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EBOOKS Variation and Population Genetics

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This book describes and analyzes genetic and environmental
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Variation and
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the greater your otype frequencies can be used to determine allele frequen-
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mination. Non-Mendelian genetics can affect the evolution of
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Christopher J. Paradiseis professor of biology and environ-
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A. Malcolm Campbell
Variation and Population
Genetics
Variation and Population
Genetics

Christopher J. Paradise, PhD


A. Malcolm Campbell, PhD
Variation and Population Genetics
Copyright Christopher J. Paradise and A. Malcolm Campbell. 2016.

All rights reserved. No part of this publication may be reproduced, stored


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Abstract
This book describes and analyzes genetic and environmental factors that
cause variation in individuals and populations. Data will be used to evalu-
ate the processes by which variation is generated in organisms and how
variation affects natural selection. Genetic factors include mutation, in-
dependent assortment, crossing over, and recombination. Environmental
factors include gradients and differences in abiotic conditions. Genotype
frequencies can be used to determine allele frequencies and this infor-
mation can be used to determine whether a population is evolving at
a genetic locus. The Hardy-Weinberg equilibrium will be applied as a
null model to make this determination. Non-Mendelian genetics can
affect the evolution of viruses and reassortment in viruses will be used to
illustrate another mechanism that generates variation in organisms and
how this mechanism relates to rapid evolution of viruses and the need
for annual flu vaccines.

Keywords
populations, phenotypes, genotype, traits, natural selection, inheritance,
homozygous, heterozygous, alleles, mutation, independent assortment,
meiosis, recombination, crossing over, environmental gradient, law of
segregation, law of independent assortment, genotype frequencies, allele
frequencies, Hardy-Weinberg equilibrium, Hardy-Weinberg theorem,
genetic drift, gene flow
Contents
Preface...................................................................................................ix
Acknowledgments....................................................................................xi
Introduction.........................................................................................xiii
Chapter 1 Individual Organisms Exhibit Variation Caused
by Genetics and theEnvironment......................................1
Heritable Variation, Mutations and Independent
Assortment.....................................................................1
Variation Caused by the Environment................................8
Chapter 2 Population Genetic Information can be Used
toPredict Evolution.........................................................15
Chapter 3 Annual Flu Vaccines are Needed Because of
Non-Mendelian Genetics.................................................25
Ethical, Legal, and Social Implications:
Some People Refuse the Flu Vaccine for
Themselves and Their Children.....................................30
Conclusion............................................................................................35
Glossary................................................................................................37
Index....................................................................................................39
Preface
This book about variation in populations and population genetics is part
of a thirty book series that collectively surveys all of the major themes
in biology. Rather than just present information as a collection of facts,
the reader is treated more like a scientist, which means the data behind the
major themes are presented. Reading any of the thirty books by P aradise
and Campbell provides readers with biological context and comprehen-
sive perspective so that readers can learn important information from a
single book with the potential to see how the major themes span all size
scales: molecular, cellular, organismal, population and ecologic systems.
The major themes of biology encapsulate the entire discipline: informa-
tion, evolution, cells, homeostasis and emergent properties.
In the twentieth century, biology was taught with a heavy emphasis
on long lists of terms and many specific details. All of these details were
presented in a way that obscured a more comprehensive understanding.
In this book, you will learn about biological variation, population ge-
netics and the Hardy-Weinberg theorem, and some of the supporting
evidence behind our understanding. The historic and more recent experi-
ments and data will be explored. Instead of believing or simply accepting
information, readers of this book will learn about the science behind
variation and population genetics, the way professional scientists do
with experimentation and data analysis. In short, data are put back into
the teaching of biological sciences.
Readers of this book who wish to see the textbook version of this
content can go to www.bio.davidson.edu/icb where the pedagogically-
designed and interactive Integrating Concepts in Biology for introduc-
tory biology college courses or a high school AP Biology course can be
accessed.
Acknowledgments
Publishing this book would not have been possible without the generous
gift of Dr. David Botstein who shared some of his Breakthrough Prize
with co-author AMC. Davids gift allowed us to hire talented artists (Tom
Webster and his staff at Lineworks, Inc.) and copyeditor Laura Loveall.
Thanks go to Kristen Mandava of Mandava Editorial Services for project
management and guidance. In particular, we are indebted to Katie Noble
and Melissa Hayban for their many hours and attention to detail.
Kristen Eshleman, Paul Brantley, Bill Hatfield and Olivia Booker
helped us with technology at Davidson College. We are grateful to ad-
ministrators Tom Ross, Clark Ross, Carol Quillen, Wendy Raymond,
Verna Case, and Barbara Lom who had confidence in us and encouraged
us to persist despite setbacks along the way.
Thanks to my wife Amy Brooks for her constant support during the
development of this textbook, and my daughter Evelyn for her endless
energy. Thanks to Malcolm Campbell for his steadfast resolve and opti-
mism. Without him, this book would not exist. Thanks to collaborator
Laurie Heyer for taking my sometimes half-baked math ideas and turn-
ing them into powerful and elegant Bio-Math Explorations. I learned
a lot from both of them. While the math is largely absent from this
book, our collaboration with her made this a better book. Nancy Stamp
at Binghamton University, and Bill Dunson and Richard Cyr at The
Pennsylvania State University influenced me greatly in how I think as
a scientist and approach my teaching. Finally, I thank my students
in Integrated Concepts in Biology II, who enthusiastically participated
in our experiment to redesign introductory biology, starting with the
text and ending with a new approach to teaching biology.
Introduction
Look around any classroom. How many people in the room look the
same? What is the makeup of the class in terms of hair, eye, or skin color?
What about height? There is some variation in all of these traits. Much
of that variation has a genetic component and all of the variation relates
to information. In this chapter, information at the level of the individual
will be consideredfirst by investigating the causes of variation among
individuals and then by examining how genetic information within in-
dividuals plays out at the population level. Genetic and environmental
changes lead to variation within species.
CHAPTER 1

Individual Organisms
Exhibit Variation
Caused by Genetics and
theEnvironment

This book focuses on information in individual organisms, but readers


should keep in mind that individuals make up populations, which are
typically defined as groups of individuals of the same species living in the
same place at the same time. Within most populations, individuals vary
in any number of phenotypes, or the set of observable characteristics
they possess, resulting from the interaction of genotype (their genetic
composition) with the environment. Only very rarely do two individuals
look exactly alike and that there is often much variation among individu-
als. Variation in this context is the extent to which phenotypes differ from
individual to individual. In most populations, each individual is different.
Consider just two examples: eye color and height; both vary quite a bit in
almost any human population.

Heritable Variation, Mutations and


Independent Assortment
In one of the first scientific studies of variation of characteristics, Sir Francis
Galton examined the relationship between the average height of a couple
and the height of their adult offspring (Figure 1). Galton was a British
scientist, explorer, and inventor. Galton used statistics and mathematics
and the slope of a best-fit line to quantify the influence of parents heights
2 VARIATION AND POPULATION GENETICS

74
y = 0.65x + 23.94
72
height of child (inches)

70

68

66

64

62

60
62 64 66 68 70 72 74
mean height of parents (inches)

Figure 1 Data showing the relationship between height of parents


and offspring. The steeper line indicates a slope of one, and the
shallower line indicates the best-fit line indicated by equation. The
size of the circles is proportional to the number of comparisons. Total
sample size = 928 offspring and 205 sets of parents.
Source: Redrawn with original data from Galton 1889.

on the height of their offspring. Sir Francis Galton invented the concept
of linear regression to help quantify this relationship.
There are many phenotypic traits that vary among humans. Some
obvious ones that can be investigated, besides eye color and height, are
weight, hair color and skin color. Every characteristic has some compo-
nent of heritability; that is, there are one or more genes that control the
phenotype for each individual. Eye color is an inherited trait influenced
by more than one gene. Height is thought to be controlled by multiple
genes, but there is also an environmental component of height, including
factors such as nutrition and stress level during development. Malnutri-
tion or exposure to toxins may negatively affect growth, whereas exposure
to hormones may enhance growth. Galton discovered that the heights of
parents correlate with their offspring, but not perfectly. Galton found that
if the average height of parents was low, a high percentage of offspring
were taller than their parents average height, as indicated by the points
above the dashed line for averages below 67 inches (Figure 1). Likewise,
tall parents tended to have more offspring below their average height.
Individual Organisms Exhibit Variation 3

