Introduction to Genetics

• Royal Hemophilia and

Romanov DNA

• The Importance of Genetics

The Role of Genetics in Biology

Genetic Variation is the Foundation

of Evolution         

Divisions of Genetics

• A Brief History of Genetics

Prehistory

Early Written Records

The Rise of Modern Genetics

Twentieth-Century Genetics

The Future of Genetics

• Basic Concepts in Genetics

Royal Hemophilia

and Romanov DNA

On August 12, 1904, Tsar Nicholas Romanov II of Russia

wrote in his diary: “A great never-to-be forgotten day when

the mercy of God has visited us so clearly.” That day Alexis,

Nicholas’s first son and heir to the Russian throne, had been

born.

At birth, Alexis was a large and vigorous baby with yellow

curls and blue eyes, but at 6 weeks of age he began

spontaneously hemorrhaging from the navel. The bleeding

persisted for several days and caused great alarm. As he

grew and began to walk, Alexis often stumbled and fell, as

all children do. Even his small scrapes bled profusely, and

minor bruises led to significant internal bleeding. It soon

became clear that Alexis had hemophilia.

Hemophilia results from a genetic deficiency of blood

clotting. When a blood vessel is severed, a complex cascade

of reactions swings into action, eventually producing a protein

called fibrin. Fibrin molecules stick together to form a

clot, which stems the flow of blood. Hemophilia, marked by

slow clotting and excessive bleeding, is the result if any one

of the factors in the clotting cascade is missing or faulty. In

those with hemophilia, life-threatening blood loss can occur

with minor injuries, and spontaneous bleeding into joints

erodes the bone with crippling consequences.

Alexis suffered from classic hemophilia, which is caused

by a defective copy of a gene on the X chromosome. Females

possess two X chromosomes per cell and may be unaffected

carriers of the gene for hemophilia. A carrier has one normal

version and one defective version of the gene; the normal version

produces enough of the clotting factor to prevent hemophilia.

A female exhibits hemophilia only if she inherits two

defective copies of the gene, which is rare. Because males have

a single X chromosome per cell, if they inherit a defective

copy of the gene, they develop hemophilia. Consequently,

hemophilia is more common in males than in females.

Alexis inherited the hemophilia gene from his mother,

Alexandra, who was a carrier. The gene appears to have

originated with Queen Victoria of England (1819–1901),

( FIGURE 1.1). One of her sons, Leopold, had hemophilia

and died at the age of 31 from brain hemorrhage following

a minor fall. At least two of Victoria’s daughters were carriers;

through marriage, they spread the hemophilia gene to

the royal families of Prussia, Spain, and Russia. In all, 10 of

Queen Victoria’s male descendants suffered from hemophilia.

Six female descendants, including her granddaughter

Alexandra (Alexis’s mother), were carriers.

Nicholas and Alexandra constantly worried about

Alexis’s health. Although they prohibited his participation

in sports and other physical activities, cuts and scrapes

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were inevitable, and Alexis experienced a number of severe

bleeding episodes. The royal physicians were helpless during

these crises—they had no treatment that would stop the

bleeding. Gregory Rasputin, a monk and self-proclaimed

“miracle worker,” prayed over Alexis during one bleeding

crisis, after which Alexis made a remarkable recovery.

Rasputin then gained considerable influence over the royal

family.

At this moment in history, the Russian Revolution broke

out. Bolsheviks captured the tsar and his family and held

them captive in the city of Ekaterinburg. On the night of July

16, 1918, a firing squad executed the royal family and their

attendants, including Alexis and his four sisters. Eight days

later, a protsarist army fought its way into Ekaterinburg.

Although army investigators searched vigorously for the bodies

of Nicholas and his family, they found only a few personal

effects and a single finger. The Bolsheviks eventually won the

revolution and instituted the world’s first communist state.

Historians have debated the role that Alexis’s illness may

have played in the Russian Revolution. Some have argued

that the revolution was successful because the tsar and

Alexandra were distracted by their son’s illness and under the

influence of Rasputin. Others point out that many factors

contributed to the overthrow of the tsar. It is probably naive

to attribute the revolution entirely to one sick boy, but it is

clear that a genetic defect, passed down through the royal

family, contributed to the success of the Russian Revolution.

