532 McMurran
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Figure 1. Color distribution for a pea plant population.

Now suppose we are able to run some tests from which we determine
that 20% of the initial population is homozygous dominant, i.e., has genotype
BB. How can we use this information to predict the genotypic and allele
frequencies for not only the parent population, but future populations as well?
The calculation of genotypic frequencies in the parent population is
straightforward. If 20% of the population is genotype BB, and all the white
peas, or 40% of the plants, are genotype bb, then the remaining 40% of the
plants must be genotype Bb.
To calculate allele frequencies, let p1 and q1 respectively denote the
proportions of allele B and allele b in the parent generation. Since this initial
population consists of 200 plants and each carries two alleles, there are 400
alleles in the population’s gene pool for this locus. The 40 plants that are
genotype BB contribute a total of 80 B alleles to the gene pool. Another 40%
of the 200 plants are genotype Bb. They contribute 80 B alleles and 80 b
alleles to the gene pool. The remaining 80 plants with genotype bb contribute
160 b alleles. Therefore, p1 ¼ 160/400 ¼ 40% and q1 ¼ 240/400 ¼ 60%.
Now let’s examine how we can use this information to predict the
proportion of each genotype in the next generation. In flowers, egg cells
reside in ovules which are found in the pistil—the female reproductive part of
a flower. Pollen is produced in the stamen—the male reproductive part of a
flower. The fertilization of an egg cell by a pollen cell may result in a seed.
The probability that a randomly selected pollen cell will contribute a B allele
is 0.4 and the probability that a randomly selected egg will contribute a B
allele is 0.4. Under the assumption of random fertilization, the probability
that a seed will be that of a genotype BB plant is the product of the
 Hardy-Weinberg Principle 533
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Figure 2. Punnett square for pea blossom coloration [7].

probabilities: (0.4)2 ¼ 0.16. Similarly, the probability of genotype bb is given

by (0.6)2 ¼ 0.36. An offspring with the Bb genotype can be obtained in two
ways, as illustrated in Figure 2. The diagram is named after the English
geneticist Reginald C. Punnett who wrote Mendelism in 1905, the first text-
book on Mendel’s theories of genetics [6]. Either the pollen contributes allele
B with probability 0.4 while the egg contributes allele b with probability 0.6,
or vice versa. Thus the probability of genotype Bb is 2(0.4)(0.6) ¼ 0.48.
An alternative approach to examining the probabilities is one in which
we consider all possible mating pairs and the probability of offspring with a
given genotype for each pair. The possible mating pairs are (BB, BB), (BB,
Bb), (BB, bb), (Bb, Bb), (Bb, bb), (bb, bb).
In the initial generation, since mating is random, we have the following
mating pair probabilities.

PðBB; BBÞ ¼ ð0:2Þ2 ¼ 0:04 PðBb; BbÞ ¼ ð0:4Þ2 ¼ 0:16

PðBB; BbÞ ¼ 2ð0:2Þð0:4Þ ¼ 0:16 PðBb; bbÞ ¼ 2ð0:4Þð0:4Þ ¼ 0:32
PðBB; bbÞ ¼ 2ð0:2Þð0:4Þ ¼ 0:16 Pðbb; bbÞ ¼ ð0:4Þ2 ¼ 0:16

All offspring from a (BB, BB) pair will inherit a B allele from each parent,
hence all offspring will be genotype BB. With a (BB, Bb) pair, offspring of
 534 McMurran

genotypes BB and Bb will occur with equal probability since one B allele
will be inherited from the BB parent and a B or b allele will be inherited
from the other parent with equal probability. A (Bb, Bb) pair can have
offspring of any genotype. Each of the homogenous genotypes BB and bb
will occur with probability 25% and heterogenous genotype Bb will occur
with probability 50%. Table 1 summarizes the results for all possible pairs
[1]. The entries in the matrix describing the next generation are obtained
by multiplying the mating pair frequency in a particular row with each of
the corresponding offspring fractions in that same row.
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From the table we can predict genotypic frequencies for the second
generation of peas by summing the frequencies in each genotype column:

pBB ¼ 0:04 þ 0:08 þ 0:04 ¼ 0:16

pBb ¼ 0:08 þ 0:16 þ 0:08 ¼ 0:16 ¼ 0:48; and
pbb ¼ 0:04 þ 0:16 þ 0:16 ¼ 0:36

One common misconception in early genetic studies was that, in time

and in the absence of any counteracting factors, phenotypes with the
dominant gene would outnumber those with the recessive gene. In 1908,
Godfrey H. Hardy, an English mathematician, and Wilhelm Weinberg, a
German physician, independently proposed models of population genetics
that show that the genetic structure of a population will not be affected by
heredity alone [3, 5]. The model showed that in the absence of any driving
evolutionary forces, that both allele and genetic frequencies would quickly
reach equilibrium. The Hardy-Weinberg Principle provides a method for
determining allele and genotypic frequencies from generation to generation
under certain ideal conditions. This principle, stated below, provides a
reference point for determining whether evolution has occurred in a
population.