These two trends yielded a best-fit line that had a slope of 0.65, much
less than 1.0. In addition, he found a high degree of variability around
the average for any set of parents, as indicated by the scattering of points
around the best-fit line. Less variation would lead to more or all points
falling on the best-fit line.
Individuals within populations that vary in characteristics also have
varying degrees of success. To illustrate the importance of variation to his
thesis, Darwin defined natural selection as ...preservation of favour-
able individual differences and variations, and the destruction of those
which are injurious... Although Darwin used variation as a central
concept in his Theory of Evolution by Means of Natural Selection, how
variation among individuals in a population was generated or maintained
was not known in Darwins time. There are several different mechanisms
that produce variation among individuals, and they will be explored them
in this chapter.
As Galton observed, a characteristic may be heritable to some extent
and yet highly variable. Therefore, the genetic code is one source of vari-
ability. Charles Darwin wrote in The Origin of Species that if variations in
phenotypes, however slight, are in any way advantageous to an individual,
those variations tend to increase the ability of the individual to survive and
reproduce. If the phenotype is inherited by offspring, then genes playing
a role in determining that phenotype will spread in the population. Al-
though how inheritance of characteristics worked was not understood in
Darwin or Galtons time, their insights and data were important founda-
tions in the study of how variation among individuals affected evolution.
Much of the variation among individuals in a population is caused
by genetic differences; that is, variation in deoxyribonucleic acid (DNA)
sequences. An example that illustrates this source of variation is a study
of blood pressure in rats (Rattus norvegicus) made by Giuseppe Bianchi
and his colleagues. As in humans, some rats have higher blood pressure
than others. The scientists developed two colonies of rats by breeding rats
that had low blood pressure with each other in one colony, and rats that
had higher blood pressure with each other in the other colony. After 85
generations of doing this, the blood pressures were very similar among
individuals within each colony, but very different between individuals in
different colonies (Figure 2).
4 VARIATION AND POPULATION GENETICS

180

160 = systolic pressure


blood presure (mm Hg 1 s.e.)

= diastolic pressure
140

120

100

80

60

40

20

0
high BP low BP
rat colony

Figure 2 Mean blood pressures for rats in the two colonies, measured
in millimeters of mercury. All high blood pressure rats were
homozygous for the adducin genes (Y and R). Low blood pressure
rats were all homozygous for the F gene only.
Source: Data from Bianchi et al., 1994.

The DNA of several genes was tested to determine whether the rats
were homozygous (possessing two copies of the same version of a gene) or
heterozygous (possessing two different versions of a gene) for these genes.
When Bianchi and colleagues tested twenty rats from each colony, they
found that all rats tested were homozygous for each gene within each strain,
with one exception. The exception was a protein called adducin, which is
composed of two subunits (called and ) whose genes are located on two
different chromosomes. The different versions, or alleles, of each protein
subunit differed by only one amino acid. They named the alleles of the
proteins Y, F, R, and Q, depending on the subunit and the amino acid
that was present at the variable position. For the subunit, the scientists
found that a tyrosine (with the one letter code of Y) substituted for a phe-
nylalanine (F) at position 316. Thus Y stands for the mutated subunit in
the high blood pressure colony and F stands for the normal, wild-type
subunit. For the subunit, an arginine (R) substitutes for glutamine (Q)
at position 529. Thus R stands for the mutated subunit in the high blood
pressure colony and Q stands for the normal, wild-type subunit.
Individual Organisms Exhibit Variation 5

138

136
blood pressure (mm Hg 1 s.e.) 134

132

130

128

126

124

122

120
Q/Q Q/R R/R
type of beta adducin in low blood pressure rats

Figure 3 Mean systolic blood pressures of the three combinations


of two versions of the adducin gene in rats from the low blood
pressure colony. Q and R refer to the amino acid present at position
529 on the protein subunit of adducin. Error bars = 1 standard
error (SE).
Source: Data from Bianchi et al., 1994, in text.

The high blood pressure rats were found to be homozygous for the
and R versions of the adducin genes. The low blood pressure rats
Y

were homozygous for the F adducin gene, and the colony had all three
possible genotypes for the subunit: homozygous R, homozygous Q,
and heterozygous with both R and Q. When Bianchi and his colleagues
compared the blood pressures of these rats, they found that, although
lower than the high blood pressure rats, there were differences among the
three genotypes in the low blood pressure rats (Figure 3).
The scientists crossbred rats from the two colonies. Of course, rats
from the high blood pressure colony were homozygous for both adducin
genes. They chose rats from the low blood pressure colony that were also
homozygous for the Q gene. The resulting offspring in the first genera-
tion were rats heterozygous for both genes; that is, they carried one copy
of Y and R from their high blood pressure parent and one copy of F
and Q from their low blood pressure parent. All the first generation rats
were then crossbred to produce rats of every possible combination of the
6 VARIATION AND POPULATION GENETICS

two versions of the two genes. Blood pressure of these rats was measured
to determine the impact of having any combination of these genes.
The resulting average systolic blood pressures of rats in the second
generation were all in between the systolic blood pressures measured in
rats from the two colonies (the original parental generation). After two
generations of crossbreeding rats from the two colonies, the scientists ob-
tained rats with intermediate blood pressures. However, there were still
some differences. Rats that were homozygous for Y and R, same as rats
from the high blood pressure colony, and rats that were homozygous for
Y and heterozygous QR both still had higher blood pressure than rats
that were FF and either RR or QR. Rats that were heterozygous at
the subunit typically had intermediate blood pressures, as did rats that
were homozygous for F and Q.
This study illustrates several processes that increase variation among
individuals. Bianchi and his colleagues concluded that a point mutation,
a change in a single nucleotide in a DNA sequence, was responsible for
producing the two alleles of the and subunits of adducin. These muta-
tions increased the variation among rats, despite the fact that the scientists
separated them out by selecting for rats that had either high or low blood
pressure in the two colonies. The variation increased because after the
mutations there were two alleles of each gene, leading to two versions of
each adducin subunit. That variation produced several combinations of
the adducin protein.
Generations of inbreeding produced individuals that were mostly ho-
mozygous, at least for all but one of the genes tested. Because the scien-
tists were selecting for individuals with a certain phenotype, individuals
with other phenotypes were subsequently lost from the population because
those rats were removed by the researchers. Eventually most of those alleles
that cause undesirable traits in a population were removed from the popu-
lation. In the case of the adducin gene in the low blood pressure colony,
the heterozygous condition produced rats that had the lowest systolic
blood pressure. Although this outcome may be surprising, it illustrates that
individual variation sometimes produces a phenotype that is selected for.
Rats with high blood pressure have associated health problems, such
as red blood cell and kidney dysfunctions. This led the scientists to con-
clude that slightly harmful mutations had occurred over the generations
Individual Organisms Exhibit Variation 7

of inbreeding. The harmful mutations were able to remain in the popula-


tion because the rats were bred in the laboratory. In nature, these harm-
ful mutations are eliminated by natural selection. Although the scientists
identified the two adducin genes as playing a role in high blood pressure,
there are other genes involved, as must be the case in order to obtain
rats in the second generation of crossbreeding that possessed intermediate
blood pressures. The two alleles of the two subunits of adducin interact
when in different combinations to cause wide variation in high blood
pressure, as indicated by the mean blood pressures of rats in the second
generation of crossbreeding. However, none of these rats has blood pres-
sure as low or high as their grandparents, and that variation is caused
by other genes also controlling blood pressure. After two generations of
crossbreeding, the different alleles of these other genes, from the homo-
zygous grandparents, had been reshuffled independently of the adducin
genes, increasing the variation of responses.
The observation of blood pressure variation and the wide range of
combinations of the two versions of the two adducin genes leads to an-
other conclusion about how variation increases and is maintained in indi-
viduals. Independent assortment, when non-homologous chromosomes
migrate without regard to each other during meiosis, leads to recombi-
nation. Recombination leads to new combinations of genes in offspring
that did not occur in the parents, by independent assortment and cross-
ing over, which occurs when paired chromosomes exchange portions of
their DNA during meiosis.
Bianchi and his colleagues knew that the genes coding for the two
subunits of adducin were located on different chromosomes; so they
could predict that when two heterozygous individuals mated, offspring
of those individuals would exhibit one of nine different combinations of
the two genes (Table 1A).
The heterozygotes were obtained from mating of rats from each col-
ony that were homozygous for different versions of the two genes. A het-
erozygote possesses two alleles for a particular gene, resulting in variation
within an individual. However, if the genes were on the same chromo-
some, the variation of outcomes would be limited (Table 1B). This latter
scenario assumes no crossing over. If there were crossing over, the extent
of variation would also increase.
8 VARIATION AND POPULATION GENETICS

Table 1 Variation of combinations of the two adducin genes. All


parents in the matings are heterozygous for both the adducin subunits
and can contribute one of two alleles for each gene to their offspring.
F and Y are alleles of the subunit, and R and q are alleles of the
subunit. A, Variation when the genes are located on two different
chromosomes, showing independent assortment. B, Variation when
the genes are on the same chromosome, with no crossing over.
A range of alleles
contributed from male parent
F/Q F/R Y/Q Y/R
F/Q FF/QQ FF/QR FY/QQ FY/QR
Range of allelles
F/R FF/QR FF/RR FY/QR FY/RR
contributed from
Y/Q FY/QQ FY/QR YY/QQ YY/QR
female parent
Y/R FY/QR FY/RR YY/QR YY/RR
B range of gene versions
contributed from male parent
F/Q F/Q

Range of allelles F/Q FF/QQ FY/QR


contributed from
female parent Y/R FY/QR YY/RR

Source: C. Paradise.