More than 80 years after the tsar and his family were

executed, an article in the Moscow News reported the discovery

of their skeletons outside Ekaterinburg. The remains

had first been located in 1979; however, because of secrecy

surrounding the tsar’s execution, the location of the graves

was not made public until the breakup of the Soviet government

in 1989. The skeletons were eventually recovered and

examined by a team of forensic anthropologists, who concluded

that they were indeed the remains of the tsar and his

wife, three of their five children, and the family doctor,

cook, maid, and footman. The bodies of Alexis and his sister

Anastasia are still missing.

To prove that the skeletons were those of the royal family,

mitochondrial DNA (which is inherited only from the

mother) was extracted from the bones and amplified with a

molecular technique called the polymerase chain reaction

(PCR). DNA samples from the skeletons thought to belong

to Alexandra and the children were compared with DNA

taken from Prince Philip of England, also a direct descendant

of Queen Victoria. Analysis showed that mitochondrial

DNA from Prince Philip was identical with that from these

four skeletons.

DNA from the skeleton presumed to be Tsar Nicholas

was compared with that of two living descendants of the

Romanov line. The samples matched at all but one nucleotide

position: the living relatives possessed a cytosine

(C) residue at this position, whereas some of the skeletal

DNA possessed a thymine (T) residue and some possessed a

C. This difference could be due to normal variation in the

DNA; so experts concluded that the skeleton was almost

certainly that of Tsar Nicholas. The finding remained controversial,

however, until July 1994, when the body of

Nicholas’s younger brother Georgij, who died in 1899, was

exhumed. Mitochondrial DNA from Georgij also contained

both C and T at the controversial position, proving that the

skeleton was indeed that of Tsar Nicholas.

This chapter introduces you to genetics and reviews

some concepts that you may have encountered briefly in a

preceding biology course. We begin by considering the importance

of genetics to each of us, to society at large, and to

students of biology.We then turn to the history of genetics,

how the field as a whole developed. The final part of the

chapter reviews some fundamental terms and principles of

genetics that are used throughout the book.

There has never been a more exciting time to undertake

the study of genetics than now. Genetics is one of the

frontiers of science. Pick up almost any major newspaper or

news magazine and chances are that you will see something

related to genetics: the discovery of cancer-causing genes;

the use of gene therapy to treat diseases; or reports of possible

hereditary influences on intelligence, personality, and

sexual orientation. These findings often have significant

economic and ethical implications, making the study of genetics

relevant, timely, and interesting.

More information about the

history of Nicholas II and other tsars of Russia and about

hemophilia

The Importance of Genetics

Alexis’s hemophilia illustrates the important role that genetics

plays in the life of an individual. A difference in one

gene, of the 35,000 or so genes that each human possesses,

changed Alexis’s life, affected his family, and perhaps even

altered history.We all possess genes that influence our lives.

They affect our height and weight, our hair color and skin

pigmentation. They influence our susceptibility to many

diseases and disorders ( FIGURE 1.2) and even contribute

to our intelligence and personality. Genes are fundamental

to who and what we are.

Although the science of genetics is relatively new, people

have understood the hereditary nature of traits and have

“practiced” genetics for thousands of years. The rise of agriculture

began when humans started to apply genetic principles

to the domestication of plants and animals. Today, the

major crops and animals used in agriculture have undergone

extensive genetic alterations to greatly increase their yields

and provide many desirable traits, such as disease and pest

1.3 The Green Revolution used genetic techniques to develop new

strains of crops that greatly increased world food production during the

1950s and 1960s. (a) Norman Borlaug, a leader in the development of new

strains of wheat that led to the Green Revolution, and a family in Ghana. Borlaug

received the Nobel Peace Prize in 1970. (b) Traditional rice plant (top) and

modern,high-yielding rice plant (bottom). (Part a, UPI/Corbis-Bettman; part b, IRRI.)

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(a) (b)

resistance, special nutritional qualities, and characteristics

that facilitate harvest. The Green Revolution, which expanded

global food production in the 1950s and 1960s, relied

heavily on the application of genetics ( FIGURE 1.3).

Today, genetically engineered corn, soybeans, and other

crops constitute a significant proportion of all the food produced

worldwide.

The pharmaceutical industry is another area where genetics

plays an important role. Numerous drugs and food additives

are synthesized by fungi and bacteria that have been

genetically manipulated to make them efficient producers of

these substances. The biotechnology industry employs molecular

genetic techniques to develop and mass-produce substances

of commercial value. Growth hormone, insulin, and

clotting factor are now produced commercially by genetically

engineered bacteria ( FIGURE 1.4). Techniques of molecular

genetics have also been used to produce bacteria that remove

minerals from ore, break down toxic chemicals, and inhibit

damaging frost formation on crop plants.

