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1
GENETICS
AND THE ORGANISM

KEY QUESTIONS
• What is the hereditary material?
• What is the chemical and physical structure
of DNA?
• How is DNA copied in the formation of new
cells and in the gametes that will give rise to
the offspring of an individual?
• What are the functional units of DNA that
carry information about development and
physiology?
• What molecules are the main determinants
of the basic structural and physiological
properties of an organism?
• What are the steps in translating the
information in DNA into protein?
• What determines the differences between
species in their physiology and structure?
• What are the causes of variation between
individuals within species?
Genetic variation in the color of corn kernels. Each kernel • What is the basis of variation in
represents a separate individual with a distinct genetic
makeup. The photograph symbolizes the history of humanity’s
populations?
interest in heredity. Humans were breeding corn thousands of
years before the advent of the modern discipline of genetics. OUTLINE
Extending this heritage, corn today is one of the main
research organisms in classical and molecular genetics. 1.1 Genes as determinants of the inherent
[William Sheridan, University of North Dakota; photograph by Travis properties of species
Amos.]
1.2 Genetic variation
1.3 Methodologies used in genetics
1.4 Model organisms
1.5 Genes, the environment, and the organism

1
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2 Chapter 1 • Genetics and the Organism

CHAPTER OVERVIEW features are clearly familial; for example, animals of

a certain unique color often have offspring with the
hy study genetics? There are two basic reasons. same color, and in human families, certain features,
W First, genetics occupies a pivotal position in the
entire subject of biology. Therefore, for any serious stu-
such as the shape of the nose, definitely “run in the
family.” Hence we might suspect that a hereditary
dent of plant, animal, or microbial life, an understanding component explains at least some of the variation
of genetics is essential. Second, genetics, like no other within a species.
scientific discipline, is central to numerous aspects of hu-
man affairs. It touches our humanity in many different The answer to the first question is that genes dictate
ways. Indeed, genetic issues seem to surface daily in our the inherent properties of a species. The products of
lives, and no thinking person can afford to be ignorant of most genes are specific proteins. Proteins are the main
its discoveries. In this chapter, we take an overview of macromolecules of an organism. When you look at an
the science of genetics, showing how it has come to oc- organism, what you see is either a protein or something
cupy its crucial position. In addition, we provide a per- that has been made by a protein. The amino acid se-
spective from which to view the subsequent chapters. quence of a protein is encoded in a gene. The timing and
First, we need to define what genetics is. Some define rate of production of proteins and other cellular compo-
it as the “study of heredity,” but hereditary phenomena nents are a function both of the genes within the cells
were of interest to humans long before biology or genet- and of the environment in which the organism is devel-
ics existed as the scientific disciplines that we know to- oping and functioning.
day. Ancient peoples were improving plant crops and The answer to the second question is that any one
domesticated animals by selecting desirable individuals gene can exist in several forms that differ from one an-
for breeding. They also must have puzzled about the in- other, generally in small ways. These forms of a gene are
heritance of individuality in humans and asked such called alleles. Allelic variation causes hereditary variation
questions as “Why do children resemble their parents?” within a species. At the protein level, allelic variation be-
and “How can various diseases run in families?” But comes protein variation.
these people could not be called “geneticists.” Genetics
as a set of principles and analytical procedures did not
begin until the 1860s, when an Augustinian monk
named Gregor Mendel (Figure 1-1) performed a set of
experiments that pointed to the existence of biological
elements that we now call genes. The word genetics
comes from the word “gene,” and genes are the focus of
the subject. Whether geneticists study at the molecular,
cellular, organismal, family, population, or evolutionary
level, genes are always central in their studies. Simply
stated, genetics is the study of genes.
What is a gene? A gene is a section of a threadlike
double-helical molecule called deoxyribonucleic acid,
abbreviated DNA. The discovery of genes and the un-
derstanding of their molecular structure and function
have been sources of profound insight into two of the
biggest mysteries of biology:

1. What makes a species what it is? We know that cats

always have kittens and people always have babies.
This commonsense observation naturally leads to
questions about the determination of the properties
of a species. The determination must be hereditary
because, for example, the ability to have kittens is
inherited by every generation of cats.
2. What causes variation within a species? We can
distinguish one another as well as our own pet cat
from other cats. Such differences within a species
require explanation. Some of these distinguishing Figure 1-1 Gregor Mendel. [Moravian Museum, Brno.]
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1.1 Genes as determinants of the inherent properties of species 3

The next sections of this chapter show how genes

Testes Ovaries
influence the inherent properties of a species and how
allelic variation contributes to variation within a species. DNA DNA
REPLICATION REPLICATION
These sections are an overview; most of the details will
be presented in later chapters.
Division of gonad Division of gonad
cells cells
1.1 Genes as determinants
of the inherent properties Sperm Egg

of species
Zygote
What is the nature of genes, and how do they perform
their biological roles? Three fundamental properties
are required of genes and the DNA of which they are DNA
REPLICATION
composed.

1. Replication. Hereditary molecules must be capable Division of

of being copied at two key stages of the life cycle asexual (body)
(Figure 1-2). The first stage is the production of the cells
cell type that will ensure the continuation of a
species from one generation to the next. In plants Repeat
and animals, these cells are the gametes: egg and divisions
sperm. The other stage is when the first cell of a
new organism undergoes multiple rounds of division
to produce a multicellular organism. In plants and
animals, this is the stage at which the fertilized egg,
the zygote, divides repeatedly to produce the
complex organismal appearance that we recognize.
Figure 1-2 DNA replication is the basis of the perpetuation of
2. Generation of form. The working structures that life through time.
make up an organism can be thought of as form or
substance, and DNA has the essential “information”
needed to create form. cell’s production of proteins. Each chromosome in the
3. Mutation. A gene that has changed from one allelic genome carries a different array of genes. In diploid cells,
form into another has undergone mutation — an each chromosome and its component genes are present
event that happens rarely but regularly. Mutation is twice. For example, human somatic cells contain two
not only a basis for variation within a species, but sets of 23 chromosomes, for a total of 46 chromosomes.
also, over the long term, the raw material for Two chromosomes with the same gene array are said to
evolution. be homologous. When a cell divides, all its chromosomes
(its one or two copies of the genome) are replicated and
We will examine replication and the generation of then separated, so that each daughter cell receives the
form in this section and mutation in the next. full complement of chromosomes.
To understand replication, we need to understand
the basic nature of DNA. DNA is a linear, double-helical
DNA and its replication structure that looks rather like a molecular spiral stair-
An organism’s basic complement of DNA is called its case. The double helix is composed of two intertwined
genome. The somatic cells of most plants and animals chains made up of building blocks called nucleotides.
contain two copies of their genome (Figure 1-3); these Each nucleotide consists of a phosphate group, a
organisms are diploid. The cells of most fungi, algae, and deoxyribose sugar molecule, and one of four different
bacteria contain just one copy of the genome; these or- nitrogenous bases: adenine, guanine, cytosine, or
ganisms are haploid. The genome itself is made up of thymine. Each of the four nucleotides is usually desig-
one or more extremely long molecules of DNA that are nated by the first letter of the base it contains: A, G, C,
organized into chromosomes. Genes are simply the re- or T. Each nucleotide chain is held together by bonds
gions of chromosomal DNA that are involved in the between the sugar and phosphate portions of the
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4 Chapter 1 • Genetics and the Organism

Figure 1-3 Successive

enlargements bringing the genetic gene
material of an organism into sharper gene
focus.
gene

Organism Each cell Each

(human) nucleus One specific chromosome DNA is a
A human body contains an is one long DNA double helix.
chromosome
is made up identical molecule, and
pair
of trillions complement of genes are
of cells. chromosomes functional regions
in two copies. of this DNA.
Each copy
is a genome.

consecutive nucleotides, which form the “backbone” of bases that form base pairs are said to be complementary.
the chain. The two intertwined chains are held together Hence a short segment of DNA drawn with arbitrary
by weak bonds between bases on opposite chains (Fig- nucleotide sequence might be
ure 1-4). There is a “lock-and-key” fit between the bases
· · · ·CAGT· · · ·
on the opposite strands, such that adenine pairs only
· · · ·GTCA· · · ·
with thymine and guanine pairs only with cytosine. The

MESSAGE DNA is composed of two nucleotide chains

held together by complementary pairing of A with T and G
with C.