Variation Caused by the Environment


While genetic mechanisms can increase variation among individuals,
variation might also be caused by the environment. For instance, if ex-
pression of various genes is affected by the environment, variation among
individuals in a population may be affected. The effect of the environ-
ment on individual variation can be examined across an environmen-
tal gradient, the gradual change in an environmental factor from one
place to another. For instance, levels of metal contamination in the soil
surrounding metal ore smelting operations decrease as distance from the
smelter increases. Very few plants live in soils near smelters that have been
operating for many decades. Nicholas Caiazza and James Quinn studied
two species of plants near a smelting operation in eastern Pennsylvania,
slender sandwort (Arenaria patula) and Japanese honeysuckle (Lonicera
japonica). They collected plants from sample sites that varied in their dis-
tance from the smelter, along the pollution gradient. In addition, they
documented the level of metal pollutants at each site where plants were
collected (Figure 4).
Individual Organisms Exhibit Variation 9

8000

zinc concentration in soils (ppm)


7000
= sandwort
6000
= honeysuckle
5000

4000

3000

2000

1000

0
near medium far

15
copper concentration in soils (ppm)

12

0
near medium far
proximity to smelting operation

Figure 4 Contamination in soils surrounding a smelting operation in


Pennsylvania. Sandwort plants were collected at three sites (near,
medium, far) and honeysuckle plants were collected at two sites
(near and far). A, Zinc concentrations in parts per million (ppm).
B, Copper concentrations in parts per million (ppm).
Source: From Caiazza and Quinn, 1980, Table 1.

Caiazza and Quinn counted stomata, the gas exchange pores on


leaves, and hairs on the leaves that they collected from the various
sites over a period of 2 years (Figure 5). They also took seeds from the
plants and grew them under standard conditions in a nearby courtyard;
this procedure would help the researchers determine whether differences
they might find near the smelter were due to the environmental gradient
or genetic differences that had evolved among the various populations.
After a period of time, they collected leaves from these courtyard grown
plants and performed the same analyses (see Figure 5).
10 VARIATION AND POPULATION GENETICS

honeysuckle stomata density honeysuckle hair density


lower leaf stomata density (#/mm2)

upper leaf hair density (#/mm2)


900 3.0
= near
800 = medium 2.5
= far
700 2.0

600 1.5

500 1.0

400 0.5

300 0.0
field 77 field 79 courtyard field 77 field 79 courtyard

sandwort stomata density sandwort hair density


upper leaf stomata density (#/mm2)

220 5

lower leaf hair density (#/mm2)


210 4
200
3
190
2
180

170 1

160 0
field 77 field 79 courtyard field 77 field 79 courtyard

Figure 5 Stomata and hair densities of two plants collected at two


times and grown in controlled conditions in a courtyard. Sandwort
plants from the intermediate site were not grown in the courtyard.
Source: Data from Caiazza & Quinn 1980, Tables 2 and 3.

Both species of plants exhibit variation across the gradient. The sand-
wort shows more consistent variation with distance from the smelter, and
honeysuckle still has variation when plants from different sites are grown
under controlled conditions. However, the variation across years is evi-
dence that some environmental factor affected the density of stomata and
hairs. Caiazza and Quinn speculated that heavy metals in the air affect
plants. Air pollution from the smelter affected the soil conditions, but
air quality varies more from year to year than soil conditions, and this
could have led to annual changes in variation among the sites. There is
also a genetic component, which is more evident with honeysuckle, but
there is also an environmental component that increases variation among
individuals. The number of stomata tends to be lower and hairs are denser
closer to the smelter, and that may be in response to polluted air. The
fewer stomata, the fewer pollutants will enter the plants when they open
for gas exchange. A high density of hairs on leaves may trap pollutants,
acting as a filter. The drawback to these changes is that plants will not be
Individual Organisms Exhibit Variation 11

able to obtain as much carbon dioxide as other plants with more stomata,
but this may still be a phenotype that is advantageous and selected for in
a polluted environment.
In another study, Curtis Lively studied an acorn barnacle (Chthamalus
anisopoma) that has variation in shell shapes along a rocky intertidal habi-
tat off the Gulf of California. Barnacles are non-motile marine animals
that cement themselves to rocks and other substrates in tidal zones, in
order to keep from being washed away by the waves.
Lively knew that a certain type of snail, Acanthina angelica, specialized
on feeding on barnacles. This snail has a special spine on its shell that it
uses to pry open barnacles from the top and gain access to the animal in
its shell. Lively knew from the observations of other naturalists that few
barnacles live near where a snail had a refuge, which the snail uses for
protection from desiccation. At intermediate distances from snail refuges,
barnacles with the bent shell type occur sparsely, but more frequently
than barnacles with the cone shell type. The bent shell type has the
opening of the barnacle on the side rather than at the top like the cone
shell type has. Barnacles emerge from the opening, either on the side or
the top, to filter feed in the water. Far from snail refuges, barnacles with
the cone shell type occur at high density and more frequently than bent-
shell barnacles.
To determine whether the variation in shell type was due to an envi-
ronmental factor that affected the development of barnacle shell shape,
Lively needed to distinguish between correlation and causation; the in-
creased presence of bent-shell barnacles could be correlated with the pres-
ence of snails, or it could be caused by the presence of some other factor.
The scientist set up an exclusion experiment with plots where the bar-
nacles were allowed to develop with the snails present and with the snails
excluded. An exclusion experiment is where one or more species are ex-
cluded from experimental plots or habitats. Barnacles with the bent shell
type developed only in the presence of snails (Figure 6).
He then set up other plots where he placed barnacles of each shell
shape, and half of those plots with the snail predator and other half with-
out, and tracked the survival of barnacles with each shell shape over time.
In the absence of the snail predator, barnacles with either shell type sur-
vived equally well (both about 90% after 5 days) and always with higher
12 VARIATION AND POPULATION GENETICS

= cone
120
= bent

number of barnacles ( 1 s.e.)


100

80

60

40

20

0
snail present snail absent
predator treatment

Figure 6 Number of acorn barnacles (Chthamalus anisopoma) in


plots with and without the snail predator (Acanthina) in the predator
exclusion experiment.
Source: From Lively, 1986, Table 1.

survival than in the presence of the snail predator. However, in the pres-
ence of the snail predator barnacles with the bent shell type had much
higher survival (about 80%) than barnacles with the cone shell type
(about 40%).
The barnacle study demonstrates that a predator can cause develop-
mental changes. The bent shell variety is less common overall than the
cone and never developed in the absence of the predator, but a significant
number of them developed in the presence of the predator. However, the
cone shell phenotype was present in both the presence and absence of the
snail. Even in the presence of the predator, there was a large number of
cone-shaped barnacles, indicating that these individuals either did not re-
ceive the predator cue during development or that they were genetically
incapable of growing into the bent shape. As was the case with honey-
suckle and sandwort, environmental factors can alter the physical ap-
pearance of animals but only within the scope of their genetic potential.
The bent shape may be rare in the absence of the predator because of a
decrease in feeding efficiency, but the benefit of having this shell shape in
the presence of the predator is that it increases the probability of survival.
Careful experimentation with proper controls can determine the
causes and extent of natural variation in populations and how this
Individual Organisms Exhibit Variation 13

variation relates to information in populations. Variation among indi-


viduals can lead to the evolution of populations, just as natural selection
acts to alter the relative abundance of individuals with particular charac-
teristics. This chapter demonstrates that variation among individuals and
information in populations increases through mutation, recombination,
independent assortment, and environmental factors. Those variations can
have implications to survival and reproduction, as was observed with the
barnacles, and may be acted upon by the mechanisms of evolution. In
the next chapter, one of the major mechanisms and concepts that scien-
tists study with regard to variation in populations, the Hardy-Weinberg
theorem, is examined.