Genetics also plays a critical role in medicine. Physicians

recognize that many diseases and disorders have a hereditary

component, including well-known genetic disorders such as

sickle-cell anemia and Huntington disease as well as many

common diseases such as asthma, diabetes, and hypertension.

Advances in molecular genetics have allowed important

insights into the nature of cancer and permitted the development

of many diagnostic tests. Gene therapy—the direct

alteration of genes to treat human diseases—has become a

reality.

Information about

biotechnology, including its history and applications

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Introduction to Genetics 000

The Role of Genetics in Biology

Although an understanding of genetics is important to all

people, it is critical to the student of biology. Genetics provides

one of biology’s unifying principles: all organisms use

nucleic acids for their genetic material and all encode their

genetic information in the same way. Genetics undergirds

the study of many other biological disciplines. Evolution,

for example, is genetic change taking place through time; so

the study of evolution requires an understanding of basic

genetics. Developmental biology relies heavily on genetics:

tissues and organs form through the regulated expression of

genes ( FIGURE 1.5). Even such fields as taxonomy, ecology,

and animal behavior are making increasing use of genetic

methods. The study of almost any field of biology or medicine

is incomplete without a thorough understanding of

genes and genetic methods.

Genetic Variation Is the Foundation of Evolution

Life on Earth exists in a tremendous array of forms and features

that occupy almost every conceivable environment. All

life has a common origin (see Chapter 2); so this diversity

has developed during Earth’s 4-billion-year history. Life is also

characterized by adaptation: many organisms are exquisitely

suited to the environment in which they are found. The history

of life is a chronicle of new forms of life emerging, old

forms disappearing, and existing forms changing.

Life’s diversity and adaptation are a product of evolution,

which is simply genetic change through time. Evolution

is a two-step process: first, genetic variants arise randomly

and, then, the proportion of particular variants increases or

decreases. Genetic variation is therefore the foundation of all

evolutionary change and is ultimately the basis of all life as

we know it. Genetics, the study of genetic variation, is critical

to understanding the past, present, and future of life.

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5

1.4 The biotechnology industry uses molecular

genetic methods to produce substances of economic

value. In the apparatus shown, growth hormone is

produced by genetically engineered bacteria. (James

Holmes/Celltech Ltd./Science Photo Library/Photo Researchers.)

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1.5 The key to development lies in the regulation

of gene expression. This early fruit-fly embryo

illustrates the localized production of proteins from two

genes, ftz (stained gray) and eve (stained brown), which

determine the development of body segments in the

adult f ly. (Peter Lawrence, 1992. The Making of a Fly, Blackwell

Scientific Publications.)

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Divisions of Genetics

Traditionally, the study of genetics has been divided into

three major subdisciplines: transmission genetics, molecular

genetics, and population genetics ( FIGURE 1.6). Also

known as classical genetics, transmission genetics encompasses

the basic principles of genetics and how traits are

passed from one generation to the next. This area addresses

the relation between chromosomes and heredity, the arrangement

of genes on chromosomes, and gene mapping.

Here the focus is on the individual organism—how an individual

organism inherits its genetic makeup and how it

passes its genes to the next generation.

Molecular genetics concerns the chemical nature of the

gene itself: how genetic information is encoded, replicated,

and expressed. It includes the cellular processes of replication,

transcription, and translation—by which genetic information

is transferred from one molecule to another—and gene

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Concepts

Heredity affects many of our physical features as

well as our susceptibility to many diseases and

disorders. Genetics contributes to advances in

agriculture, pharmaceuticals, and medicine and is

fundamental to modern biology. Genetic variation

is the foundation of the diversity of all life.

000 Chapter I

regulation—the processes that control the expression of genetic

information. The focus in molecular genetics is the

gene—its structure, organization, and function.

Population genetics explores the genetic composition of

groups of individual members of the same species (populations)

and how that composition changes over time and

space. Because evolution is genetic change, population genetics

is fundamentally the study of evolution. The focus of population

genetics is the group of genes found in a population.

It is convenient and traditional to divide the study of

genetics into these three groups, but we should recognize

that the fields overlap and that each major subdivision can

be further divided into a number of more specialized fields,

such as chromosomal genetics, biochemical genetics, quantitative

genetics, and so forth. Genetics can alternatively be

subdivided by organism (fruit fly, corn, or bacterial genetics),

and each of these organisms can be studied at the level

of transmission, molecular, and population genetics.