For replication of DNA to take place, the two

strands of the double helix must come apart, rather like
the opening of a zipper. The two exposed nucleotide
chains then act as alignment guides, or templates, for the
deposition of free nucleotides, which are then joined to-
gether by the enzyme DNA polymerase to form a new
strand. The crucial point illustrated in Figure 1-5 is that
because of base complementarity, the two daughter
DNA molecules are identical with each other and with
the original molecule.

MESSAGE DNA is replicated by the unwinding of the two

strands of the double helix and the building up of a new
complementary strand on each of the separated strands of the
original double helix.

Generation of form
If DNA represents information, what constitutes form at
the cellular level? The simple answer is “protein” be-
cause the great majority of structures in a cell are pro-
tein or have been made by protein. In this section, we
trace the steps through which information becomes
form.
The biological role of most genes is to carry infor-
mation specifying the chemical composition of proteins
or the regulatory signals that will govern their produc-
tion by the cell. This information is encoded by the se-
Figure 1-4 Ribbon representation of the DNA double helix. quence of nucleotides. A typical gene contains the infor-
Blue  sugar-phosphate backbone; brown  paired bases. mation for one specific protein. The collection of
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1.1 Genes as determinants of the inherent properties of species 5

Figure 1-5 DNA T S P P P

replication in process. S S
S P S P S P S P S T G
Blue  nucleotides of P S P P P
the original double helix; A T G C C T P
P

S
gold  new nucleotides

A
P P

P
T A C G G S Original DNA double helix
being polymerized A
P
to form daughter chains. Identical P S P S P S P S P S P A S P S P S P S P S P
S
S  sugar; daughter C C T G A
DNA DNA
P  phosphate group. double
Direction
polymerase
helices G G A C T
P
forming S P S P S P S P S P S P S P S P S P S P S

T
T

P
A T G C C P
T

P
P
A P

P
T A C G G S
P P

S
S P S P
P S P S P S P S P

C
P
S Free nucleotides
A
P

A S

proteins an organism can synthesize, as well as the tim- contains uracil (U), which like thymine, pairs with ade-
ing and amount of production of each protein, is an ex- nine. Hence the RNA bases are A, G, C, and U. The tran-
tremely important determinant of the structure and scription process, which occurs in the cell nucleus, is
physiology of organisms. A protein generally has one of very similar to the process for replication of DNA be-
two basic functions, depending on the gene. First, the cause the DNA strand serves as the template for making
protein may be a structural component, contributing to the RNA copy, which is called a transcript. The RNA
the physical properties of cells or organisms. Examples transcript, which in many species undergoes some struc-
of structural proteins are microtubule, muscle, and hair tural modifications, becomes a “working copy” of the in-
proteins. Second, the protein may be an active agent in formation in the gene, a kind of “message” molecule
cellular processes — such as an active-transport protein called messenger RNA (mRNA). The mRNA then en-
or an enzyme that catalyzes one of the chemical reac- ters the cytoplasm, where it is used by the cellular
tions of the cell. machinery to direct the manufacture of a protein. Fig-
The primary structure of a protein is a linear chain ure 1-6 summarizes the process of transcription.
of amino acids, called a polypeptide. The sequence of
amino acids in the primary chain is specified by the se-
MESSAGE During transcription, one of the DNA strands
quence of nucleotides in the gene. The completed pri- of a gene acts as a template for the synthesis of a
mary chain is coiled and folded — and in some cases, as- complementary RNA molecule.
sociated with other chains or small molecules — to form
a functional protein. A given amino acid sequence may
fold in a large number of stable ways. The final folded TRANSLATION The process of producing a chain of
state of a protein depends both on the sequence of amino acids based on the sequence of nucleotides in the
amino acids specified by its gene and on the physiology mRNA is called translation. The nucleotide sequence of
of the cell during folding. an mRNA molecule is “read” from one end of the
mRNA to the other, in groups of three successive bases.
These groups of three are called codons.
MESSAGE The sequence of nucleotides in a gene
specifies the sequence of amino acids that is put together AUU CCG UAC GUA AAU UUG
by the cell to produce a polypeptide. This polypeptide then
codon codon codon codon codon codon
folds under the influence of its amino acid sequence and other
molecular conditions in the cell to form a protein.
Because there are four different nucleotides, there are
4  4  4  64 different codons possible, each one
TRANSCRIPTION The first step taken by the cell to coding for an amino acid or a signal to terminate transla-
make a protein is to copy, or transcribe, the nucleotide tion. Because only 20 kinds of amino acids are used in
sequence in one strand of the gene into a complemen- the polypeptides that make up proteins, more than one
tary single-stranded molecule called ribonucleic acid codon may correspond to the same amino acid. For in-
(RNA). Like DNA, RNA is composed of nucleotides, stance, AUU, AUC, and AUA all encode isoleucine, while
but these nucleotides contain the sugar ribose instead of UUU and UUC code for phenylalanine, and UAG is a
deoxyribose. Furthermore, in place of thymine, RNA translation termination (“stop”) codon.
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6 Chapter 1 • Genetics and the Organism

Polypeptide aa1
aa2
aa3
aa4 aa8
DNA
Nucleus
tRNA aa5

aa6 aa7
Primary
Transcription RNA
transcript

RNA processing
Codon Codon Codon Codon Codon Codon Codon
4 5 6 7 8 9 10

Mature mRNA
Amino acid Figure 1-7 Translation. An amino acid (aa) is added to a
chain Transport to growing polypeptide chain in the translation of mRNA.
cytoplasm

mRNA GENE REGULATION Let’s take a closer look at the

structure of a gene, which determines the final form of
Translation the RNA “working copy” as well as the timing of tran-
Ribosome scription in a particular tissue. Figure 1-8 shows the gen-
eral structure of a gene. At one end, there is a regulatory
region to which various proteins involved in the regula-
Figure 1-6 Transcription and translation in a eukaryotic cell. tion of the gene’s transcription bind, causing the gene to
The mRNA is processed in the nucleus, then transported to
be transcribed at the right time and in the right amount.
the cytoplasm for translation into a polypeptide chain.
A region at the other end of the gene signals the end
point of the gene’s transcription. Between these two end
Protein synthesis takes place on cytoplasmic organelles
regions lies the DNA sequence that will be transcribed
called ribosomes. A ribosome attaches to one end of an
to specify the amino acid sequence of a polypeptide.
mRNA molecule and moves along the mRNA, catalyzing
Gene structure is more complex in eukaryotes than
the assembly of the string of amino acids that will consti-
in prokaryotes. Eukaryotes, which include all the multi-
tute the primary polypeptide chain of the protein. Each
cellular plants and animals, are those organisms whose
kind of amino acid is brought to the assembly process by a
cells have a membrane-bound nucleus. Prokaryotes are
small RNA molecule called transfer RNA (tRNA), which
organisms with a simpler cellular structure lacking a nu-
is complementary to the mRNA codon that is being read
cleus, such as bacteria. In the genes of many eukaryotes,
by the ribosome at that point in the assembly.
the protein-encoding sequence is interrupted by one or
Trains of ribosomes pass along an mRNA molecule,
more stretches of DNA called introns. The origin and
each member of a train making the same type of polypep-
functions of introns are still unclear. They are excised
tide. At the end of the mRNA, a termination codon causes
from the primary transcript during the formation of
the ribosome to detach and recycle to another mRNA.
mRNA. The segments of coding sequence between the
The process of translation is shown in Figure 1-7.
introns are called exons.
Some protein-encoding genes are transcribed more
MESSAGE The information in genes is used by the cell in or less constantly; these are the “housekeeping” genes
two steps of information transfer: DNA is transcribed into that are always needed for basic reactions. Other genes
mRNA, which is then translated into the amino acid sequence
of a polypeptide. The flow of information from DNA to RNA to
may be rendered unreadable or readable to suit the
protein is a central focus of modern biology. functions of the organism at particular times and under
particular external conditions. The signal that masks or
Gene