Bibliography
Bianchi G, Tripodi G, Casari G, et al.: Two point mutations within the
adducin genes are involved in blood pressure variation, Proc Natl
Acad Sci USA 91(9):39994003, 1994.
Caiazza NA Jr, Quinn JA: Leaf morphology in Arenaria patula and
Lonicera japonica along a pollution gradient, Bull Torrey Bot Club
107(1):918, 1980.
Darwin C: On the origin of species by means of natural selection, 1859,
ZETACRAFT Publishing 2010.
Galton F: Natural inheritance, 1889, MacMillan.
Lively CM: Predator-induced shell dimorphism in the acorn barnacle
Chthamalus anisopoma, Evolution 40(2):232242, 1986.
CHAPTER 2

Population Genetic
Information can be Used
toPredict Evolution

Mendels two laws of inheritance are the law of segregation and the law
of independent assortment. The law of segregation states that paired
chromosomes move to opposite nuclei during formation of gametes, and
the law of independent assortment states that non-homologous chro-
mosomes migrate independently of each other. In Chapter 1 the law
of independent assortment was used to describe how non-homologous
chromosomes migrate without regard to each other during meiosis. This
then affects the variation and genetic information in a population of or-
ganisms. In this chapter, the information content in the genes of a popu-
lation will be examined to determine whether the population is evolving
at a genetic locus.
The MN blood group in humans is determined by two alleles at one
locus on chromosome 4. Expression of the gene leads to production of a
glycoprotein that presents on the surface of red blood cells. These glyco-
proteins are used by the immune system to distinguish self from non-self.
MM individuals present one glycoprotein, NN present another, and MN
individuals present both, so a simple blood test can determine pheno-
type and genotype simultaneously. A team of scientists led by Ian Fon-
tanilla collected data on the MN locus in several populations of humans
in the Philippines. The populations that they selected were distributed
along a north-south gradient and across different islands. They collected
blood from over 500 individuals, each of which was asked to fill out a
questionnaire to assess information on place of birth, ethnic identity,
16 VARIATION AND POPULATION GENETICS

= MM
0.8 = HW MM
= MN
= HW MN
= NN
= HW NN
0.6
frequency

0.4

0.2

0.0
Isabela Panga Manilla Cam Sur Cebu Palawan Butuan Dav Sur
population

Figure 7 Observed and Hardy-Weinberg (HW) genotype frequencies


of the MN genetic locus in Philippine populations.
Source: From Arcellana et al., 2011, Figure 2 and calculated from data in Figures 2 and 3.

and migration of individuals from one region to another. The observed


genotype frequencies are depicted in Figure 7 by the bars labeled MM,
MN and NN. The Hardy-Weinberg expected frequencies, also shown in
Figure7, will be discussed further below. Note that the populations in the
Figure7 are arranged from northernmost to southernmost, left to right.
Two populations, Isabela and Butuan, have high observed frequencies of
the MM genotype, while all other populations tested have heterozygous
MN as the modal genotype. The NN genotype the least frequent geno-
type in all but one population.
Genotype frequencies can be used to determine allele frequencies
in a population. For example, to find the frequency of the M allele in the
Isabela population, use the fact that each of the MM individuals has two
M alleles and each of the heterozygotes has one. Suppose there are 100
individuals in the population. As shown in Figure 7, the frequency of the
MM genotype in Isabela is 0.73, and the frequency of the MN genotype
is 0.12. Then there are 100 0.73 = 73 MM individuals and 100
0.12 = 12 MN individuals, for a total of (73 2) + (12 1) = 158
POPULATION GENETIC INFORMATION CAN PREDICT EVOLUTION 17

M alleles. Because there are 100 2 alleles, the frequency of M alleles is


158/200 = 0.79. You can find the frequency of N in a similar way, count-
ing (15 2) + (12 1) = 42 N alleles out of 200, for a frequency of 0.21.
A different hypothetical population size leads to the same allele fre-
quencies because the population size always cancels out in the allele
frequency calculation. Therefore, the MM genotype frequency, denoted
fMM, and the MN genotype frequency, fMN, can be used rather than
the actual number of MM and MN individuals, to calculate allele fre-
quencies. Calculated this way, the frequency of M alleles (denoted p) is
fMM + fMN/2 = 0.73 + 0.12/2 = 0.79, which is the same result found in
the previous paragraph. Similarly, the frequency of N alleles (denoted q)
is fNN + fMN/2 = 0.15 + 0.12/2 = 0.21. The sum of allele frequencies,
p + q, is always 1, which is a good way to check the calculations.
The allele frequencies for each of the eight populations were deter-
mined by the researchers. The two populations, Isabela and Butuan,
that had high observed frequencies of the MM genotype also have the
highest frequencies of the M allele, at about 0.8. The other six popula-
tions that have high frequencies of MN and low frequencies of NN have
frequencies of the M allele between 0.52 and 0.64, with frequencies of the
N allele between 0.36 and 0.48.
To see if the populations were undergoing evolution at the MN locus,
the investigators determined whether the genotype frequencies had been
staying relatively constant, a concept called Hardy-Weinberg equilibrium.
To understand the Hardy-Weinberg theorem and how it can be applied,
an understanding of genetics and basic probability rules is required.
First, consider how many possible pairings of the three genotypes can
occur in a population. Table 2 shows all the possible pairings that can
occur in a large population, and the percentage of offspring from each
pairing that are predicted to be a given genotype. Note that several of the
pairings are the same, representing males of one genotype mating with
females of another as well as the reverse pairing.
Given the genotype frequencies fMM, fMN and fNN, the multiplication
rule for probabilities can be used to compute the probability of each pos-
sible pairing. Table 3 organizes the same information from Table 2, but
by parental genotype, and lists all the possible pairings that can produce
that genotype and with what probability. Various calculations, explained
18 VARIATION AND POPULATION GENETICS

Table 2 Possible combinations of mating pairs in a population of


organisms where three genotypes exist at one genetic locus with
two alleles. Genotypes of offspring are shown as are the theoretical
percentages of each type.
mating of predicted percentages
parental genotypes of offspring genotypes
MM  MM 100% MM
MM  MN 50% MM 50% MN
MM  NN 100% MN
MN  MM 50% MM 50% MN
MN  MN 25% MM 50% MN 25% NN
MN  NN 50% MN 50% NN
NN  MM 100% MN
NN  MN 50% MN 50% NN
NN  NN 100% NN
Source: C. Paradise.

below, can be used to determine the probability of obtaining a target


genotype, but a simpler formula for the predicted percentages of each
offspring genotype can also be derived. The important point to remember
regarding evolution of populations is that if the predicted proportion of
each offspring genotype is the same as the proportion of each parental
genotype, then the population is said to be in Hardy-Weinberg equilib-
rium and is not evolving.
The concept of Hardy-Weinberg equilibrium is that the genotype fre-
quencies are roughly the same from one generation to the next because
no mechanisms of evolution are acting on the population. Therefore, to
quantify the extent to which a population is in Hardy-Weinberg equilib-
rium, the genotype frequencies of the next generation must be predicted
based on the genotype frequencies of the current generation. Table 3 con-
tains the calculation of the next generation frequencies, using the basic
rules for calculating probabilities.
In particular, the multiplication rule and addition rule for computing
probabilities are used to calculate the values in column 6 of Table 3. The
multiplication rule says that the probability of events A and B both occur-
ring is the probability that A occurs multiplied by the probability that B
occurs, provided that A and B are independent events. The addition rule
says that the probability of event A or event B occurring is the probability
that A occurs plus the probability that B occurs, provided that A and B
POPULATION GENETIC INFORMATION CAN PREDICT EVOLUTION 19

Table 3 Ways to get MM, MN, and NN offspring from matings of


MM, MN and NN parents.
(1) (2) (3) (4) (5) (6)
target matings probability probablity probablity of probability of obtaining
genotype that can that offspring that two this mating, target genotype
of produce will be individuals and this target
offspring target target will be of offspring
offspring offspring parental genotype from
genotype genotype the mating
MM MM  MM 1 fMM  fMM fMM2
MM  MN 1/2 fMM  fMN 1/2  fMM  fMN
MN  MM 1/2 fMN  fMM 1/2  fMM  fMN
MN  MN 1/4 fMN  fMN 1/4 fMN2 fMM2  fMM  fMN  1/4  fMN2