Modern genetics is an extremely broad field, encompassing

many interrelated subdisciplines and specializations.

Information about careers in

genetics

A Brief History of Genetics

Although the science of genetics is young—almost entirely

a product of the past 100 years—people have been using

genetic principles for thousands of years.

Prehistory

The first evidence that humans understood and applied

the principles of heredity is found in the domestication of

plants and animals, which began between approximately

10,000 and 12,000 years ago. Early nomadic people depended

on hunting and gathering for subsistence but, as

human populations grew, the availability of wild food resources

declined. This decline created pressure to develop

new sources of food; so people began to manipulate wild

plants and animals, giving rise to early agriculture and the

first fixed settlements.

Initially, people simply selected and cultivated wild

plants and animals that had desirable traits. Archeological

evidence of the speed and direction of the domestication

process demonstrates that people quickly learned a simple

but crucial rule of heredity: like breeds like. By selecting

and breeding individual plants or animals with desirable

traits, they could produce these same traits in future

generations.

The world’s first agriculture is thought to have developed

in the Middle East, in what is now Turkey, Iraq, Iran,

Syria, Jordan, and Israel, where domesticated plants and

animals were major dietary components of many populations

by 10,000 years ago. The first domesticated organisms

included wheat, peas, lentils, barley, dogs, goats, and

sheep. Selective breeding produced woollier and more

manageable goats and sheep and seeds of cereal plants that

were larger and easier to harvest. By 4000 years ago, sophisticated

genetic techniques were already in use in the

Middle East. Assyrians and Babylonians developed several

hundred varieties of date palms that differed in fruit size,

color, taste, and time of ripening. An Assyrian bas-relief

from 2880 years ago depicts the use of artificial fertilization

to control crosses between date palms ( FIGURE 1.7).

Other crops and domesticated animals were developed by

cultures in Asia, Africa, and the Americas in the same

period.

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Transmission

genetics

Molecular

genetics

Population

genetics

(c) (d)

(e)

1.6 Genetics can be subdivided into three interrelated

fields. (Top left, Alan Carey/Photo Researchers; top

right, MONA file M0214602 tif; bottom, J. Alcock/Visuals

Unlimited.)

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Concepts

The three major divisions of genetics are

transmission genetics, molecular genetics, and

population genetics. Transmission genetics

examines the principles of heredity; molecular

genetics deals with the gene and the cellular

processes by which genetic information is

transferred and expressed; population genetics

concerns the genetic composition of groups of

organisms and how that composition changes over

time and space.

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Introduction to Genetics 000

Early Written Records

Ancient writings demonstrate that early humans were aware

of their own heredity. Hindu sacred writings dating to 2000

years ago attribute many traits to the father and suggest that

differences between siblings can be accounted for by effects

from the mother. These same writings advise that one

should avoid potential spouses having undesirable traits

that might be passed on to one’s children. The Talmud, the

Jewish book of religious laws based on oral traditions dating

back thousands of years, presents an uncannily accurate

understanding of the inheritance of hemophilia. It directs

that, if a woman bears two sons who die of bleeding after

circumcision, any additional sons that she bears should not

be circumcised; nor should the sons of her sisters be circumcised,

although the sons of her brothers should. This

advice accurately depicts the X-linked pattern of inheritance

of hemophilia (discussed further in Chapter 6).

The ancient Greeks gave careful consideration to

human reproduction and heredity. The Greek physician

Alcmaeon (circa 520 B.C.) conducted dissections of animals

and proposed that the brain was not only the principle site

of perception, but also the origin of semen. This proposal

sparked a long philosophical debate about where semen

was produced and its role in heredity. The debate culminated

in the concept of pangenesis, which proposed that

specific particles, later called gemmules, carry information

from various parts of the body to the reproductive organs,

from where they are passed to the embryo at the moment

of conception ( FIGURE 1.8a). Although incorrect, the

concept of pangenesis was highly influential and persisted

until the late 1800s.

Pangenesis led the ancient Greeks to propose the notion

of the inheritance of acquired characteristics, in which

traits acquired during one’s lifetime become incorporated

into one’s hereditary information and are passed on to

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Concepts

Humans first applied genetics to the domestication

of plants and animals between approximately

10,000 and 12,000 years ago. This domestication

led to the development of agriculture and fixed

human settlements.