Table 1. Mating and Offspring Probabilities

Offspring fraction Next generation

Mating pair Mating frequency BB Bb bb BB Bb bb

(BB, BB) 0.04 1 0 0 0.04 0 0

(BB, Bb) 0.16 0.5 0.5 0 0.08 0.08 0
(BB, bb) 0.16 0 1 0 0 0.16 0
(Bb, Bb) 0.16 0.25 0.5 0.25 0.04 0.08 0.04
(Bb, bb) 0.32 0 0.5 0.5 0 0.16 0.16
(bb, bb) 0.16 0 0 1 0 0 0.16
 Hardy-Weinberg Principle 535

The Hardy-Weinberg Principle

Assume that in a parent population, a particular gene has two alleles B and b.
Let p1 and q1 respectively denote the initial proportions of alleles B and b. In
addition, assume the following:

1. Mating is random.
2. Genders are evenly distributed among the three genotypes.
3. All genotypes have equal fitness.
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4. There is neither immigration nor emigration.

5. There are no mutations.
6. Generations are non-overlapping.
7. The population is very large.

Then in every generation the allele frequencies remain constant with

pn ¼ p1 and qn ¼ q1. Moreover, from the second generation onwards, the
genotypic frequencies also remain constant with pBB ¼ (p1)2 pBb ¼ 2(p1)(q1)
and pbb ¼ (q1)2.
In other words, the Hardy-Weinberg Principle tells us that the genotypic
and allele frequencies within a population will reach equilibrium in just one
generation given that the hypotheses of the principle hold. Thus the principle
provides a basis of comparison when studying processes that affect gene
frequencies.
The following proof of the Hardy-Weinberg Principle is adapted from
that given by G.H. Hardy in 1908 [3].

Proof. Suppose that in the parent generation the numbers of pure dominants
(BB), heterozygotes (Bb), and pure recessives (bb) are as a : 2b : , respectively.
Then, we have

aþb bþ
p1 ¼ and q1 ¼ :
a þ 2b þ  a þ 2b þ 

Under the ideal hypotheses proposed by the principle, in the next

generation the probability of each genotype will be given by pBB ¼ (p1)2,
pBb ¼ 2(p1)(q1), and pbb ¼ (q1)2 (See Figure 2). It follows that the numbers of
genotypes BB, Bb, and bb will, respectively, be as (a þ b)2: 2(a þ b) (b þ ):
(b þ )2, or ^ ^ : ^. The probability of allele B in this second generation
a : 2b
will then be

aþb
^ ^ ða þ bÞ2 þ ða þ bÞðb þ Þ
p2 ¼ ¼ :
^ þ ^ ða þ bÞ2 þ 2ða þ bÞðb þ Þ þ ðb þ Þ2
a þ 2b
^
 536 McMurran

This simplifies to

ða þ bÞða þ 2b þ Þ aþb
p2 ¼ 2
¼ ¼ p1 : (1)
ða þ 2b þ Þ a þ 2b þ 

Similarly, the probability of allele b in the second generation, q2, is given by

ðb þ Þða þ 2b þ Þ bþ
q2 ¼ ¼ ¼ q1 : (2)
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ða þ 2b þ Þ2 a þ 2b þ 

By similar arguments we find that p3 ¼ p2 and q3 ¼ q2. It follows from

equations (1) and (2) that p3 ¼ p1 and q3 ¼ q1. Following this chain of
reasoning for each generation we find that pn ¼ p1 and qn ¼ q1 for all n.
Hence, the first conclusion of the Hardy-Weinberg Principle holds.
Using the same argument as that employed for the second generation, we
have that the numbers of third-generation genotypes BB, Bb, bb are as
ð^ ^ 2 : 2ð^
a þ bÞ ^ b
a þ bÞð ^ þ ^Þ : ðb
^ þ ^Þ2 , respectively. However,

ð^ ^ 2 ¼ ½ða þ bÞ2 þ ða þ bÞðb þ Þ2

a þ bÞ
¼ ða þ bÞ2 ða þ 2b þ Þ2 :

Similarly, 2ð^ ^ b
a þ bÞð ^ þ ^Þ ¼ 2ða þ bÞðb þ Þða þ 2b þ Þ2 and
^ þ ^Þ ¼ ðb þ Þ ða þ 2b þ Þ2 . Thus, the ratios of the numbers of geno-
ðb 2 2

types BB, Bb, bb in the third generation simplify to (a þ b)2: 2(a þ b) (b þ ):
(b þ )2. This is the same distribution as that given for the second generation. It
follows that each successive generation will have the same ratios. Therefore, the
second conclusion of the Hardy Weinberg Principle holds.