MN MM  MN 1/2 fMM  fMN 1/2 fMM  fMN


MM  NN 1 fMM  fNN fMM  fNN
MN  MM 1/2 fMM  fMN 1/2  fMM  fMN
MN  MN 1/2 fMN  fMN 1/2  fMN2
MN  NN 1/2 fMN  fNN 1/2  fMN  fNN
NN  MM 1 fMM  fNN fMM  fNN fMM  fMN  2 fMM  fNN
NN  MN 1/2 fMN  fNN 1/2  fMN  fNN  1/2  fMN2  fMN  fNN

NN MN  MN 1/4 fMN  fMN 1/4  fMN2


MN  NN 1/2 fMN  fNN 1/2  fMN  fNN
NN  MN 1/2 fMN  fNN 1/2  fMN  fNN
NN  NN 1 fNN  fNN fNN2 1/4  fMN2  fMN  fNN  fNN2

Source: C. Paradise and L. Heyer.

are mutually exclusive events. To find the probability that a particular


mating will produce the target offspring genotype, as shown in column
3, the probability that the mother and father each donate the necessary
alleles is multiplied. For example, the probability that an MM mother
and an MN father will produce an MN offspring is 1 0.5 = 0.5. An
MM mother can only donate an M allele, and the MN father has a 50%
probability of donating an N allele.
The multiplication rule gives the probability of each pairing, as shown
in column 4 of Table 3. For example, the probability that the mother is
MM and the father is MM is fMM fMM = fMM2. The multiplication rule
also gives the probability that a particular mating will occur and that mat-
ing will produce the target offspring genotype. Therefore, to get the values
in column 5, the value in column 4 must be multiplied by the value in
column 3. Finally, the addition rule gives the total probability of each tar-
get offspring genotype, because the matings that can possibly produce the
target genotype are mutually exclusive, that is the occurrence of one event
rules out the occurrence of the other. For example, the probability of the
MM offspring genotype is the probability of the MM genotype from
an MM/MM mating or an MM/MN mating or an MN/MM mating or
an MN/MN mating. The corresponding equation is found in column 6.
20 VARIATION AND POPULATION GENETICS

Any population with equal frequencies of homozygotes (no matter


how many heterozygotes there are) is predicted to produce offspring in the
1:2:1 ratio predicted by Mendel, and once in this ratio, the population is
predicted to stay that way forever. However, 0.25, 0.5, 0.25 is not the only
set of genotype frequencies with this property. Even very skewed genotype
frequencies can be in Hardy-Weinberg equilibrium, such as fMM = 0.04,
fMN = 0.32, and fNN = 0.64.
The formulas in Table 3 for calculating Hardy-Weinberg equilibrium
frequencies are rather complicated, but it turns out that there is an easier
way to calculate the same values using the allele frequencies. Intuitively,
it seems like allele frequencies should tell be very informative about the
next generations genotype frequencies. Recall that allele and genotype
frequencies are related such that p = fMM + fMN/2 and q = fNN + fMN/2.
Use these formulas and algebraic manipulation to calculate p2, 2pq, and
q2. If the proportion of M alleles is p and the proportion of N alleles is
q, then it might be predicted that any randomly selected offspring would
be MM with probability p2, MN with probability 2pq, and NN with
probability q2.
Perhaps amazingly, but consistent with the earlier intuition about al-
lele frequencies, p2 = fMM2 + fMM fMN + fMN2/4, the probability of
MM in the offspring generation from Table 3. Similarly, 2pq = fMM
fMN + 2 fMM fNN + fMN2/2 + fMN fNN, and q2 = fMN2/4 + fMN
fNN + fNN2, the probabilities of MN and NN, respectively, in the offspring
generation. Therefore, once the allele frequencies p and q in a population
are known, the Hardy-Weinberg frequencies are very easy to calculate. In-
terestingly, the Hardy-Weinberg frequencies are given by the terms in the
expansion of (p + q)2 = p2 + 2pq + q2. When p and q are both 0.5, these
frequencies are 0.25, 0.5, and 0.25, but the generalized formula works
for any p and q. Now for any population for which observed genotype
or allele frequencies is known, long-run genotype frequencies, assuming
random mating, a large population, no genetic drift, and no gene flow,
can be predicted. If observed and predicted genotype frequencies do not
match, then one of the assumptions is violated and some mechanism of
evolution is operating on the population. These predictions can thus be
used to identify populations undergoing evolution.
POPULATION GENETIC INFORMATION CAN PREDICT EVOLUTION 21

If a population is not in Hardy-Weinberg equilibrium, as in Isabela


(Figure 7 confirms that observed and HW predicted genotype frequen-
cies are not the same), the conditions of the equilibrium are not being
met and evolution is occurring. We can use the information in the actual
genotype and allele frequencies to determine whether a population is in
Hardy-Weinberg equilibrium. If it is not, we might be able to speculate
on why not. For instance, in a plant population with fewer heterozygotes
than expected, we might predict that selfing of flowers is occurring, or
that heterozygotes are selected against for some reason. In other words, we
can use information to predict evolutionary processes.
Once the conditions are met (i.e., evolutionary mechanisms are no
longer acting on the population) the population eventually comes to
equilibrium, but that any population that is not currently in equilib-
rium either had or has some evolutionary mechanism acting on it. These
mechanisms include natural selection, genetic drift due to small popula-
tion size, gene flow, mutation, or possibly non-random mating. Initial
frequencies may change but converge on a stable equilibrium that does
not change over time when the assumptions of no selection, mutation or
gene flow, large population size, and random mating hold.
Returning to Figure 7, note that it shows the Hardy-Weinberg equi-
librium genotype frequencies for the MN genetic locus in the eight
populations in the Philippines in addition to the observed genotype fre-
quencies. Within a population, if the bars of each genotype, observed and
Hardy-Weinberg predicted, are similar in height (as in Palawan), then the
population is judged to be in Hardy-Weinberg equilibrium.
Several populations appear to be in Hardy-Weinberg equilibrium, in-
cluding Manila, which is a large city with much immigration from other
regions of the Philippines. Even if the observed and equilibrial genotype
frequencies are not exactly equal (as is true even for Manila, Pangasinan,
and Davao del Sur), keep in mind that there are always sampling errors and
random events, such as genetic drift, that can affect natural selection and
genotype frequencies. Theoretical Hardy-Weinberg equilibrium condi-
tions include an infinitely large population, which are never observed
in reality. Small errors will lead to slight differences between observed
and Hardy-Weinberg equilibrium genotype frequencies. You may have
22 VARIATION AND POPULATION GENETICS

correctly concluded that four of the eight populations were in or very


close to Hardy-Weinberg equilibrium and no evolution was occurring.
There appears to be no connection between north-south latitude and
whether a population is in or out of equilibrium. However, isolated popu-
lations and/or populations with very low migration are less likely to be in
equilibrium. For instance, Butuan had the lowest rate of migration and
a large population of indigenous people that have not integrated socially
with people of other regions. Isabela is also composed of a high proportion
of a particular ethnic group and the high migration found for that city
turned out to be migrations from nearby towns all with similar ethnicity.
Those two towns were not close together, yet had similar allele frequen-
cies of M and N alleles, frequencies that were much different from all the
other towns and cities. These two towns also appeared to not be in Hardy-
Weinberg equilibrium, and isolation of small population can cause that
through the process of genetic drift. In addition, non-random mating, in
this case inbreeding, may contribute to lack of equilibrium. If popula-
tions of organisms are well-mixed, with lots of immigration and mating
among individuals, scientists would expect to see broad similarities in
genetic structure. That is not observed in this set of eight populations.
Two other towns also appeared to have genotype frequencies that were
not in Hardy-Weinberg equilibrium. One of them, Camarines Sur, had
the highest migration rate. High migration and consequent mating of
migrants with the local population can cause departures from Hardy-
Weinberg equilibrium through the process of gene flow. For instance,
a high proportion of MM individuals coming into the population
could alter the observed ratio of MM and that predicted under Hardy-
Weinberg for the measured allele frequencies. Cebu also appeared to be
out of Hardy-Weinberg equilibrium, perhaps due to isolation on an is-
land. Palawan is also isolated on an island, but had a migration rate twice
that of Cebu, and here it appears that gene flow is perhaps counteracting
the effect of genetic drift.
Scientists can use the information in observed genotype frequencies
to determine allele frequencies and predicted Hardy-Weinberg genotype
frequencies. Although statistical tests exist to determine the probabil-
ity that a population is in or out of Hardy-Weinberg equilibrium, it is
enough here to simply compare observed and predicted frequencies. The
POPULATION GENETIC INFORMATION CAN PREDICT EVOLUTION 23

point is that the information content in genetic loci can be used, as well
as other information about populations, such as isolation and migration,
to speculate on evolutionary mechanisms that may or may not be acting
on such populations.