1.7 Ancient peoples practiced genetic

techniques in agriculture. (Top) Comparison of

ancient (left) and modern (right) wheat. (Bottom)

Assyrian bas-relief sculpture showing artificial

pollination of date palms at the time of King

Assurnasirpalli II, who reigned from 883–859 B.C.

(Top left and right, IRRI; bottom, Metropolitan Museum of Art,

gift of John D. Rockefeller Jr., 1932.

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000 Chapter I

offspring; for example, people who developed musical ability

through diligent study would produce children who are

innately endowed with musical ability. The notion of the

inheritance of acquired characteristics also is no longer

accepted, but it remained popular through the twentieth

century.

The Greek philosopher Aristotle (384 – 322 B.C.) was

keenly interested in heredity. He rejected the concepts of

both pangenesis and the inheritance of acquired characteristics,

pointing out that people sometimes resemble past

ancestors more than their parents and that acquired characteristics

such as mutilated body parts are not passed on.

Aristotle believed that both males and females made contributions

to the offspring and that there was a struggle of

sorts between male and female contributions.

Although the ancient Romans contributed little to the

understanding of human heredity, they successfully developed

a number of techniques for animal and plant breeding;

the techniques were based on trial and error rather

than any general concept of heredity. Little new was added

to the understanding of genetics in the next 1000 years.

The ancient ideas of pangenesis and the inheritance of acquired

characteristics, along with techniques of plant and

animal breeding, persisted until the rise of modern science

in the seventeenth and eighteenth centuries.

The Rise of Modern Genetics

Dutch spectacle makers began to put together simple microscopes

in the late 1500s, enabling Robert Hooke (1653–1703)

to discover cells in 1665. Microscopes provided naturalists

with new and exciting vistas on life, and perhaps it was excessive

enthusiasm for this new world of the very small that gave

rise to the idea of preformationism. According to preformationism,

inside the egg or sperm existed a tiny miniature

adult, a homunculus, which simply enlarged during development.

Ovists argued that the homunculus resided in the

egg, whereas spermists insisted that it was in the sperm

( FIGURE 1.9). Preformationism meant that all traits would

be inherited from only one parent—from the father if the

homunculus was in the sperm or from the mother if it was in

the egg. Although many observations suggested that offspring

possess a mixture of traits from both parents, preformationism

remained a popular concept throughout much of the

seventeenth and eighteenth centuries.

Another early notion of heredity was blending inheritance,

which proposed that offspring are a blend, or mixture,

◗

1 According to the pangenesis

concept, genetic information

from different parts of the body…

1 According to the germ-plasm

theory, germ-line tissue in

the reproductive organs…

3 …where it is transferred

to the gametes.

2 …travels to the

reproductive organs…

2 …contains a complete set

of genetic information…

3 …that is transferred

directly to the gametes.

(a) Pangenesis concept

Sperm

Egg Egg

Sperm

Zygote Zygote

(b) Germ–plasm theory

1.8 Pangenesis, an early concept of inheritance, compared with

the modern germ-plasm theory.

◗

Introduction to Genetics 000

In June 2000, scientists from the

Human Genome Project and Celera

Genomics stood at a podium with

former President Bill Clinton to

announce a stunning achievement—

they had successfully constructed a

sequence of the entire huan genome.

Soon this process of identifying and

sequencing each and every human

gene became characterized as

"mapping the human genome". As

with maps of the physical world, the

map of the human genome provides a

picture of locations, terrains, and

structures. But, like explorers,

scientists must continue to decipher

what each location on the map can tell

us about diseases, human health, and

biology. The map accelerates this

process, as it allows researchers to

identify key structural dimensions of

the gene they are exploring, and

reminds them where they have been

and where they have yet to explore.

What does the map of the human

genome depict? when researchers

discuss the sequencing of the genome,

they are describing the identification

of the patterns and order of the 3

billion human DNA base pairs. While

this provides valuable information

about overall structure and the

evolution of humans in relation to

other organisms, researchers really

wanted the key information encoded

in just 2% of this enormous map—the

information that makes most of the

proteins that compose you and me.

Comprised of DNA, genes are the

basic units of heredity; they hold all of

the information required to make the

proteins that regulate most life

functions, from digesting food to

battling diseases. Proteins stand as the

link between genes and

pharmaceutical drug development,

they show which genes are being

expressed at any given moment, and

provide information about gene

function.