Transcribed region

Exon Intron Exon Intron Exon Intron Exon

Figure 1-8 Generalized structure
of a eukaryotic gene. This
Regulation of Termination example has three introns and
initiation of of transcription four exons.
transcription
Protein-encoding sequence
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1.1 Genes as determinants of the inherent properties of species 7

unmasks a gene may come from outside the cell, for ex- Figure 1-9 Simplified view of gene action in a eukaryotic cell.
ample, from a steroid hormone or a nutrient. Alterna- The basic flow of genetic information is from DNA to RNA to
tively, the signal may come from within the cell as the protein. Four types of genes are shown. Gene 1 responds to
result of the reading of other genes. In either case, external regulatory signals and makes a protein for export;
gene 2 responds to internal signals and makes a protein for
special regulatory sequences in the DNA are directly
use in the cytoplasm; gene 3 makes a protein to be
affected by the signal, and they in turn affect the
transported into an organelle; gene 4 is part of the organelle
transcription of the protein-encoding gene. The regu- DNA and makes a protein for use inside its own organelle.
latory substances that serve as signals bind to the regula- Most eukaryotic genes contain introns, regions (generally
tory region of the target gene to control the synthesis of noncoding) that are cut out in the preparation of functional
transcripts. messenger RNA. Note that many organelle genes have introns
Figure 1-9 illustrates the essentials of gene action in a and that an RNA-synthesizing enzyme is needed for organelle
generalized eukaryotic cell. Outside the nucleus of the cell mRNA synthesis. These details have been omitted from the
is a complex array of membranous structures, including diagram of the organelle for clarity. (Introns will be
explained in detail in subsequent chapters.)

External
Gene 1 Nuclear chromosomes
signal

Internal signal
Gene 2

Intron
removal
Nuclear Gene 3
membrane
mRNA 1

mRNA 2 mRNA 3

Endoplasmic reticulum

mRNA 4
Golgi apparatus
Gene 4

Circular organelle chromosome

Mitochondrion or chloroplast

Cell membrane Key

Protein-coding region of DNA RNA polymerase
Noncoding region Secreted protein
Protein-coding region of RNA Proteins used in cell
Noncoding region Protein encoded by
mitochondrion or chloroplast
Promoter Amino acid chain
Regulatory proteins Ribosome
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8 Chapter 1 • Genetics and the Organism

the endoplasmic reticulum and Golgi apparatus, and or- 1.2 Genetic variation
ganelles such as mitochondria and chloroplasts. The nu-
cleus contains most of the DNA, but note that mitochon- If all members of a species have the same set of genes,
dria and chloroplasts also contain small chromosomes. how can there be genetic variation? As indicated earlier,
Each gene encodes a separate protein, each with spe- the answer is that genes come in different forms called
cific functions either within the cell (for example, the alleles. In a population, for any given gene there can be
purple-rectangle proteins in Figure 1-9) or for export to from one to many different alleles; however, because
other parts of the organism (the purple-circle proteins). most organisms carry only one or two chromosome sets
The synthesis of proteins for export (secretory proteins) per cell, any individual organism can carry only one or
takes place on ribosomes that are located on the surface two alleles per gene. The alleles of one gene will always
of the rough endoplasmic reticulum, a system of large, be found in the same position along the chromosome.
flattened membrane vesicles. The completed amino acid Allelic variation is the basis for hereditary variation.
chains are passed into the lumen of the endoplasmic
reticulum, where they fold up spontaneously to take on Types of variation
their three-dimensional structure. The proteins may be
modified at this stage, but they eventually enter the Because a great deal of genetics concerns the analysis of
chambers of the Golgi apparatus and from there, the se- variants, it is important to understand the types of varia-
cretory vessels, which eventually fuse with the cell mem- tion found in populations. A useful classification is into
brane and release their contents to the outside. discontinuous and continuous variation (Figure 1-10). Al-
Proteins destined to function in the cytoplasm and lelic variation contributes to both.
most of the proteins that function in mitochondria and
chloroplasts are synthesized in the cytoplasm on ribo- DISCONTINUOUS VARIATION Most of the research in
somes not bound to membranes. For example, proteins genetics in the past century has been on discontinuous
that function as enzymes in the glycolysis pathway fol- variation because it is a simpler type of variation, and it
low this route. The proteins destined for organelles are is easier to analyze. In discontinuous variation, a charac-
specially tagged to target their insertion into specific or- ter is found in a population in two or more distinct and
ganelles. In addition, mitochondria and chloroplasts separate forms called phenotypes. “Blue eyes” and
have their own small circular DNA molecules. The syn- “brown eyes” are phenotypes, as is “blood type A” or
thesis of proteins encoded by genes on mitochondrial or “blood type O.” Such alternative phenotypes are often
chloroplast DNA takes place on ribosomes inside the found to be encoded by the alleles of one gene. A good
organelles themselves. Therefore the proteins in mito- example is albinism in humans, which concerns pheno-
chondria and chloroplasts are of two different origins: types of the character of skin pigmentation. In most peo-
either encoded in the nucleus and imported into the or- ple, the cells of the skin can make a dark-brown or black
ganelle or encoded in the organelle and synthesized pigment called melanin, the substance that gives our skin
within the organelle compartment. its color ranging from tan color in people of European
ancestry to brown or black in those of tropical and sub-
tropical ancestry. Although always rare, albinos, who
MESSAGE The flow of information from DNA to RNA to
protein is a central focus of modern biology. completely lack pigment in their skin and hair, are found
in all races (Figure 1-11). The difference between pig-
2 mm

(a) Wingless fruit Winged fruit (b)

Figure 1-10 Examples of discontinuous and continuous variation in natural populations.

(a) Fruits of the sea blush, Plectritis congesta, have one of two distinct forms. Any one
plant has either all winged or all wingless fruits. (b) Variation in height, branch number,
and flower number in the herb Achillea. [Part b, Carnegie Institution of Washington.]
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1.2 Genetic variation 9