Bibliography
Arcellana AES, Guzman RMS, Fontanilla IKC: Distribution of MN blood
group types in local populations in Philippines, J Genet 90:e90e93,
2011. Online only: http://www.ias.ac.in/jgenet/OnlineResources/90/
e90.pdf
Hardy GH: Mendelian proportions in a mixed population, Science 28:
4150, 1908.
Hastings A: Hardy-Weinberg theorem, In: Encyclopedia of life sciences,
2001, Macmillan Publishers Ltd., Nature Publishing Group. Avail-
able online: www.els.net.
Weinberg W: On the demonstration of heredity in man, In: Boyer SH
IV, translator: Papers on human genetics, Englewood Cliffs, NJ, 1963,
Prentice-Hall, pp. 415.
CHAPTER 3

Annual Flu Vaccines are


Needed Because of
Non-Mendelian Genetics

In this chapter, the differences in inheritance and information content of


viruses, from what was discussed in the first two chapters, is explored. The
inheritance pattern of genetic information is predictable most of the time,
but nature can produce surprising outcomes through non-Mendelian ge-
netics. Every year, flu vaccines are offered and most people routinely get
them. But other vaccines that are available are not given on annual basis.
For instance, the tetanus vaccine only needs to be updated once every
10 years. Why is influenza, a lung infection caused by a virus with a ribo-
nucleic acid (RNA) genome, different? Further, why should people even
bother when most people who get the flu seem to recover a few days later?
To answer these questions, understand that some people should get
the vaccine annually, especially those with compromised immune systems
and the elderly. Every year, over 200,000 people in the United States are
infected and about 35,000 die from the flu. In 1918, just a few weeks
before the end of World War I, the entire world suffered from a global
epidemic. The flu pandemic, a world-wide disease epidemic, of 1918
killed more people than the number who died in battle during World War
I. Based on recent estimates, as many as 500 million people were infected
by this particular version of flu (50 million died), which means one out
of three people in the world became infected. Over a 3-month period in
1918, over 21 million people died, including 12.5 million in India and
500,000 in America.
Influenza was first identified as an illness in the 1400s when Italians
thought the disease was influenced by the stars, which is where influenza
26 VARIATION AND POPULATION GENETICS

Figure 8 Electron micrograph of influenza A virus. Pill-shaped


viruses reveal their membrane wrappers studded with small spikes of
viral proteins.
Source: Image from the CDC, public domain.

got its name. The 1918 pandemic was caused by the tiny virus called
influenza A (Figure 8). Like any organism, viruses contain genetic infor-
mation that determines their phenotype. Influenza is a single-stranded
RNA (ssRNA) virus, which means its chromosomes are composed of
only one strand of a RNA molecule. Unlike DNA, single-stranded RNA
(ssRNA) is structurally similar to messenger RNA (mRNA) because it is
composed of only one RNA polymer.
Each individual influenza virus contains eight ssRNA chromosomes,
and the virus encodes only eight proteins. Each protein can differ, as mul-
tiple alleles exist for each gene. Therefore, the right combination of these
eight RNA genes, each with multiple alleles and thus multiple proteins,
is what distinguishes a typical flu season from a pandemic, and the varia-
tions in those combinations, as will be seen, is what requires people to get
a vaccine each year.
The influenza virus reproduces by making new copies of the eight
ssRNA chromosomes and packaging them into groups. Other viral ge-
nomes come in many forms and sizes. Their genomes can be composed
FLU VACCINES NEEDED BECAUSE OF NON-MENDELIAN GENETICS 27

of DNA or RNA, single-stranded or double-stranded, circular or linear.


For instance, the human immunodeficiency virus (HIV), the cause of
acquired immune deficiency syndrome (AIDS) has a genome that is less
than 10,000 bases of ssRNA that encodes nine proteins.
The influenza viruses are wrapped by fragments of the host cells
plasma membrane as viruses stimulate the production of tiny membrane
vesicles. They float in the hosts body until they bump into another cell
to infect or are coughed out. Once outside the body, flu viruses remain
infective in the air for a couple of days or they can survive a couple hours
on an object such as a phone or doorknob.
You can see from the electron micrograph in Figure 8 that influenza
is rounded and has small lollipop-shaped spikes all over its surface. Two
proteins called hemagglutinin and neuraminidase form these spikes that
facilitate infection. Hemagglutinin is the influenza protein that allows the
virus to bind to human lung cells and neuraminidase is the viral protein
that facilitates the formation of new viral particles. Influenza binds to
lung cells using the hemagglutinin spikes to grab proteins on the surface
of lung cells of infected individuals. Neuraminidase is an enzyme that
facilitates the virus budding from infected cells and thus leads to more
infection.
Over time, virologists have numbered the different alleles that encode
hemagglutinin (H) and neuraminidase (N) to help track which version
of influenza is prevalent at any given time or location. The 1918 strain
is called H1N1, and it has been the most aggressive strain to date. So
far, scientists have identified 16 different hemagglutinins and 9 different
neuraminidase alleles. Interestingly, the 20092010 flu was a different
subtype of H1N1, but virologists do not understand why the 1918 virus
was extremely virulent, a pathogen that is harmful when it infects a host,
but the 20092010 virus was highly contagious but not virulent.
Based only on the number of existing 18 hemagglutinins and 11
neuraminidase alleles, 198 different genotypes of influenza are possible.
However, the RNA chromosomes are replicated by RNA polymerase,
which produces more mutations than DNA polymerase, so the number
of influenza alleles will increase with time.
With increased genetic variation, it becomes possible that more ani-
mal species could become susceptible to influenza, in addition to those
28 VARIATION AND POPULATION GENETICS

currently susceptible, such as dogs, ducks, chickens, pigs, whales, horses


and seals. In fact, influenzas ability to infect a wide range of mammals
and birds is precisely why this virus is so dangerous. All known strains of
the influenza A virus have been found in birds, except two strains that are
only found in bats. It turns out that wild birds are the primary reservoir
for all influenza A strains and thus birds are thought to be the source
of influenza in other animals. Infection with certain avian influenza A
strains, including some that have the H5 and H7 hemagglutinin allele,
can cause widespread, severe disease and death among some wild and
domestic birds.
People who raise livestock are in close contact with potential host
species for influenza A. Domestic pigs can be infected with human and
avian influenza viruses, in addition to their own swine influenza viruses.
Because of this, pigs may potentially be infected with influenza viruses
from different species at the same time. It is then possible for the genes
of these viruses to mix and create a new virus. For example, a pig infected
with a human influenza virus and an avian influenza virus at the same
time could have those two viruses produce a new virus that had most of
the genes from the human strain, but a hemagglutinin or neuraminidase
from the bird virus. The resulting virus would very likely be able to infect
humans, but it would have at least one surface protein not previously
seen in humans. Humans would then have little or no immune p rotection
against this new influenza A strain. If this new virus causes illness
and can spread easily, an influenza pandemic can occur.
For this reassortment to occur, two very different genotypes or species
of influenza infecting one animal must be in the same cell. These viruses
can then utilize a very different mode of genetic information transfer to
the next generation. In many organisms, reproduction leads to very simi-
lar offspring. However, with influenza, if two different sets of 8 ssRNA
chromosomes are inside one cell, the next generation can contain as many
as 28 = 256 different ssRNA chromosome combinations and thus pro-
duce a large number of new genotypes and phenotypes very rapidly.
Because influenza has been around a long time, possibly through-
out the evolutionary history of humans, it might be considered by some
that all possible combinations of influenza have infected a human before.
Remember, though, that because humans only live about 80 years and
FLU VACCINES NEEDED BECAUSE OF NON-MENDELIAN GENETICS 29