2.3. Chi-Square Testing

Before presenting the problems for investigation, we should briefly review

some of the statistics used in sample studies. Since it is usually not feasible to
test every member of a large population, sample studies are crucial to
modeling. Suppose we wish to determine if a locus for a certain population
is evolving. One way to do this is to test observed genotypic frequencies
against expected genotypic frequencies using Pearson’s chi-square goodness-
of-fit test.
For example, suppose we have 50 samples of a certain locus. In our
sample we observe 22 individuals with genotype BB, 21 individuals with
genotype Bb, and 7 individuals with genotype bb. Should we accept or reject
the null hypothesis that the population is in Hardy-Weinberg equilibrium?
 Hardy-Weinberg Principle 537

If we compute allele probabilities for the sample we obtain the following:

44 þ 21 21 þ 14
p¼ ¼ 0:65 and q¼ ¼ 0:35:
100 100

Assuming that the population is in Hardy-Weinberg equilibrium, we can

use the allele probabilities and the second conclusion of the Hardy-Weinberg
Principle to compute the expected genotypic probabilities:
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pBB ¼ p2 ¼ 0:4225; pBb ¼ 2 pq ¼ 0:4550; pbb ¼ q2 ¼ 0:1225:

Table 2 provides a summary for the calculation of the corresponding chi-

square value. Each expected value (e) is obtained from the product of the corre-
sponding expected genotypic probability with the number of samples. We obtain a
chi-square value of 5.8554 in a system with two degrees of freedom. This corre-
sponds to a probability of 0.0535, indicating that in a large number of similar tests on
a population that is in Hardy-Weinberg equilibrium, deviations at least as great as
those observed would occur in about 5.35% of those tests by chance alone.
Therefore, there is not sufficient evidence at a 5% level of significance to reject
the claim that the population is in Hardy-Weinberg equilibrium.
Now what if our sample was much larger, yet had the same proportion of
genotypes as that in the smaller sample given above? Suppose, for example,
we have 50,000 samples of which 22,000 individuals have genotype BB,
21,000 individuals have genotype Bb, and 7,000 individuals have genotype
bb. The chi-square calculation for this sample is given in Table 3. The
probability corresponding to a chi-square value of 5855 is approximately 0.

Table 2. Chi-Square Calculation

Genotype Observed Expected (e) Deviation (d) d2/e

BB 22 15.21 6.79 3.0312

Bb 21 16.38 4.62 1.3031
bb 7 4.41 2.59 1.5211
chi-square value: 5.8554

Table 3. Chi-Square Calculation for a Large Sample

Genotype Observed Expected (e) Deviation (d) d2/e

BB 22,000 15,210 6790 3031

Bb 21,000 16,380 4620 1303
bb 7,000 4,410 2590 1521
chi-square value: 5855
 538 McMurran

It would be practically impossible to get deviations this large or larger from a

population in Hardy-Weinberg equilibrium, so we can reject this hypothesis
with a very high level of confidence.

3. PROBLEMS FOR INVESTIGATION

1. Consider the purple and white pea example discussed in the reading. Recall
that in the introductory example we determined that for the second generation
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the probabilities of each genotype were given by pBB ¼ 0.16, pBb ¼ 0.48, and
pbb ¼ 0.36. Assume the hypotheses of the Hardy-Weinberg Principle hold
and that the second generation of pea plants has population size N.

a. Show that the first conclusion of the Hardy-Weinberg Law holds. That
is, show that the allele frequencies in each generation remain constant.
b. Show that the second conclusion of the Hardy-Weinberg Law holds.
That is, show that the genotypic frequencies from the second genera-
tion onward remain constant.