Knowing our genes will lead to

greater understanding and radically

improved treatment of many diseases.

However, sequencing the entire human

genome, in conjunction with

sequencing of various nonhuman

genomes under the same project, has

raised fundamental questions about

what it means to be human. After all,

fruit flies possess about one-third the

number of genes as humans, and an

ear of corn has approximately the

same number of genes as a human! In

addition, the overall DNA sequence of

a chimpanzee is about 99% the same

as the human genome sequence. As

the genomes of other species become

available, the similarities to the human

genome in both structure and

sequence pattern will continue to be

identified. At a basic level, the

discovery of so many commonalities

and links and ancestral trees with

other species adds credence to

principles of evolution and Darwinism.

Some of the most anticipated

developments and potential benefits of

the Human Genome Project directly

affect human health; researchers,

practicing physicians, and the general

public eagerly await the development

of targeted pharmaceutical agents and

more specific diagnostic tests.

Pharmacogenomics is at the

intersection of genetics and

pharmacology; it is the study of how

one's genetic makeup will affect his or

her response to various drugs. In the

future, medicine will potentially be

safer, cheaper, and more disease

specific, all while causing fewer side

effects and acting more effectively, the

first time around.

There are however some hard

ethical questions that follow in the

wake of new genetic knowledge.

Patients will have to undergo genetic

testing in order to match drugs to

their genetic makeup. Who will have

access to these result—just the health

care practitioner, or the patient's

insurance company, employer/school,

and/or family members? While the

tests were administered for one case,

will the information derived from them

be used for other purposes, such as

for identification of other

conditions/future diseases, or even in

research studies?

How should researchers conduct

studies in pharmacogenomics? Often

they need to group study subjects by

some kind of identifiabe traits that

they believe will assist in separating

groups of drugs, and in turn they

separate people into populations. The

order of almost all of the DNA base

pairs (99.9%) is exactly the same in all

humans. So, this leaves a small

window of difference. There is

potential for stigmatization of

individuals and groups, of people

based on race and ethnicity inherent in

genomic research and analysis. As

scientists continue drug development,

they must be careful to not further

such ideas, especially as studies of

nuclear DNA indicate that there is

often more genetic variation within

"races" or cultures, than between

"races" or cultures. Stigmatization or

discrimination can occur through

genetic testing and human subjects

research on populations.

These are just a few of the

ethical issues arising out of one

development of the Human Genome

Project. The potential applications of

genome research are staggering, and

the mapping is just the beginning.

Realizing this was simply a starting

point, the draft sequences of the

human genome released in February

2001 by the publicly funded Human

Genome Project and the private

company, Celera Genomics, are freely

available on the Internet. A long road

lies ahead, where scientists will be

charged with exploring and

understanding the functions of and

relationships between genes and

proteins. With such exploration

comes a responsibility to

acknowledge and address the ethical,

legal, and social implications of this

exciting research.

The New Genetics

ETHICS • SCIENCE • TECHNOLOGY

by Arthur L. Caplan and Kelly

A. Carroll

Mapping the Human Genome—

Where does it lead, and what does

it mean?

000 Chapter I

of parental traits. This idea suggested that the genetic material

itself blends, much as blue and yellow pigments blend to

make green paint. Once blended, genetic differences could

not be separated out in future generations, just as green paint

cannot be separated out into blue and yellow pigments. Some

traits do appear to exhibit blending inheritance; however, we

realize today that individual genes do not blend.

Nehemiah Grew (1641–1712) reported that plants reproduce

sexually by using pollen from the male sex cells.

With this information, a number of botanists began to experiment

with crossing plants and creating hybrids.

Foremost among these early plant breeders was Joseph

Gottleib Kölreuter (1733–1806), who carried out numerous

crosses and studied pollen under the microscope. He

observed that many hybrids were intermediate between the

parental varieties. Because he crossed plants that differed in

many traits, Kölreuter was unable to discern any general

pattern of inheritance. In spite of this limitation, Kölreuter’s

work set the foundation for the modern study of genetics.

Subsequent to his work, a number of other botanists began

to experiment with hybridization, including Gregor Mendel

(1822–1884) ( FIGURE 1.10), who went on to discover the

basic principles of heredity. Mendel’s conclusions, which

were unappreciated for 45 years, laid the foundation for our

modern understanding of heredity, and he is generally recognized

today as the father of genetics.