hundreds of combinations of RNA chromosomes are possible, no one


alive today has been exposed to all possible combinations of influenza
chromosomes. Pandemics occur about every 25 years, which means any
individual human will experience about three in their lifetime, including
the pandemic of H1N1 in 20092010. The population at large includes
people who still have antibodies from their last flu virus infection. People
produce antibodies that bind to hemagglutinin and neuraminidase to
prevent these proteins from functioning normally. Therefore, a typical
flu does not infect everyone, nor does it cause much harm because pre-
existing antibodies minimize the infection. However, if a virus is able to
package just the right set of alleles and infect a human, then humanity
could see another pandemic.
The Centers for Disease Control and Prevention (CDC) characterized
influenza A H1N1, influenza A H3N2, and influenza B viruses in the
early part of the 2015 flu season. These early data help determine the for-
mulation of the vaccine that is produced each yearit will be determined
by the prevalence and possibly virulence of the common strains that are
found at the beginning of a flu season. A typical flu virus is not espe-
cially lethal to healthy individuals. However, young children and older
people have weaker immune systems, and they do not produce sufficient
antibodies to neutralize a new infection. Therefore, senior citizens and
young children are advised to get vaccinated, so their bodies have time to
produce fresh antibodies in advance of the next wave of flu viruses. Un-
fortunately, even though wearing a mask produces only a minimal level
of protection, people do that and continue to repeat the mistakes of the
past by not washing their hands frequently when exposed to influenza.
Touching contaminated doorknobs and telephones are the most common
ways to be exposed to influenza, and failing to wash hands will increase
the probability of a person becoming infected and the infection rate of
the population.
In addition to the 20092010 H1N1 virus, H5N1 avian flu periodi-
cally reemerges. Bird flu was first detected in rural China in 1996 when
a lot of geese began to die. The first human case was observed in 1997 in
Hong Kong where H5N1 killed hundreds of people. However, it could
have been worse. In an effort to contain the virus, governments destroyed
millions of domesticated birds to prevent further spread of H5N1. Given
30 VARIATION AND POPULATION GENETICS

the rapid rate of human travel, it would be easy for this particular virus to
reach every corner of the world in a matter of days. However, just as rapid
is the response of world health organizations, like the CDC.
Science knows more about influenza now than it did in 1918. Mil-
lions of birds have been killed to prevent the spread of H5N1, but thou-
sands of subsistence farmers lost their life savings and their ability to feed
themselves. How does humanity weigh the tradeoffs of two bad out-
comes? Eliminating influenza is impossible, because the virus can hide
in many different animals, including whales, which some people still eat.
Therefore, annual vaccinations for susceptible populations and healthcare
workers are a good preventive measure, and the only solution we have
given the lack of a permanent one. Avian flu is many times more virulent
than the pandemics of H1N1, so a devastating pandemic of an avian flu
could happen.
Viral reproduction provides for the continuity of the species by trans-
mitting genetic information to its progeny. However, the RNA genome is
susceptible to errors, which increases the rate of variation due to imperfect
replication and high rates of recombination. In addition to responding to
a new strain of virus each year, a persons immune system remembers pre-
vious strains as a form of biological memory. Furthermore, physicians use
vaccines to transmit immunological memory to their patients to prevent
serious consequences from new infections. With each new flu season and
each new animal infection, humanity runs the risk of a new combination
of chromosomes resulting in a highly contagious and lethal virus. The
ability to randomly generate a new strain of virus is advantageous to the
virus and is a good example of how genetic information is not always
passed on in a predictable pattern, a wrinkle of complexity within idea of
transmission of information at the organism level.

Ethical, Legal, and Social Implications:


Some People Refuse the Flu Vaccine for
Themselves and Their Children
Each year people are advised by medical professionals to get their flu shot.
But many people, including parents with small children, refuse the vac-
cine for themselves and their children. Why? A Harvard University poll
FLU VACCINES NEEDED BECAUSE OF NON-MENDELIAN GENETICS 31

revealed that 61% of Americans planning to refuse flu vaccine dont think
theyre at risk of a serious case of flu. They argue that the flu is not a life-
threatening disease. It will get a person sick, but the probability of dying
is very low. Yes, people die from the flu they say, but not the average,
healthy individual. Even among the elderly, the risk of death from the flu
is 1 in 1000.
Influenza, however, is not a mild illness; it can make a person very sick
for 3 to 5 days. This takes a toll on student learning, worker productivity,
and the economy. It can also lead to more hospital visits, taking up beds
even in intensive care units. It can be very serious, and in fact hundreds
of Americans do die each year of the flu. Not only can a person help
themselves avoid that fate, they can help reduce the spread of infections to
other individuals, including those that are immunocompromised and are
not able to get an annual vaccine, if the person remains flu-free.
Others argue that the vaccine may not be available until a human
population is in the middle of an epidemic, and then it is too late. How-
ever, it turns out that not everyone gets the flu at the same time. Even in
areas where there is widespread flu, studies suggest that only about 5% to
10% of the population has been infected, and there is the potential for
further infections and lengthening the flu season if a substantial propor-
tion of the population is unvaccinated.
Opponents of the flu vaccine say that it is ineffective. A person may
still get the flu even if they get the vaccine. Some annual flu vaccines have
been particularly ineffective. However, scientists know that just because two
events happen in sequence (a person gets the shot and then he or she gets the
flu) does not mean that one caused the other. The vaccine protects against
the three genotypes of the virus that scientists predict will be most common
or virulent that year. Scientists take an educated guess as to what three of
several hundred genotypes of flu virus they expect will have the greatest
virulence. As mentioned previously, early data collected by the CDC allow
for the guess to be more educated. In early 2015, influenza A H1N1,
influenza A H3N2, and influenza B viruses were the three strains found.
These can be used to develop and ramp up production of a vaccine, which
will be protective against these three strains but not others.
When a person gets the flu vaccine, their body produces antibodies to
those three specific strains. If a fourth strain comes to dominate later in
32 VARIATION AND POPULATION GENETICS

the flu season, the vaccine will be ineffective. Other strains can infect that
person, and there are lots of other non-influenza viruses going around
during flu season. In fact, influenza accounts for less than one-third of
flu-like illnesses during flu season. Because people who are vaccinated do
not get the most virulent flu strain, they actually suffer less flu-like illness
than the people who do not get vaccinated.
Then there are opponents who argue that if a person gets the nasal
spray vaccine they will shed the flu virus and likely infect others. How-
ever, this version of the virus is called live-attenuated virus, and even if it
is true that vaccinated individuals will shed viral particles, attenuation is
a process that takes an infectious agent and alters it so that it becomes
harmless or less virulent. Again, not getting vaccinated at all might in-
crease a persons susceptibility to influenza, and if they get the flu, they
will definitely shed the live virus for many days.
Some people take measures to strengthen their immune systems
against any invading pathogens. For instance, they use Chinese herbs,
elderberry syrup, and vitamin D, claiming that they get sick less intensely
and less frequently than their friends and neighbors. There is some clini-
cal evidence that vitamin D reduces the likelihood of contracting the flu,
but less or no evidence that other such remedies strengthen the immune
system, which is a nebulous concept to begin with.
There are concerns about the long-term health risks of flu vaccines.
These concerns revolve around the inclusion of thimerosal, which is a
mercury-based preservative, and other heavy metals in vaccines. Some
research suggests a link between annual flu shots and development of
Alzheimer disease, for instance. However, it turns out this is not well
supported, and parts of this argument are not even true. For instance,
single-dose units are made without thimerosal, because they are opened
and used only once, negating the potential for contamination. The
live-attenuated version of the vaccine (the nasal spray vaccine) is also a
single-dose unit without thimerosal. No new vaccines approved by the
Food and Drug Administration (FDA) for children contain thimerosal.
Although multi-dose preparations do contain thimerosal, the scientific
research does not support the argument that thimerosal-containing vac-
cines are harmful. In fact, the CDC, the FDA, the National Institutes of
Health (NIH), the National Academy of Sciences Institute of Medicine,
FLU VACCINES NEEDED BECAUSE OF NON-MENDELIAN GENETICS 33

the Advisory Committee on Immunization Practices (ACIP), and the


American Academy of Pediatrics (AAP) have reviewed the published re-
search and found thimerosal to be a safe product to use in vaccines. In
addition, there have been no clinical trials evaluating the effects of the
flu vaccine in the elderly.
As many people recall there was a flu vaccine in 1976 that might
have been related to a rare but devastating neurological syndrome called
Guillain-Barr syndrome (GBS) in as many as one in 100,000 vaccine re-
cipients. Calculate how many individuals that is if 44 million people got
that vaccine. Even though there have been many safety improvements in
flu vaccine production since then, there is lingering fear of annual vac-
cines. In fact, there is much better testing for contaminants, such as the
suspected bacterial contaminant in the 1976 vaccine, and quality control
testing has been enhanced. And not getting vaccinated, even if a person
is healthy and willing to risk getting sick, may facilitate the spread of the
flu, an epidemic, or worsea pandemic.
Finally, many are fearful of the producers of flu vaccines, because
these companies are profit-driven pharmaceutical companies. The logic
is that the pharmaceutical companies just want to make money, and
they do not always have consumers best interests in mind. But in any
capitalist for-profit enterprise, a market-driven approach wins out. If
companies produced bad or ineffective vaccines that made people sick,
they would quickly find their profits drying up. Yes, these companies
are in business to make money, but they will not do that if they create
inferior products.