2. Set up a mating and offspring table similar to Table 1 to calculate the

genotypic frequencies of third generation offspring for the purple and white
pea example. (Note that you will have to use mating frequencies calculated
from the genotypic frequencies of the second generation.) Use the results from
the table to confirm that the expected genotypic frequencies for the third
generation are the same as those of the second generation.
3. Suppose we wish to conduct a breeding experiment on the purple and
white pea plants to predict the behavior of the genotype distribution in the
long-term. In one experiment we choose a plant of genotype Bb and a
plant of genotype bb. This particular pair of plants happen to produce 30
seeds of which 10 produce purple blossoms (phenotype B) and 20 produce
white blossoms (phenotype b).

a. What is the distribution of B alleles and b alleles in the seed population?

b. If the population was in Hardy-Weinberg equilibrium, how many of
each type of allele would we expect?
c. Calculate the chi-square value corresponding to the observed allele
frequencies and the expected allele frequencies. Then find the prob-
ability that a sample of this size from a population that is in Hardy-
Weinberg equilibrium would exhibit deviations at least as large as
those observed in this experiment. (Note: The chi-square calculation
for this example involves a system with only one degree of freedom.
One may wish to consider using Yates’ correction for continuity when
calculating the chi-square value.)
 Hardy-Weinberg Principle 539

d. Should this experiment lead us to expect that our pea population is not
in Hardy-Weinberg equilibrium? In other words, should we expect the
population to evolve?

4. If mating is selective, then the genotype equilibrium of the Hardy-Weinberg

principle may not be maintained and the population may evolve. Since the
dynamics of selective mating in nature can be quite complicated, and
involve violations of other Hardy-Weinberg hypotheses, we consider a
hypothetical example. Suppose a large population of fish has recently
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been stocked in a pond. They have only two color phenotypes: yellow
and blue. The yellow fish express the dominant allele B and the blue fish
express the recessive allele b. Strangely enough, the fish prefer to mate with
fish of the opposite color. In fact, a fish will mate with another fish of the
same color only if no opposite color mates are available.
Suppose that the initial population is 36% yellow (phenotype B) and
64% blue (phenotype b). Also, assume that each generation of fish has
equal numbers of male and female fish, that each gender has the same
genotypic distribution, and that each fish has only one mate.

a. Predict what effects selective mating will have on this population.

What do you think will happen in the second generation? What do you
think will happen in the long run? Do you think the population will
evolve or settle down to some sort of equilibrium?
b. Suppose the initial population has a genotypic distribution corresponding
to one in Hardy-Weinberg equilibrium. Show that, in this case, the allele
frequencies are given by p ¼ 0.2 and q ¼ 0.8, and that the genotypic
frequencies are given by pBB ¼ 0.04, pBb ¼ 0.32 and pbb ¼ 0.64.
c. Create a mating and offspring table for the first generation of mating
pairs. How do the predicted allele and genotypic frequencies for the
second generation compare to those of the first generation?
Note: Since 64% of the fish are blue and 36% are yellow, all the
yellow fish will find opposite color mates and we can assume that
72% of the population will be in an opposite color mating pair:
(BB, bb) or (Bb, bb). The remaining blue fish will settle for the
same color mating pair (bb, bb).
d. Create a mating and offspring table for the second generation of
mating pairs. How do the predicted allele and genotypic frequencies
for the third generation compare to those of the second generation?
What does this tell you about the evolution of the population?

5. Suppose that in Problem 4 the initial population is 64% yellow (phenotype

B) and 36% blue (phenotype b). As before, we will assume that the initial
population has a genotypic distribution corresponding to one in Hardy-
Weinberg equilibrium so that pBB ¼ 0.16, pBb ¼ 0.48 and pbb ¼ 0.36.
 540 McMurran

a. Predict what effects selective mating will have on this population.

What do you think will happen in the second generation? What do you
think will happen in the long run?
b. Show that the second generation will have the following (approxi-
mate) genotypic frequencies: pBB ¼ 0.11, pBb ¼ 0.58, pbb ¼ 0.31.
c. Create a mating and offspring table for the second generation of
mating pairs and third generation offspring.
d. Model the genotypic frequencies for 15 generations. What happens in
the long run? Why do you think this is?
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e. What happens to the allele frequency in the long run? Why?