phenotype under most conditions. In other words, the

two phenotypes (and their underlying genotypes) can
almost always be distinguished. In the albinism exam-
ple, the A allele always allows some pigment forma-
tion, whereas the a allele always results in albinism
when present in two copies. For this reason, discontinu-
ous variation has been successfully used by geneticists
to identify the underlying alleles and their role in cellu-
lar functions.
Geneticists distinguish two categories of discontin-
uous variation. In a natural population, the existence of
two or more common discontinuous variants is called
polymorphism (Greek; many forms). The various forms
are called morphs. It is often found that different
morphs are determined by different alleles of a single
gene. Why do populations show genetic polymor-
phism? Special types of natural selection can explain a
few cases, but, in other cases, the morphs seem to be
selectively neutral.
Figure 1-11 An albino. The phenotype is caused by two doses Rare, exceptional discontinuous variants are called
of a recessive allele, a /a. The dominant allele A determines
mutants, whereas the more common “normal” pheno-
one step in the chemical synthesis of the dark pigment
type is called the wild type. Figure 1-12 shows an ex-
melanin in the cells of skin, hair, and eye retinas. In a /a
individuals, this step is nonfunctional, and the synthesis of ample of a mutant phenotype. Again, in many cases,
melanin is blocked. [Copyright Yves Gellie/Icone.] the wild-type and mutant phenotypes are determined
by different alleles of one gene. Both mutants and poly-
morphisms originally arise from rare changes in DNA
mented and unpigmented skin is caused by different al- (mutations), but somehow the mutant alleles of a poly-
leles of a gene that encodes an enzyme involved in morphism become common. These rare changes in
melanin synthesis. DNA may be nucleotide-pair substitutions or small
The alleles of a gene are conventionally designated deletions or duplications. Such mutations change the
by letters. The allele that codes for the normal form of amino acid composition of the protein. In the case of
the enzyme involved in making melanin is called A, and albinism, for example, the DNA of a gene that encodes
the allele that codes for an inactive form of that enzyme an enzyme involved in melanin synthesis is changed,
(resulting in albinism) is designated a, to show that they such that a crucial amino acid is replaced by another
are related. The allelic constitution of an organism is its amino acid or lost, yielding a nonfunctioning enzyme.
genotype, which is the hereditary underpinning of the Mutants (such as those that produce albinism) can oc-
phenotype. Because humans have two sets of chromo- cur spontaneously in nature, or they can be produced
somes in each cell, genotypes can be either A/A, A/a, or by treatment with mutagenic chemicals or radiation.
a/a (the slash shows that the two alleles are a pair). The Geneticists regularly induce mutations artificially to
phenotype of A/A is pigmented, that of a/a is albino,
and that of A/a is pigmented. The ability to make pig-
ment is expressed over inability (A is said to be domi-
nant, as we shall see in Chapter 2).
Although allelic differences cause phenotypic differ-
ences such as pigmented and albino coloration, this does
not mean that only one gene affects skin color. It is
known that there are several, although the identity
and number of these genes are currently unknown.
However, the difference between pigmented, of whatever
shade, and albinism is caused by the difference in the al-
Wild type Vestigial wings
leles of one gene — the gene that determines the ability
to make melanin; the allelic composition of other genes Figure 1-12 Wild type and mutant Drosophila. A Drosophila
is irrelevant. mutant with abnormal wings and a normal fly (wild type) for
In some cases of discontinuous variation, there is a comparison. In both cases, the two phenotypes are caused by
predictable one-to-one relation between genotype and the alleles of one gene.
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10 Chapter 1 • Genetics and the Organism

carry out genetic analysis because mutations that affect enzymes — tyrosinase. The enzyme tyrosinase catalyzes
some specific biological function under study identify the last step of the pathway, the conversion of tyrosine
the various genes that interact in that function. into melanin.
To perform this task, tyrosinase binds to its sub-
MESSAGE In many cases, an allelic difference at a single
strate, a molecule of tyrosine, and facilitates the molecu-
gene may result in discrete phenotypic forms that make it lar changes necessary to produce the pigment melanin.
easy to study the gene and its associated biological function. There is a specific “lock-and-key” fit between tyrosine
and the active site of the enzyme. The active site is a
pocket formed by several crucial amino acids in the
CONTINUOUS VARIATION A character showing contin- polypeptide. If the DNA of the tyrosinase-encoding gene
uous variation has an unbroken range of phenotypes in a changes in such a way that one of these crucial amino
population (see Figure 1-10b). Measurable characters acids is replaced by another amino acid or is lost, then
such as height, weight, and skin or hair color are good there are several possible consequences. First, the en-
examples of such variation. Intermediate phenotypes are zyme might still be able to perform its functions but in a
generally more common than extreme phenotypes. In less efficient manner. Such a change may have only a
some cases, all the variation is environmental and has no small effect at the phenotypic level, so small as to be dif-
genetic basis, as in the case of the different languages ficult to observe, but it might lead to a reduction in the
spoken by different human groups. In other cases, such amount of melanin formed and, consequently, a lighter
as that of the various shades of human eye color, the dif- skin coloration. Note that the protein is still present
ferences are caused by allelic variation in one or many more or less intact, but its ability to convert tyrosine
genes. For most continuously variable characters, both into melanin has been compromised. Second, the en-
genetic and environmental variation contribute to differ- zyme might be incapable of any function, in which case
ences in phenotype. In continuous variation, there is no the mutational event in the DNA of the gene would
one-to-one correspondence of genotype and phenotype. have produced an albinism allele, referred to earlier as
For this reason, little is known about the types of genes an a allele. Hence a person of genotype a/a is an albino.
underlying continuous variation, and only recently have The genotype A/a is interesting. It results in normal pig-
techniques become available for identifying and charac- mentation because transcription of one copy of the wild-
terizing them. type allele (A) can provide enough tyrosinase for synthe-
Continuous variation is encountered more com- sis of normal amounts of melanin. Genes are termed
monly than discontinuous variation in everyday life. We haplosufficient if roughly normal function is obtained
can all identify examples of continuous variation, such as when there is only a single copy of the normal gene.
variation in size or shape, in plant or animal populations Wild-type alleles commonly appear to be haplosuffi-
that we have observed — many examples exist in human
cient, in part because small reductions in function are
populations. One area of genetics in which continuous
not vital to the organism. Alleles that fail to code for a
variation is important is in plant and animal breeding.
functional protein are called null (“nothing”) alleles and
Many of the characters that are under selection in
are generally not expressed in combination with func-
breeding programs, such as seed weight or milk produc-
tional alleles (in individuals of genotype A/a). The mole-
tion, arise from many gene differences interacting with
cular basis of albinism is represented in Figure 1-13.
environmental variation, and the phenotypes show con-
Third, more rarely, the altered protein may perform its
tinuous variation in populations. We shall return to the
function more efficiently and thus be the basis for future
specialized techniques for analyzing continuous varia-
evolution by natural selection.
tion in Chapter 20, but for the greater part of the book,
The mutational site in the DNA can be of a number
we shall be dealing with the genes underlying discontin-
of types. The simplest and most common type is
uous variation.
nucleotide-pair substitution, which can lead to amino
acid substitution or to premature stop codons. Small
Molecular basis of allelic variation deletions and duplications also are common. Even a sin-
Consider the difference between the pigmented and the gle base deletion or insertion produces widespread dam-
albino phenotypes in humans. The dark pigment age at the protein level; because mRNA is read from one
melanin has a complex structure that is the end product end “in frame” in groups of three, a loss or gain of one
of a biochemical synthetic pathway. Each step in the nucleotide pair shifts the reading frame, and all the
pathway is a conversion of one molecule into another, amino acids translationally downstream will be incor-
with the progressive formation of melanin in a step-by- rect. Such mutations are called frameshift mutations.
step manner. Each step is catalyzed by a separate At the protein level, mutation changes the amino
enzyme protein encoded by a specific gene. Most cases acid composition of the protein. The most important
of albinism result from changes in one of these outcomes are change in protein shape and size. Such
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1.3 Methodologies used in genetics 11

Genotype A /A Nucleus of Genotype A /a Genotype a /a

melanocyte
Normal Normal Mutant
allele A allele A allele a

Normal Mutant Mutant

allele A allele a allele a

Transcripts

Polypeptides

Tyrosinase Mutant
Tyr
enzyme active site
(inactive)

No melanin
Melanin Melanin

Phenotype of
melanocyte Pigmented Pigmented Albino

Figure 1-13 Molecular basis of albinism. Left: Melanocytes (pigment-producing cells)

containing two copies of the normal tyrosinase allele (A) produce the tyrosinase enzyme,
which converts the amino acid tyrosine into the pigment melanin Center: Melanocytes
containing one copy of the normal allele make enough tyrosinase to allow production of
melanin and the pigmented phenotype. Right: Melanocytes containing two copies of
the mutant null allele (a) are unable to produce any of the enzyme.