Bibliography
Aufderheide JJ: 8 damn good reasons not to get the flu shot, Vactruth.com
(website): http://vactruth.com/2013/02/01/8-damn-good-reasons/.
Accessed March 5, 2014.
Bartlett E: Should I get a flu shot? 5 reasons why not, Holistic Squid
(website): http://holisticsquid.com/should-i-get-a-flu-shot/. Accessed
March 5, 2014.
CDC: Seasonal flu (website): http://www.cdc.gov/flu/. Accessed
December 17, 2008.
34 VARIATION AND POPULATION GENETICS

CDC: Seasonal influenza (flu): influenza vaccine safety (website): http://


www.cdc.gov/flu/protect/vaccine/vaccinesafety.htm. Accessed March
5, 2014.
CDC: Seasonal influenza (flu): thimerosal and 20132014 seasonal flu
vaccines (website): http://www.cdc.gov/flu/protect/vaccine/thimerosal
.htm. Accessed March 5, 2014.
DeNoon DJ: 5 reasons some people fear the swine flu vaccine, WebMD:
cold, flu, & cough health center (website): http://www.webmd.com/
cold-and-flu/features/swine-flu-vaccine-fears. Accessed March 5,
2014.
Ingraham JL, Ingraham CA: Introduction to microbiology, Belmont, CA,
1995, Wadsworth Publishing Company, pp. 752.
US Department of Health and Human Services: Pandemic flu: avian
flu (website): http://www.pandemicflu.gov/index.html. Accessed
December, 17 2008.
World Health Organization: H5N1 avian influenza: timeline (website):
http://www.who.int/csr/disease/avian_influenza/timeline.pdf. Accessed
December 17, 2008.
Conclusion
Several broad topics that are all related to how variation among indi-
viduals is generated, maintained, and selected for have been explored.
Variation among individuals within a population is caused by both ge-
netic and environmental changes and represents information within the
population. Variation among individuals that occurs at the genetic level
leads to evolution. Information at the organismal level reveals fundamen-
tal concepts that are observed over and over in biologyno matter what
species are studied. Unfortunately, the flu virus has its own mechanisms
to generate variable genetic information, and its rapid pace of change
requires annual vaccinations.
Glossary
allele frequencies. The proportions of alleles of a gene, or at a genetic locus.
alleles. Different versions of the same gene.
crossing over. When paired chromosomes exchange portions of their DNA dur-
ing meiosis.
environmental gradient. The gradual change in an environmental factor from
one place to another.
epidemic. Widespread occurrence of an infectious disease at a particular time in
a community.
exclusion experiment. An exclusion experiment is where one or more species are
excluded from experimental plots or habitats.
gene flow. Gene flow is the movement and incorporation of alleles from one
population to another.
genetic code. The set of 64 possible codons that code for the twenty common
amino acids and three stop codons.
genetic drift. The loss of alleles by random causes and not natural selection.
genotype. Genotype is the genetic composition that determines an organisms
appearance or behavior.
genotype frequencies. The proportions of genotypes of a gene, or at a genetic
locus in a population.
Hardy-Weinberg theorem. States that allele and genotype frequencies in a popu-
lation will remain constant from generation to generation in the absence of evo-
lutionary mechanisms.
heterozygous. Heterozygous individuals have two different alleles of a gene.
homozygous. Homozygous individuals have two copies of the same allele of a
gene.
independent assortment. Occurs when non-homologous chromosomes miinde-
pendently of each other during meiosis.
influenza. Influenza is a lung infection caused by a virus with an RNA genome.
inheritance. The process of genetic transmission of traits from parents to offspring.
law of independent assortment. States that non-homologous chromosomes mi-
grate independently of each other during meiosis.
law of segregation. States that paired chromosomes move to opposite nuclei
during formation of gametes.
meiosis. The process of partitioning nuclear DNA that produces haploid gametes
from diploid parental eukaryotic cells.
mutation. A change in DNA sequence.
38 GLOSSARY

natural selection. Adaptive mechanism by which evolution takes place and is


often summarized as differential survival and reproduction.
pandemic. Pandemic is a world-wide disease epidemic.
phenotypes. The ways an organism appears or behaves due to its genetic makeup
and environmental influences.
populations. A population is a group of individuals of the same species living in
the same place at the same time
recombination. Occurs when chromosomal segments of DNA exchange pieces as
happens during prophase I.
single-stranded RNA. Single-stranded RNA (ssRNA) is structurally similar to
messenger RNA (mRNA) because it is composed of only one RNA polymer.
traits. A distinct variant of a phenotype.
vaccines. A substance used to stimulate the production of antibodies and provide
immunity against a disease, prepared from the causative agent of a disease, or its
products, and treated to act as an antigen without inducing the disease.
Index
Acanthina angelica, 11 Flu vaccines, 25
Acorn barnacle (Chthamalus concerns about long-term health
anisopoma), 1112 risks of, 32
Acquired immune deficiency refusal of, 3033
syndrome (AIDS), 27 Fontanilla, Ian, 15
Adducin, 4, 6 Food and Drug Administration
Advisory Committee on (FDA), 32
Immunization Practices
(ACIP), 33 Galton, Francis, 12
Air pollution, 10 Gametes, 15
Allele frequencies, 16, 17 Gene flow, 21
Alleles, 4 Genetic code, 3
Alzheimer disease, 32 Genetic drift, 21
American Academy of Pediatrics Genotype, 1
(AAP), 33 Genotype frequencies, 16, 17
Arenaria patula. See Slender Glutamine, 4
sandwort Glycoprotein, 15
Arginine, 4 Guillain-Barr syndrome (GBS), 33
Avian influenza viruses, 28, 30

Barnacle. See Acorn barnacle H1N1, 27, 29


Bianchi, Giuseppe, 37 H5N1, 2930
Bird flu, 29 Hardy-Weinberg (HW) genotype
Blood pressure variations, frequencies, of MN genetic
in rats, 37 locus, 16
Hardy-Weinberg equilibrium, concept
Caiazza, Nicholas, 810 of, 17, 18, 2022
Centers for Disease Control and Hardy-Weinberg theorem, 17
Prevention (CDC), 29, 32 Hemagglutinin, 27
Chthamalus anisopoma. See Acorn Heterozygous, 4
barnacle Homozygous, 4
Crossing over, 7 Human immunodeficiency virus
(HIV), 27
Darwin, Charles, 3
Independent assortment, 7
Environmental gradient, 8 Influenza, 2532
Epidemic, 25 Influenza A H1N1, 29, 31
Evolutionary processes Influenza A H3N2, 29, 31
population genetic information Influenza A virus, 2629
used to predicting, 1523 Influenza B viruses, 29, 31
Exclusion experiment, 11 Inheritance, 3
40 INDEX

Japanese honeysuckle (Lonicera Quinn, James, 810


japonica), 810
Rattus norvegicus, 38
Law of independent assortment, 15 Recombination, 7
Law of segregation, 15 Refusal of vaccines, reasons
Linear regression, 2 for, 3033
Live-attenuated virus, 32 Ribonucleic acid (RNA) genome, 25
Lively, Curtis, 11
Lonicera japonica. See Japanese Single-stranded RNA (ssRNA) virus,
honeysuckle 26, 28
Slender sandwort (Arenaria
Meiosis, 7 patula), 810
Mendels laws of inheritance, 15 Snails, 1112
Messenger RNA (mRNA), 26 Swine influenza viruses, 28
Mutation, 6
Thimerosal, 3233
Nasal spray vaccine, 32 Traits, 2
National Academy of Sciences Tyrosine, 4
Institute of Medicine, 32
National Institutes of Health Vaccines, 25
(NIH), 32 reasons for refusing, 3033
Natural selection, 3 Variation
Neuraminidase, 27 caused by the environment, 813
1918 pandemic, 2526 of characteristics, 1
of combinations of two adducin
Origin of Species, The, (book), 3 genes, 78
genetic differences, 3
Pandemics, 25, 29, 33 and genetic information, 15
Peoples refusing flu vaccines, reasons importance of, 3
for, 3033 leading to evolution of
Phenotypes, 1, 3 populations, 13
Phenylalanine, 4 among rats blood pressure, 37
Population genetic information, used
to predicting evolutionary
processes, 1523
Populations, 1
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