6. Analyze the selective mating problem for the blue and yellow fish intro-
duced in Problem 5 for fish that prefer to mate in same color pairs.
7. Natural selection in nature arises when some genotypes are able to survive
and reproduce at a higher rate than others. In the absence of any other
counteracting factors, genotypes which are more ‘‘fit’’ than others
become more common. The absolute fitness of a genotype is measured
by the ratio of the number of individuals with that genotype after selection
to the number of individuals with that genotype before selection. Relative
fitness compares the average number of surviving progeny of a given
genotype in a generation to the average number of surviving progeny of
competing genotypes in that same generation.
Suppose a rare dominant gene enters a population as a mutation and
that phenotypes with this allele (B) are more fit than those without. Since
B is dominant, phenotypes BB and Bb will have the same fitness. Normal-
ize this value to one. Assume that the frequency of the B allele in the
parent population is a relatively small value, say 0.05.

a. Model the long-term behavior of a large population for which the bb

genotype has a relative fitness of 0.5. Note: To say that genotype bb
has a relative fitness of 0.5 means that bb genotypes reproduce at half
the rate of a genotype with a relative fitness of 1. This behavior can be
modeled by counting only half the alleles from the bb genotype in the
calculation for offspring frequencies in the next generation.
b. Repeat part (a) for bb genotype fitness values of 0.9, 0.95, and 0.99.
c. Repeat part (b), but assume that the B allele is recessive rather than
dominant.

8. Sickle cell anemia is an inherited blood disorder that affects hemoglobin,

a protein found in the red blood cells that help carry oxygen throughout
the body. When the defective hemoglobin molecules give up their oxygen,
they have a tendency to cluster and cause the red blood cells to form into a
sickle shape rather than a normal smooth torus shape. The sickle-shaped
 Hardy-Weinberg Principle 541

blood cells tend to get stuck in narrow blood vessels, blocking the flow of
blood. Sickle cell anemia is most commonly found among people whose
ancestors come from sub-Saharan Africa, India, the Middle East, Medi-
terranean countries, and some regions of South and Central America.
The sickle cell allele is a recessive gene that has various effects on
blood cells. In its homozygous form (bb) it causes sickle cell anemia.
Individuals of this genotype often die before the age of reproduction and
therefore the genotype has a low relative fitness. However, the sickle cell
allele also imparts resistance to malaria in both genotypes bb and Bb.
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Thus, in a region for which malaria is a problem, heterozygotes will have

the highest relative fitness since they will be resistant to malaria, but they
do not suffer from sickle cell anemia.
In a study of a group of the Yoruba people of Ibadan, Nigeria, the
frequency of the sickle cell allele among adults was estimated to be q ¼
0.1232. In a particular sample, 9365 individuals were genotype BB, 2993
were genotype Bb, and 29 were genotype bb [2].

a. Show that there is sufficient evidence to support the claim that the
population is not in Hardy-Weinberg equilibrium.
b. Estimate the relative fitness of genotypes BB and bb if the relative
fitness of genotype Bb is normalized to 1.
c. Use the estimates obtained in part (b) to model the population over the
next 10 generations. What fraction of the population does the model
predict will suffer from sickle cell anemia after 10 generations?
d. Suppose a population in which the sickle cell frequency is 0.1232
migrates to a region in which malaria is not a problem, so the relative
fitness of both BB and Bb genotypes will then be the same. What
fraction of the population does the model predict will suffer from
sickle cell anemia after 10 generations?
e. Suppose a eugenicist suggests a plan to eliminate a rare recessive trait
that causes its genotypes to have a lower relative fitness by preventing
any homozygous recessive individual from procreating. Formulate a
response to this suggestion.

9. This problem is intended for students who have participated in the genetic
drift class activity in Section 5. In small populations, gene frequencies may
change simply by chance. A small population may undergo a phenomenon
referred to as genetic drift in which the population eventually becomes
entirely homozygous dominant or homozygous recessive.

a. Use the data collected in class to create a graph of the genetic

frequencies for each generation.
b. Determine the total number of each allele in the gene pool for each
generation and then graph the result for one of the two alleles. What
 542 McMurran

do you notice? What might this imply about the genetic composition
of the population in the long run?
c. If the population was in Hardy-Weinberg equilibrium, what would be
the expected genotypic frequencies for each generation after the first?
Now consider the frequency of each genotype in the last generation for
the experiment. Perform a chi-square test on this data to determine
whether you should accept or reject the hypothesis that the population
is in Hardy-Weinberg equilibrium.
d. Why is hypothesis 7 of the Hardy-Weinberg Principle necessary?
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10. This problem will ask you to investigate the phenomenon of genetic drift
described in Problem 9. An efficient way to explore the topic of genetic
drift is via the use of a program that can simulate a genetic drift
experiment. An online search for such a program will usually result in
a variety of appropriate applets. At the time of this writing the author
found two nice applets located at [9, Selection 3.2] and [10].
Find a program that will allow you to simulate a genetic drift
experiment in small populations and allows you to change the parameter
for the initial allele frequencies. Investigate the following questions by
performing several simulations for each case.

a. If the initial allele frequencies are both 0.5, what happens in the long
term? Is one outcome more probable than another?
b. If one initial allele frequency is greater than another, how is the long
term behavior affected. Will the allele with the greater initial fre-
quency always ‘‘win’’ in the end?