change in shape or size can result in an absence of bio- only hereditary mechanisms, but all biological mecha-
logical function (which would be the basis of a null al- nisms. Many different methodologies are used to study
lele) or reduced function. More rarely, mutation can lead genes and gene activities, and these methodologies can
to new function of the protein product. be summarized briefly as follows:

1. Isolation of mutations affecting the biological

MESSAGE New alleles formed by mutation can result in
no function, less function, more function, or new function process under study. Each mutant gene reveals a
at the protein level. genetic component of the process, and together the
mutant genes show the range of proteins that
interact in that process.
1.3 Methodologies used 2. Analysis of progeny of controlled matings (“crosses”)
in genetics between mutants and wild-type individuals or other
discontinuous variants. This type of analysis
An overview identifies genes and their alleles, their chromosomal
The study of genes has proved to be a powerful ap- locations, and their inheritance patterns. These
proach to understanding biological systems. Because methods will be introduced in Chapter 2.
genes affect virtually every aspect of the structure and 3. Genetic analysis of the cell’s biochemical processes.
function of an organism, being able to identify and de- Life is basically a complex set of chemical reactions,
termine the role of genes and the proteins that they so studying the ways in which genes are relevant to
specify is an important step in charting the various these reactions is an important way of dissecting this
processes that underlie a particular character under in- complex chemistry. Mutant alleles underlying
vestigation. It is interesting that geneticists study not defective function (see method 1) are invaluable in
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12 Chapter 1 • Genetics and the Organism

this type of analysis. The basic approach is to find fluorescent compound, so that the site of binding can
out how the cellular chemistry is disturbed in the easily be detected. Let’s look at probes for DNA, RNA,
mutant individual and, from this information, and protein.
deduce the role of the gene. The deductions from
many genes are assembled to reveal the larger PROBING FOR A SPECIFIC DNA A cloned gene can
picture. act as a probe for finding segments of DNA that have
4. Microscopic analysis. Chromosome structure and the same or a very similar sequence. For example, if a
movement have long been an integral part of gene G from a fungus has been cloned, it might be of
genetics, but new technologies have provided ways interest to determine whether plants have the same
of labeling genes and gene products so that their gene. The use of a cloned gene as a probe takes us back
locations can be easily visualized under the to the principle of base complementarity. The probe
microscope. works through the principle that, in solution, the ran-
5. Direct analysis of DNA. Because the genetic dom motion of probe molecules enables them to find
material is composed of DNA, the ultimate and bind to complementary sequences. The experi-
characterization of a gene is the analysis of the DNA ment must be done with separated DNA strands, be-
sequence itself. Many techniques, including gene cause then the bonding sites of the bases are unoccu-
cloning, are used to accomplish this. Cloning is a pied. DNA from the plant is extracted and cut with
procedure by which an individual gene can be one of the many available types of restriction enzymes,
isolated and amplified (copied multiple times) to which cut DNA at specific target sequences of four or
produce a pure sample for analysis. One way of more bases. The target sequences are at the same posi-
doing this is by inserting the gene of interest into a tions in all the plant cells used, so the enzyme cuts the
small bacterial chromosome and allowing bacteria to genome into defined populations of segments of spe-
do the job of copying the inserted DNA. After the cific sizes. The fragments can be separated into groups
clone of a gene has been obtained, its nucleotide of fragments of the same length (fractionated) by using
sequence can be determined, and hence important electrophoresis.
information about its structure and function can be Electrophoresis fractionates a population of nucleic
obtained. acid fragments on the basis of size. The cut mixture is
placed in a small well in a gelatinous slab (a gel), and the
Entire genomes of many organisms have been se- gel is placed in a powerful electrical field. The electricity
quenced by extensions of the above techniques, thereby causes the molecules to move through the gel at speeds
giving rise to a new discipline within genetics called inversely proportional to their size. After fractionation,
genomics, the study of the structure, function, and evo- the separated fragments are blotted onto a piece of
porous membrane, where they maintain the same rela-
lution of whole genomes. Part of genomics is bioinfor-
tive positions. This procedure is called a Southern blot.
matics, the mathematical analysis of the information
After having been heated to separate the DNA strands
content of genomes.
and hold the DNA in position, the membrane is placed
in a solution of the probe. The single-stranded probe will
Detecting specific molecules of DNA, find and bind to its complementary DNA sequence. For
RNA, and protein example,
Whether studying genes individually or as genomes,
geneticists often need to detect the presence of a spe- TAGGTATCG Probe
cific molecule each of DNA, RNA, or protein, the ACTAATCCATAGCTTA Genomic fragment
main macromolecules of genetics. These techniques
will be described fully in Chapter 11, but we need a On the blot, this binding concentrates the label in one
brief overview of them that can be used in earlier spot, as shown in the left panel of Figure 1-14.
chapters.
How can specific molecules be identified among the PROBING FOR A SPECIFIC RNA It is often necessary to
thousands of types in the cell? The most extensively determine whether a gene is being transcribed in some
used method for detecting specific macromolecules in a particular tissue. For this purpose, a modification of the
mixture is probing. This method makes use of the speci- Southern analysis is useful. Total mRNA is extracted
ficity of intermolecular binding, which we have already from the tissue, fractionated electrophoretically, and
encountered several times. A mixture of macromolecules blotted onto a membrane (this procedure is called a
is exposed to a molecule — the probe — that will bind Northern blot). The cloned gene is used as a probe,
only with the sought-after macromolecule. The probe is and its label will highlight the mRNA in question if it is
labeled in some way, either by a radioactive atom or by a present (middle panel of Figure 1-14).
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1.4 Model organisms 13

Chromosomal DNA Gene P species. Even for the features that vary, however, that
variation is always between major groups of living forms,
so that we do not have to investigate the basic phenom-
ena of genetics over and over again for every species. In
Cut DNA fragment mRNA Protein product P fact, all the phenomena of genetics have been investi-
to be detected to be detected to be detected gated by experiments on a small number of species,
model organisms, whose genetic mechanisms are com-
mon either to all species or to a large group of related
organisms.
Total cut DNA Total mRNA Total protein
Electro-
phoresis Lessons from the first model organisms
The use of model organisms goes back to the work of
Gregor Mendel, who used crosses between horticultural
Fraction- varieties of the garden pea, Pisum sativum, to establish
ation
the basic rules of inheritance. Mendel’s use of these vari-
eties of the garden pea is instructive for our understand-
ing of both the strengths and weaknesses of studying
(a) Southern blot (b) Northern blot (c) Western blot
model organisms. Mendel studied the inheritance of
three character differences: tall versus short plant height,
purple versus white flowers, and round versus wrinkled
seeds. These are all inherited as simple, single-gene dif-
Gene ferences. Hybrids between the varieties with contrasting
Gene P
P mRNA Gene characters were always identical with one of the two
fragment P
protein parents, while the hybrids produced some offspring
showing one of the original parental types and some
showing the other parental type in repeatable ratios. So,
Blot probed with Blot probed with Blot probed with a cross between a purple variety and a white variety pro-
cloned gene P cloned gene P antibody to protein P
(labeled) (labeled) (labeled)
duced purple hybrids, while a cross between hybrids
produced purple and white progeny in a ratio of 3 : 1.
Figure 1-14 Probing DNA, RNA, and protein mixtures. Moreover, if two varieties differed in two of the traits,
one trait difference, say, purple versus white, was inde-
pendent in its inheritance of the other trait, say, tall ver-
sus short. As a result of his observations, Mendel pro-
PROBING FOR A SPECIFIC PROTEIN Probing for pro- posed three “laws” of inheritance:
teins is generally performed with antibodies because an
antibody has a specific lock-and-key fit with its protein
1. The law of segregation: alternative trait “factors” that
target, or antigen. The protein mixture is separated into
came together in the offspring separate again when
bands of distinct proteins by electrophoresis and blotted
the offspring produce gametes.
onto a membrane (this procedure is a Western blot).
The position of a specific protein on the membrane is 2. The law of dominance: hybrids between two
revealed by bathing the membrane in a solution of anti- alternative forms of a trait resemble one of the
body, obtained from a rabbit or other host into which parental types.
the protein has been injected. The position of the pro- 3. The law of independent assortment: differences for
tein is revealed by the position of the label that the anti- one trait are inherited independently of differences
body carries (right-hand panel of Figure 1-14). for another trait.