Developments in cytology (the study of cells) in the

1800s had a strong influence on genetics. Robert Brown

(1773–1858) described the cell nucleus in 1833. Building on

the work of others, Matthis Jacob Schleiden (1804–1881)

and Theodor Schwann (1810–1882) proposed the concept

of the cell theory in 1839. According to this theory, all life is

composed of cells, cells arise only from preexisting cells, and

the cell is the fundamental unit of structure and function in

living organisms. Biologists began to examine cells to see

how traits were transmitted in the course of cell division.

Charles Darwin (1809–1882), one of the most influential

biologists of the nineteenth century, put forth the theory

of evolution through natural selection and published

his ideas in On the Origin of Species in 1856. Darwin recognized

that heredity was fundamental to evolution, and he

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1.9 Preformationism was a popular idea of

inheritance in the seventeenth and eighteenth

centuries. Shown here is a drawing of a homunculus

inside a sperm. (Science VU/Visuals Unlimited.)

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1.10 Gregor Mendel was the founder of modern

genetics. Mendel first discovered the principles of

heredity by crossing different varieties of pea plants

and analyzing the pattern of transmission of traits in

subsequent generations. (Hulton/Archive by Getty Images.)

◗

Introduction to Genetics 000

conducted extensive genetic crosses with pigeons and other

organisms. However, he never understood the nature of

inheritance, and this lack of understanding was a major

omission in his theory of evolution.

In the last half of the nineteenth century, the invention

of the microtome (for cutting thin sections of tissue for

microscopic examination) and the development of improved

histological stains stimulated a flurry of cytological research.

Several cytologists demonstrated that the nucleus had a role

in fertilization. Walter Flemming (1843–1905) observed the

division of chromosomes in 1879 and published a superb

description of mitosis. By 1885, it was generally recognized

that the nucleus contained the hereditary information.

Near the close of the nineteenth century, August

Weismann (1834–1914) finally laid to rest the notion of the

inheritance of acquired characteristics. He cut off the tails

of mice for 22 consecutive generations and showed that the

tail length in descendants remained stubbornly long.

Weismann proposed the germ-plasm theory, which holds

that the cells in the reproductive organs carry a complete

set of genetic information that is passed to the gametes

(see Figure 1.8b).

Twentieth-Century Genetics

The year 1900 was a watershed in the history of genetics.

Gregor Mendel’s pivotal 1866 publication on experiments

with pea plants, which revealed the principles of heredity,

was “rediscovered,” as discussed in more detail in Chapter 3.

The significance of his conclusions was recognized, and

other biologists immediately began to conduct similar genetic

studies on mice, chickens, and other organisms. The

results of these investigations showed that many traits indeed

follow Mendel’s rules.

Walter Sutton (1877–1916) proposed in 1902 that

genes are located on chromosomes. Thomas Hunt Morgan

(1866–1945) discovered the first genetic mutant of fruit flies

in 1910 and used fruit flies to unravel many details of transmission

genetics. Ronald A. Fisher (1890–1962), John B. S.

Haldane (1892–1964), and Sewall Wright (1889–1988) laid

the foundation for population genetics in the 1930s.

Geneticists began to use bacteria and viruses in the

1940s; the rapid reproduction and simple genetic systems of

these organisms allowed detailed study of the organization

and structure of genes. At about this same time, evidence

accumulated that DNA was the repository of genetic information.

James Watson (b. 1928) and Francis Crick (b. 1916)

described the three-dimensional structure of DNA in 1953,

ushering in the era of molecular genetics.

By 1966, the chemical structure of DNA and the system

by which it determines the amino acid sequence of proteins

had been worked out. Advances in molecular genetics led to

the first recombinant DNA experiments in 1973, which

touched off another revolution in genetic research. Walter

Gilbert (b. 1932) and Frederick Sanger (b. 1918) developed

methods for sequencing DNA in 1977. The polymerase

chain reaction, a technique for quickly amplifying tiny

amounts of DNA, was developed by Kary Mullis (b. 1944)

and others in 1986. In 1990, gene therapy was used for the

first time to treat human genetic disease in the United States

( FIGURE 1.11), and the Human Genome Project was

launched. By 1995, the first complete DNA sequence of a

free-living organism—the bacterium Haemophilus influenzae—

was determined, and the first complete sequence of a

eukaryotic organism (yeast) was reported a year later. At the

beginning of the twenty-first century, the human genome

sequence was determined, ushering in a new era in genetics.