4. INSTRUCTOR NOTES

4.1. Implementation

This lesson was implemented as one of several modules in a 10-week

course on applications of math in biology. The course had no science
prerequisites.
The mathematics prerequisites for the course included elementary differ-
ential equations and linear algebra; however, a foundation in basic probabil-
ity and matrix algebra would be sufficient for this particular lesson.
Three 90-minute class periods were spent on this module. Prior to the
first lesson, students were assigned the background reading and required to
do a short online quiz. During the first lesson period the reading was
discussed and the genetic drift experiment (provided at the end of these
instructor notes) was performed as a class activity. One should expect the
activity itself to consume about 20–30 minutes of class time.
 Hardy-Weinberg Principle 543

Problem 9 was investigated in class as a group. Problems 1–3 were

assigned as homework. The second and third lessons took place in a compu-
ter lab. Students were assigned to small groups and tasked to investigate
Problems 4–8 and 10. Problem 4 was predominantly instructor-guided during
the beginning of the first lab period and the remainder of the problems were
investigated independently. The instructor assessed group progress and pro-
vided guidance when necessary.
Students were given one week after the second lab period to complete,
compile, and write up their results. Most groups were able to complete the
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investigations and begin their write-ups during the allotted class time. (Note:
This module was introduced early in the course and most students were
inexperienced with both modeling and Excel. This was taken under consid-
eration when allocating lab time for the module.)
In our implementation, students had the opportunity to investigate most of
the problems in class. However, the instructor’s role was minimal during the two
lab periods allocated for the investigation. Part, or all, of the investigation could
easily be assigned as a project to be done out of class. In addition, the problems
have been grouped so that instructors may create shorter assignments by focusing
on fewer investigation areas. A breakdown of topic areas is given below.

 Problems 1–3 deal with populations in Hardy-Weinberg equilibrium.

 Problems 4–6 investigate possible effects of selective mating on a popula-
tion.
 Problems 7 and 8 explore models in which the relative fitness of the
genotypes vary.
 Problems 9 and 10 investigate the phenomenon of genetic drift in small
populations. The class activity is necessary for Problem 9. Problem 10 may
be assigned independently and is not dependent on the activity.

Although most solutions were developed with a calculator and a spread-

sheet, instructors may be interested in the free software packages for popula-
tion genetics research and education developed by Dr. Keith Goodnight. A
nice tool for the investigations is his population-genetic simulation that was
developed to demonstrate the effects of selection, drift, mutation, and migra-
tion on allele and genotypic frequencies in a single-locus, two allele system.
(See [9]).

4.2. Student Challenges

Some students may find the background reading rather abstract and perhaps
somewhat counter-intuitive. The classroom activity on genetic drift proved
invaluable in helping students put the reading in context. The experiment not
only contributed to students’ understanding of the dynamics of genetic
 544 McMurran

interactions, it also led them to consider the consequences of removing one of the
hypotheses of the Hardy-Weinberg Principle. Many of our students commented
that the activity helped them connect the reading to the ‘‘real world’’ and make
sense of the mathematics presented.
Several of the problems for investigation require students to set up
variations of Table 1 for situations in which the Hardy-Weinberg Principle
does not hold. When investigating the consequences of removing one of the
hypotheses of the Principle, it can be quite a challenging task for students to
determine how this change will affect mating and/or offspring frequencies.
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We have found that having students make the calculations by hand for at
least two generations seems to help them understand the relationships.
Problem 5 has students do this in parts (b) and (c).
Another effective tool in working through the probabilities can be the
use of ‘‘imaginary populations’’ with a given number of individuals. This
enables students to first work with a concrete example in order to facilitate
the transition to the general case. For example, in Problem 4(c) students need
to determine mating pair probabilities for a population in which mating is
selective. The first generation of this population has genetic frequencies pBB
¼ 0.04, pBb ¼ 0.32, and pbb ¼ 0.64.
Suppose we had a population with 100 male fish and 100 female fish.
For each gender we have 36 yellow fish of which 4 are genotype BB and 32
are genotype Bb. We also have 64 blue fish of genotype bb. Since there are
more blue fish than yellow fish, each yellow fish will have a blue mate. Thus,
36 blue fish from each gender will have yellow mates. This leaves 28 fish of
each gender without yellow mates. These blue fish will mate among them-
selves forming 28 out of 100 mating pairs. In general, as long as there are
more blue fish than yellow, the probability of a (bb, bb) mating pair will be
p(bb, bb) ¼ pbb - (pBB þ pBb). Among the yellow fish, the 4 BB males will
form 4 (BB, bb) mating pairs and the 4 BB females will form 4 (BB, bb)
mating pairs, for a total of 8 (BB, bb) pairs out of 100 total pairs. In general,
the probability of a (BB, bb) pair will be 2pBB. Similarly, the probability of a
(Bb, bb) pair will be 2pBb.