1.4 Model organisms These laws were the foundation for genetics and, in
particular, established that the mechanism of inheritance
The science of genetics discussed in this book is meant was based on discrete particles in the gametes that come
to provide an understanding of features of inheritance together in an offspring and then separate again when
and development that are characteristic of organisms in the offspring produces gametes, rather than by the mix-
general. Some of these features, especially at the molec- ing of a continuous fluid. But Mendel could not have in-
ular level, are true of all known living forms. For others ferred this mechanism had he studied height variation in
there is some variation between large groups of organ- most plant varieties, where such variation is continuous,
isms, for example, between bacteria and all multicellular because it depends on many gene differences. Moreover,
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14 Chapter 1 • Genetics and the Organism

the law of dominance does not hold true for many trait The diploid product of this fusion may reproduce by cell
differences in many species. Indeed, had Mendel studied division and colony formation, but is eventually fol-
flower color in the sweet pea, Lathyrus odoratus, he lowed by meiosis and the production of haploid spores
would have observed pink-flowered offspring from the that give rise to new haploid colonies. Saccharomyces
cross between a red and a white variety, and would not cerevisiae is the usual model species.
have observed the existence of dominance. Finally, many
traits, even in the garden pea, do not show independent Filamentous fungi In these fungi nuclear division and
inheritance, but are linked together on chromosomes. growth produces long, branching threads separated irreg-
ularly into “cells” by membranes and cell walls, but a sin-
The need for a variety of model organisms gle such cellular compartment may contain more than
one haploid nucleus. A fusion of two filaments will result
While the use of a particular model organism can reveal in a diploid nucleus that then undergoes meiosis to pro-
quite general features of inheritance and development, duce a fruiting body of haploid cells. In the fungi, Neuro-
we cannot know how general such features are unless spora is the standard model organism (Figure 1-15b) be-
experiments are carried out on a variety of inherited cause its fruiting body (see Chapter 3) contains eight
traits in a variety of model organisms with very different spores in a linear array, reflecting the pairing of chromo-
patterns of reproduction and development. somes and the synthesis of new chromosomal strands
Model organisms have been chosen partly for their during meiosis.
different basic biological properties, and partly for small The importance of bacteria, yeasts, and filamentous
size of individuals, short generation time, and the ease fungi for genetics lies in their basic biochemistry. For
with which they can be grown and mated under simple their metabolism and growth they require only a carbon
controlled conditions. For the study of vertebrate genet- source such as sugar, a few minerals such as calcium, and
ics, mice are to be preferred to elephants. in some cases a vitamin like biotin. All the other chemi-
The need to study a wide range of biological and ge- cal components of the cell, including all amino acids and
netic traits has led to an array of model organisms from nucleotides, are synthesized by their cell machinery.
each of the basic biological groups (Figure 1-15). Thus it is possible to study the effects of genetic changes
in the most basic biochemical pathways.
VIRUSES These are simple nonliving particles that lack
all metabolic machinery. They infect a host cell and di- Multicellular organisms For the genetic study of the dif-
vert its biosynthetic apparatus to the production of ferentiation of cells, tissues, and organs, as well as the de-
more virus, including the replication of viral genes. The velopment of body form, it is necessary to use more
viruses infecting bacteria, called bacteriophage, are the complex organisms. These organisms must be easy to
standard model (Figure 1-15a). The chief use of viruses culture under controlled conditions, have life cycles
has been to study the physical and chemical structure of short enough to allow breeding experiments over many
DNA and the fundamental mechanics of DNA replica- generations, and be small enough to make the produc-
tion and mutation. tion of large numbers of individuals practical. The main
model organisms that fill these requirements are
PROKARYOTES These single-celled living organisms
have no nuclear membrane and lack intracellular com- • Arabidopsis thaliana, a small flowering plant that can
partments. While there is a special form of mating and be cultured in large numbers in the greenhouse or
genetic exchange between prokaryotic cells, they are es- laboratory (Figure 1-15c). It has a small genome
sentially haploid throughout their lifetimes. The gut bac- contained in only five chromosomes. It is an ideal
terium Escherichia coli is the common model. So con- model for studying the development of higher plants
vinced were some E. coli geneticists of the general and the comparison of animal and plant development
applicability of their model organism that one university and genome structure.
department’s postage meter printed a stylized E. coli cell • Drosophila melanogaster, a fruit fly with only four
rearranged to look like an elephant. chromosomes. In the larval stage these chromosomes
have a well-marked pattern of banding that makes it
EUKARYOTES All other cellular life is made up of one possible to observe physical changes such as deletions
or more cells with a nuclear membrane and cellular and duplications, which can then be correlated with
compartments. genetic changes in morphology and biochemistry. The
development of Drosophila produces body segments
Yeasts Yeasts are single-celled fungi that usually repro- in an anterior-posterior order that is an example of
duce by division of haploid cells to form colonies, but the basic body plan common to invertebrates and
may also reproduce sexually by the fusion of two cells. vertebrates.
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1.4 Model organisms 15

(a)

(b)

(c) (d)

Figure 1-15 Some model organisms. (a) Bacteriophage  attached to an infected

E. coli cell; progeny phage particles are maturing inside the cell. (b) Neurospora growing
on a burnt tree after a forest fire. (c) Arabidopsis. (d) Caenorhabditis elegans. [Part a,
Lee D. Simon/Science Source/Photo Researchers; part b, courtesy of David Jacobson; part c,
Wally Eberhart/Visuals Unlimited; part d, AFP/CORBIS.]

• Caenorhabditis elegans, a tiny roundworm with a total interactions in utero, and in understanding the
of only a few thousand adult cells. These form a genetics of cancer.
nervous system; a digestive tract with a mouth,
The genomes of all the model organisms discussed
pharynx, and anus; and a reproductive system that
above have been sequenced. Despite the great differ-
can produce both eggs and sperm (Figure 1-15d).
ences in biology there are many similarities in their
• Mus musculus, the house mouse, the model organism genomes. Figure 1-16 is a comparison of the genomes of
for vertebrates. It has been studied to compare the eukaryotes, prokaryotes, and viruses.
genetic basis of vertebrate and invertebrate At the end of the book we summarize and compare
development as well as to explore the genetics of the inferences made about genetics from the use of the
antigen-antibody systems, of maternal-fetal various models.
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16 Chapter 1 • Genetics and the Organism

Fungi Protists

Eukaryotic cell

Animals Plants
Nuclear chromosomes
Chloroplast
Mitochondrial
chromosome
chromosome
(plants)

DNA DNA

Gene Gene Gene Gene Gene

DNA-protein supercoil

DNA

Gene Gene Gene

Prokaryotic cell
Bacteria Bacterial Viruses
chromosome
Plasmid

DNA

Gene

DNA DNA

Gene Gene Gene Gene Gene

Figure 1-16 Structural comparison of the genome components of eukaryotes, prokaryotes, and viruses.