◗

Patient with

genetic disease

Cells

Virus containing

functional gene

1 Cells are removed

from the patient.

3 The cells are then grown

in a culture, tested…

4 …and implanted

into the patient.

2 A new or corrected version

of a gene is added to the

cell, usually with the use of

a genetically engineered virus.

1.11 Gene therapy applies genetic engineering to the

treatment of human diseases. ( J. Coate, MDBD/Science VU/Visuals

Unlimited.)

◗

000 Chapter I

The Future of Genetics

The information content of genetics now doubles every few

years. The genome sequences of many organisms are added

to DNA databases every year, and new details about gene

structure and function are continually expanding our

knowledge of heredity. All of this information provides us

with a better understanding of numerous biological

processes and evolutionary relationships. The flood of new

genetic information requires the continuous development

of sophisticated computer programs to store, retrieve, compare,

and analyze genetic data and has given rise to the field

of bioinformatics, a merging of molecular biology and

computer science.

In the future, the focus of DNA-sequencing efforts will

shift from the genomes of different species to individual differences

within species. It is reasonable to assume that each

person may some day possess a copy of his or her entire

genome sequence. New genetic microchips that simultaneously

analyze thousands of RNA molecules will provide information

about the activity of thousands of genes in a

given cell, allowing a detailed picture of how cells respond

to external signals, environmental stresses, and disease

states. The use of genetics in the agricultural, chemical, and

health-care fields will continue to expand; some predict that

biotechnology will be to the twenty-first century what the

electronics industry was to the twentieth century. This everwidening

scope of genetics will raise significant ethical,

social, and economic issues.

This brief overview of the history of genetics is not

intended to be comprehensive; rather it is designed to provide

a sense of the accelerating pace of advances in genetics.

In the chapters to come, we will learn more about the

experiments and the scientists who helped shape the discipline

of genetics.

More information about the

history of genetics

Basic Concepts in Genetics

Undoubtedly, you learned some genetic principles in other

biology classes. Let’s take a few moments to review some of

these fundamental genetic concepts.

Concepts

Developments in plant hybridization and cytology

in the eighteenth and nineteenth centuries laid the

foundation for the field of genetics today. After

Mendel’s work was rediscovered in 1900, the

science of genetics developed rapidly and today is

one of the most active areas of science.

Cells are of two basic types: eukaryotic and

prokaryotic- Structurally, cells consist of two basic

types, although, evolutionarily, the story is more

complex (see Chapter 2). Prokaryotic cells lack a

nuclear membrane and possess no membranebounded

cell organelles, whereas eukaryotic cells are

more complex, possessing a nucleus and membranebounded

organelles such as chloroplasts and

mitochondria.

A gene is the fundamental unit of heredity- The

precise way in which a gene is defined often varies. At

the simplest level, we can think of a gene as a unit of

information that encodes a genetic characteristic. We

will enlarge this definition as we learn more about

what genes are and how they function.

Genes come in multiple forms called alleles- A gene

that specifies a characteristic may exist in several

forms, called alleles. For example, a gene for coat

color in cats may exist in alleles that encode either

black or orange fur.

Genes encode phenotypes- One of the most

important concepts in genetics is the distinction

between traits and genes. Traits are not inherited

directly. Rather, genes are inherited and, along with

environmental factors, determine the expression of

traits. The genetic information that an individual

organism possesses is its genotype; the trait is its

phenotype. For example, the A blood type is a

phenotype; the genetic information that encodes the

blood type A antigen is the genotype.

Genetic information is carried in DNA and RNAGenetic

information is encoded in the molecular

structure of nucleic acids, which come in two types:

deoxyribonucleic acid (DNA) and ribonucleic acid

(RNA). Nucleic acids are polymers consisting of

repeating units called nucleotides; each nucleotide

consists of a sugar, a phosphate, and a nitrogenous

base. The nitrogenous bases in DNA are of four types

(abbreviated A, C, G, and T), and the sequence of

these bases encodes genetic information. Most

organisms carry their genetic information in DNA,

but a few viruses carry it in RNA. The four

nitrogenous bases of RNA are abbreviated A, C, G,

and U.

Genes are located on chromosomes- The vehicles of

genetic information within the cell are chromosomes

( FIGURE 1.12), which consist of DNA and associated

proteins. The cells of each species have a characteristic

number of chromosomes; for example, bacterial cells

normally possess a single chromosome; human cells

possess 46; pigeon cells possess 80. Each chromosome

carries a large number of genes.