4.3. Benefits

This lesson helped to provide a variety of insights for students. It demonstrated

the role of mathematics in supporting or refuting scientific hypotheses. For
example, although historically it was a common belief that a dominant trait
should eventually ‘‘dominate’’ over a recessive trait, the mathematics of G.H.
Hardy and Wilhelm Weinberg was able to put this theory to rest. The lesson
also highlighted how generalizations of a theorem can be implemented to
model real world phenomena. The Hardy-Weinberg Principle was provided
as an ideal baseline for population dynamics. When students generalize the
 Hardy-Weinberg Principle 545

theorem by leaving off one of the hypotheses, they can begin to explore the
complicated dynamics of evolution. Finally, the use of chi-square analyses and
the experiment on genetic drift emphasize the importance of sample size in
statistics and the vagaries of small sample statistics.

4.4. Improvements or Alternate Implementations

Whether the problems are investigated in class or assigned as an out of class

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project, we recommend providing students with ‘‘progress checks’’ that may

include numerical answers, sample graphs, and/or partial spreadsheets. In our
implementation, we provided a progress check handout at the beginning of
the second lab period after noticing several common computation and for-
mula errors during the first lab period. The progress check allowed students
to assess their own work and self-correct when necessary, thereby improving
the likelihood that students would draw appropriate conclusions from their
investigations. In the course evaluations, students stated that they found the
progress checks particularly helpful for their learning and that they appre-
ciated the opportunity to find and correct their own mistakes.

5. SUPPLEMENTAL CLASSROOM ACTIVITY: EXPLORING

GENETIC DRIFT

In small populations, gene frequencies may change simply by chance. A

small population may undergo genetic drift in which the population even-
tually becomes entirely homozygous dominant or homozygous recessive.
The classroom provides an ideal opportunity to model genetic drift since
the population is relatively small. A good ‘‘population’’ size to work with
would be somewhere between 10 and 30, or 5–15 individuals of each gender.
Smaller population sizes tend to yield more dramatic results. In larger
classes, the instructor may have students team up in order to keep the
population small.
For this experiment we assume that the population size remains constant
from generation to generation. Thus each mating pair will produce exactly
two offspring.
In the simulation, each student or team is given a ‘‘pet’’ with a certain
genotype and gender. The pets will randomly mate, and each mating pair will
produce two offspring, one male and one female. When necessary, offspring
genotypes will be decided via probability, i.e., coin-flipping. Each team will
choose the offspring with the same gender as the parent pet to be their new
pet for the next generation.
Let us assume an initial population of 16, eight males and eight
females, with p ¼ q ¼ 0.5 for each gender. The instructor should post an
 546 McMurran

Table 4. Example of a Completed Class Chart for the Genetic

Drift Activity with 16 Teams

Genotype

Generation BB Bb bb

1 4 8 4
2 3 8 5
3 3 6 7
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4 1 7 8
5 2 5 9
6 2 6 8
7 1 5 10
8 1 8 7
9 1 7 8
10 0 9 7
: : : :
20 1 2 13

empty chart to record class data. See Table 4 for an example of a com-
pleted class chart.
The instructor might then ask the class to determine how many of each
genotype should be in the parent population if the initial population has a
distribution given by Hardy-Weinberg equilibrium. Those values can then be
entered for the first generation. Each student/team will then be provided an
individual data collection sheet, similar in format to the class data sheet, with
the genotype and gender of their pet indicated on the sheet.
It is helpful to prepare the sheets in two colors, one for each gender. For
example, for an experiment with 16 teams, four sheets should have a parent
of genotype BB and two of these sheets might be blue to represent male pets
and two might be pink to represent female pets. Similarly four sheets, two
blue and two pink, should have a parent of genotype bb. And finally, eight
sheets, four blue and four pink, should have a parent of genotype Bb.
After passing out the sheets, the following simulation ensues:

1. Teams ‘‘randomly’’ find a mate for their pet by pairing up with another
team with a pet of the opposite gender. Random mating might be simu-
lated in a number of ways. If time is an issue, a quick method of forming
pairs might be to assign numbers 1–8 to the female pets and letters A–H to
the male pets. Cards or coins with the numbers and letters can then be
randomly selected in pairs from two piles. An even quicker method would
be to use a program to produce random pairs. Such programs can be found
online [8] or written for a computer algebra system such as Maple or
 Hardy-Weinberg Principle 547

Mathematica. In classrooms where time is less of an issue, teams could

mingle, moving about the room, saying hello to another team, then
moving on until they settle on their mates by some pre-determined rule.
2. Each pair of teams decides who gets the first offspring and who gets the
second. Alternatively, the class may agree to assume that the first off-
spring is female and the second is male.
3. The genotype of each offspring is then determined and marked off on the
corresponding team’s data collection sheet. If both teams have a homo-
zygous genotype as a parent, then the genotype of each offspring is pre-
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determined. For example, if the parent from team F is genotype BB and

the parent from team M is genotype bb, then both offspring must have
genotype Bb. However, if either team has a heterozygous parent, then the
genotype of each offspring should be determined by coin flipping. For
example, suppose team F’s parent is BB, but team M’s parent is Bb. Then
team M will flip a coin in order to determine which gene their pet will

Table 5. Examples of Genetic Drift Data for Two Teams

Genotype

Generation BB Bb bb

1 parent pet
2 p
3 p
4 p
5 p
6 p
7 p
8 p
9 p
10 p

Genotype

Generation BB Bb bb

1 parent pet
2 p
3 p
4 p
5 p
6 p
7 p
8 p
9 p
10 p
 548 McMurran

contribute to each offspring — B for heads and b for tails. Note that team
M must flip the coin twice, once for each offspring. If both teams have
heterozygous parents, then both teams will need to flip coins, and each
team will flip the coin once for each offspring.
4. Each team checks off the genotype of their new pet in the corresponding
row for that generation.
5. Steps 1 through 4 are repeated until the desired number of generations are
filled in on the individual data collection sheets. With 4–8 groups of each
gender, significant drift can usually be observed in 10–15 generations.
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Larger groups may need more generations. The teacher can usually tell
when a sufficient number of generations has elapsed by observing the
class. In particular, it will become apparent when several mating pairs
have mates with the same genotypes.
6. At the conclusion of the experiment, the totals for each genotype in each
generation are compiled on the class data chart. The class data can then be
graphed and analyzed.

Table 5 illustrates two examples of completed individual data collection

sheets for 10 generations. The complete results of a sample experiment are
shown in the solution to Problem 9, which can be found in the sample
solution supplement to this article.

REFERENCES

1. Allen, L. J. S. 2006. An Introduction to Mathematical Biology. Upper

Saddle River, NJ: Prentice Hall. (p. 105)
2. Evolution. 2008. In Encyclopædia Britannica Online. http://search.eb.
com.libproxy.lib.csusb.edu/eb/article-49870. Accessed February 11, 2008.
3. Hardy, G. H. 1908. Mendelian proportions in a mixed population. Science,
New series. 28(706): 49–50.
4. Mendel, G. 1986. Experiments in a monastery garden. (Reprint) American
Zoologist. 26(3): 749–752.
5. Stern, C. 1943. The Hardy-Weinberg Law. Science, New Series. 97(2510):
137–138.
6. Punnett, R. C. 2008. In Encyclopædia Britannica Online. http://search.
eb.com.libproxy.lib.csusb.edu/eb/article-9061918P. Accessed July 4, 2008.
7. Punnet Square. http://en.wikipedia.org/wiki/Image:Punnett_square_
mendel_floweres.svg. Permission granted to copy under the terms of the
GNU Free Documentation License, Version 1.2. Accessed February 10, 2008.
8. Random.org. http://www.random.org/lists/. Accessed September 9, 2008.
9. Rice University. Programs for population genetic and relatedness calcula-
tions, and education in evolution and behavioral ecology. http://
www.gsoftnet.us/GSoft.html. Accessed September 9, 2008.
 Hardy-Weinberg Principle 549

10. University of Connecticut. Genetic Drift. http://darwin.eeb.uconn.edu/

simulations/jdk1.0/drift.html. Accessed September 9, 2008.

BIOGRAPHICAL SKETCH

Shawnee McMurran serves on the mathematics faculty at California State

University, San Bernardino. Her background is in partial differential equa-
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tions. Recent research has focused on history of mathematics, along with

increasing involvement with mathematics education.