1.5 Genes, the environment, vides the raw materials for the synthetic processes con-
trolled by genes. An acorn becomes an oak tree, by using
and the organism in the process only water, oxygen, carbon dioxide, some
inorganic materials from the soil, and light energy.
Genes cannot dictate the structure of an organism by
themselves. The other crucial component in the formula is
Model I: genetic determination
the environment. The environment influences gene action
in many ways, about which we shall learn in subsequent It is clear that virtually all the differences between
chapters. Most concretely perhaps, the environment pro- species are determined by the differences in their
44200_01_p1-26 3/2/04 4:01 PM Page 17

1.5 Genes, the environment, and the organism 17

genomes. There is no environment in which a lion will Genetic “blueprint”

give birth to a lamb. An acorn develops into an oak,
whereas the spore of a moss develops into a moss, even Organism A
if both are growing side by side in the same forest. The
two plants that result from these developmental Environment 1
Plan A
processes resemble their parents and differ from each
other, even though they have access to the same narrow
range of materials from the environment. Environment 2
Even within species, some variation is entirely a con-
sequence of genetic differences that cannot be modified Plan B
by any change in what we normally think of as environ- Environment 3
ment. The children of African slaves brought to North
America had dark skins, unchanged by the relocation of Organism B
their parents from tropical Africa to temperate Mary-
land. The possibility of much of experimental genetics
depends on the fact that many of the phenotypic differ- Figure 1-17 A model of determination that emphasizes the role
ences between mutant and wild-type individuals result- of genes.
ing from allelic differences are insensitive to environ-
mental conditions. The determinative power of genes is genes are really the dominant elements in phenotypic
often demonstrated by differences in which one allele is determination; the environment simply supplies the un-
normal and the other abnormal. The human inherited differentiated raw materials.
disease sickle-cell anemia is a good example. The under-
lying cause of the disease is a variant of hemoglobin, the Model II: environmental determination
oxygen-transporting protein molecule found in red Consider two monozygotic (“identical”) twins, the prod-
blood cells. Normal people have a type of hemoglobin ucts of a single fertilized egg that divided and produced
called hemoglobin-A, the information for which is en- two complete babies with identical genes. Suppose that
coded in a gene. A single nucleotide change in the DNA the twins are born in England but are separated at birth
of this gene, leading to a change in a single amino acid in and taken to different countries. If one is reared in China
the polypeptide, results in the production of a slightly by Chinese-speaking foster parents, she will speak Chi-
changed hemoglobin, called hemoglobin-S. In people pos- nese, whereas her sister reared in Budapest will speak
sessing only hemoglobin-S, the ultimate effect of this Hungarian. Each will absorb the cultural values and cus-
small change in DNA is severe ill health — sickle-cell toms of her environment. Although the twins begin life
anemia — and often death. with identical genetic properties, the different cultural
Such observations, if generalized, lead to a model, environments in which they live will produce differ-
shown in Figure 1-17, of how genes and the environ- ences between them (and differences from their par-
ment interact. In this view, the genes act as a set of in- ents). Obviously, the differences in this case are due to
structions for turning more or less undifferentiated envi- the environment, and genetic effects are of no impor-
ronmental materials into a specific organism, much as tance in determining the differences.
blueprints specify what form of house is to be built from This example suggests the model of Figure 1-18,
basic materials. The same bricks, mortar, wood, and nails which is the converse of that shown in Figure 1-17. In
can be made into an A-frame or a flat-roofed house, ac- the model in Figure 1-18, the genes impinge on the sys-
cording to different plans. Such a model implies that the tem, giving certain general signals for development, but

Environmental factor 1
Environment A Environmental factor 2 Organism A
Environmental factor 3
General
genetic rules
Environmental factor 4
Figure 1-18
A model of
Environment B Environmental factor 5 Organism B determination
Environmental factor 6 that emphasizes
the role of the
environment.
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18 Chapter 1 • Genetics and the Organism

the environment determines the actual course of devel- the individual characteristics themselves are inherited:
opment. Imagine a set of specifications for a house that “He gets his brains from his mother” or “She inherited di-
simply calls for a “floor that will support 300 pounds per abetes from her father.” Yet the preceding section shows
square foot” or “walls with an insulation factor of 15 that such statements are inaccurate. “His brains” and “her
inches”; the actual appearance and other characteristics diabetes” develop through long sequences of events in the
of the structure would be determined by the available life histories of the affected people, and both genes and
building materials. environment play roles in those sequences. In the biologi-
cal sense, individuals inherit only the molecular structures
Model III: genotype-environment interaction of the fertilized eggs from which they develop. Individu-
als inherit their genes, not the end products of their indi-
In general, we deal with organisms that differ in both
vidual developmental histories.
genes and environment. If we wish to predict how a living
To prevent such confusion between genes (which
organism will develop, we need to know both the genetic
are inherited) and developmental outcomes (which are
constitution that it inherits from its parents and the his-
not), geneticists make the fundamental distinction be-
torical sequence of environments to which it has been ex-
tween the genotype and the phenotype of an organism.
posed. Every organism has a developmental history from
Organisms have the same genotype in common if they
conception to death. What an organism will become in
have the same set of genes. Organisms have the same
the next moment depends critically both on its present
phenotype if they look or function alike.
state and on the environment that it encounters during
Strictly speaking, the genotype describes the com-
that moment. It makes a difference to an organism not
plete set of genes inherited by an individual, and the phe-
only what environments it encounters, but also in what
notype describes all aspects of the individual’s morphol-
sequence it encounters them. A fruit fly (Drosophila
ogy, physiology, behavior, and ecological relations. In this
melanogaster), for example, develops normally at 25˚C. If
sense, no two individuals ever belong to the same phe-
the temperature is briefly raised to 37˚C early in its pupal
notype, because there is always some difference (how-
stage of development, the adult fly will be missing part of
ever slight) between them in morphology or physiology.
the normal vein pattern on its wings. However, if this
Additionally, except for individuals produced from an-
“temperature shock” is administered just 24 hours later,
other organism by asexual reproduction, any two organ-
the vein pattern develops normally. A general model in
isms differ at least a little in genotype. In practice, we
which genes and the environment jointly determine (by
use the terms genotype and phenotype in a more re-
some rules of development) the actual characteristics of
stricted sense. We deal with some partial phenotypic de-
an organism is depicted in Figure 1-19.
scription (say, eye color) and with some subset of the
genotype (say, the genes that affect eye pigmentation).
MESSAGE As an organism transforms developmentally
from one stage to another, its genes interact with its
environment at each moment of its life history. The interaction MESSAGE When we use the terms phenotype and
of genes and environment determines what organisms are. genotype, we generally mean “partial phenotype” and
“partial genotype,” and we specify one or a few traits and
genes that are the subsets of interest.
The use of genotype and phenotype
In light of the preceding discussion we can now better Note one very important difference between geno-
understand the use of the terms genotype and phenotype. type and phenotype: the genotype is essentially a fixed
A typical organism resembles its parents more than it character of an individual organism; the genotype re-
resembles unrelated individuals. Thus, we often speak as if mains constant throughout life and is essentially un-

Developmental
interactions

Type A Organism A I
Genes
Figure 1-19 Type B Organism B I
A model of
determination Type I Organism A II
that emphasizes
Environment
the interaction
Type II Organism B II
of genes and
environment.
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1.5 Genes, the environment, and the organism 19

changed by environmental effects. Most phenotypes more extensive tabulated data. The size of the fly eye is
change continually throughout the life of an organism as measured by counting its individual facets, or cells. The
its genes interact with a sequence of environments. Fix- vertical axis of the graph shows the number of facets (on
ity of genotype does not imply fixity of phenotype. a logarithmic scale); the horizontal axis shows the con-
stant temperature at which the flies develop.
Norm of reaction Three norms of reaction are shown on the graph.
How can we quantify the relation between the geno- When flies of the wild-type genotype that is characteris-
type, the environment, and the phenotype? For a partic- tic of flies in natural populations are raised at higher
ular genotype, we could prepare a table showing the temperatures, they develop eyes that are somewhat
phenotype that would result from the development of smaller than those of wild-type flies raised at cooler
that genotype in each possible environment. Such a set temperatures. The graph shows that wild-type pheno-
of environment-phenotype relations for a given geno- types range from more than 700 to 1000 facets — the
type is called the norm of reaction of the genotype. In wild-type norm of reaction. A fly that has the ultrabar
practice, we can make such a tabulation only for a par- genotype has smaller eyes than those of wild-type flies
tial genotype, a partial phenotype, and some particular regardless of temperature during development. Temper-
aspects of the environment. For example, we might atures have a stronger effect on development of ultrabar
specify the eye sizes that fruit flies would have after de- genotypes than on wild-type genotypes, as we see by
veloping at various constant temperatures; we could do noticing that the ultrabar norm of reaction slopes more
this for several different eye-size genotypes to get the steeply than the wild-type norm of reaction. Any fly of
norms of reaction of the species. the infrabar genotype also has smaller eyes than those of
Figure 1-20 represents just such norms of reaction any wild-type fly, but temperatures have the opposite ef-
for three eye-size genotypes in the fruit fly Drosophila fect on flies of this genotype; infrabar flies raised at
melanogaster. The graph is a convenient summary of higher temperatures tend to have larger eyes than those

Wild type Infrabar Ultrabar

(b)

1000
900
800 Wild type
700
600
(a) 500
400
Number of facets

Figure 1-20 Norms of reaction to

300
temperature for three different eye-
Infrabar
size genotypes in Drosophila.
(a) Close-up showing how the normal 200
eye comprises hundreds of units
called facets. The number of facets
determines eye size. (b) Relative eye
sizes of wild-type, infrabar, and 100
90 Ultrabar
ultrabar flies raised at the higher 80
end of the temperature range. 70
(c) Norm-of-reaction curves for the 60
three genotypes. [Part a, Don Rio 50
0 15 20 25 30
and Sima Misra, University of
California, Berkeley.] (c) Temperature (°C)
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20 Chapter 1 • Genetics and the Organism

of flies raised at lower temperatures. These norms of re-

action indicate that the relation between genotype and
phenotype is complex rather than simple.

MESSAGE A single genotype may produce different

phenotypes, depending on the environment in which
organisms develop. The same phenotype may be produced
by different genotypes, depending on the environment.

If we know that a fruit fly has the wild-type genotype,

this information alone does not tell us whether its eye
has 800 or 1000 facets. On the other hand, the knowl-
edge that a fruit fly’s eye has 170 facets does not tell us
whether its genotype is ultrabar or infrabar. We cannot
even make a general statement about the effect of tem-
perature on eye size in Drosophila, because the effect is
opposite in two different genotypes. We see from Figure
1-20 that some genotypes do differ unambiguously in
phenotype, no matter what the environment: any wild- (a)
type fly has larger eyes than any ultrabar or infrabar fly.
High elevation
But other genotypes overlap in phenotypic expression: 50
the eyes of an ultrabar fly may be larger or smaller than
those of an infrabar fly, depending on the temperatures
at which the individuals developed.
To obtain a norm of reaction such as the norms of
reaction in Figure 1-20, we must allow different individ-
uals of identical genotype to develop in many different
environments. To carry out such an experiment, we
must be able to obtain or produce many fertilized eggs 0
with identical genotypes. For example, to test a human Medium elevation
50
genotype in 10 environments, we would have to obtain
genetically identical sibs and raise each individual in a
Height (cm)

different milieu. However, that is possible neither bio-

logically nor ethically. At the present time, we do not
know the norm of reaction of any human genotype for
any character in any set of environments. Nor is it clear
how we can ever acquire such information without the
unacceptable manipulation of human individuals. 0
Low elevation
For a few experimental organisms, special genetic 50
methods make it possible to replicate genotypes and thus
to determine norms of reaction. Such studies are particu-
larly easy in plants that can be propagated vegetatively
(that is, by cuttings). The pieces cut from a single plant all
have the same genotype, so all offspring produced in this
way have identical genotypes. Such a study has been done
on the yarrow plant, Achillea millefolium (Figure 1-21a).
The experimental results are shown in Figure 1-21b. 0 1 2 3 4 5 6 7
Many plants were collected, and three cuttings were Parental plant (source of cuttings)
taken from each plant. One cutting from each plant was (b)
planted at low elevation (30 meters above sea level), one
Figure 1-21 A comparison of genotype versus phenotype in
at medium elevation (1400 meters), and one at high ele- yarrow. (a) Achillea millefolium. (b) Norms of reaction to
vation (3050 meters). Figure 1-21b shows the mature in- elevation for seven different Achillea plants (seven different
dividuals that developed from the cuttings of seven genotypes). A cutting from each plant was grown at low,
plants; each set of three plants of identical genotype is medium, and high elevations. [Part a, Harper Horticultural Slide
aligned vertically in the figure for comparison. Library; part b, Carnegie Institution of Washington.]
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1.5 Genes, the environment, and the organism 21

First, we note an average effect of environment: in Developmental noise

general, the plants grew poorly at the medium elevation.
Thus far, we have assumed that a phenotype is uniquely
This is not true for every genotype, however; the cutting
determined by the interaction of a specific genotype and a
of plant 4 grew best at the medium elevation. Second,
specific environment. But a closer look shows some fur-
we note that no genotype is unconditionally superior in
ther unexplained variation. According to Figure 1-20, a
growth to all others. Plant 1 showed the best growth at
Drosophila of wild-type genotype raised at 16˚C has 1000
low and high elevations but showed the poorest growth
facets in each eye. In fact, this is only an average value;
at the medium elevation. Plant 6 showed the second-
one fly raised at 16˚C may have 980 facets, and another
worst growth at low elevation and the second-best at
may have 1020. Perhaps these variations are due to slight
high elevation. Once again, we see the complex relation
fluctuations in the local environment or slight differences
between genotype and phenotype. Figure 1-22 graphs
in genotypes. However, a typical count may show that a
the norms of reaction derived from the results shown in
wild-type fly has, say, 1017 facets in the left eye and 982
Figure 1-21b. Each genotype has a different norm of re-
in the right eye. In another wild-type fly raised in the
action, and the norms cross one another; so we cannot
same experimental conditions, the left eye has slightly
identify either a “best” genotype or a “best” environment
fewer facets than the right eye. Yet the left and right eyes
for Achillea growth.
of the same fly are genetically identical. Furthermore, un-
We have seen two different patterns of reaction
der typical experimental conditions, the fly develops as a
norms. The difference between the wild-type and the
larva (a few millimeters long) burrowing in homogeneous
other eye-size genotypes in Drosophila is such that the
artificial food in a laboratory bottle and then completes its
corresponding phenotypes show a consistent difference,
development as a pupa (also a few millimeters long)
regardless of the environment. Any fly of wild-type
glued vertically to the inside of the glass high above the
genotype has larger eyes than any fly of the other geno-
food surface. Surely the environment does not differ sig-
types; so we could (imprecisely) speak of “large eye” and
nificantly from one side of the fly to the other. If the two
“small eye” genotypes. In this case, the differences in
eyes experience the same sequence of environments and
phenotype between genotypes are much greater than
are identical genetically, then why is there any phenotypic
the variation within a genotype caused by development
difference between the left and right eyes?
in different environments. But the variation for a single
Differences in shape and size are partly dependent
Achillea genotype in different environments is so great
on the process of cell division that turns the zygote into
that the norms of reaction cross one another and form
a multicellular organism. Cell division, in turn, is sensi-
no consistent pattern. In this case, it makes no sense to
tive to molecular events within the cell, and these events
identify a genotype with a particular phenotype except
may have a relatively large random component. For ex-
in regard to response to particular environments.
ample, the vitamin biotin is essential for Drosophila
growth, but its average concentration is only one mole-
cule per cell. Obviously, the rate of any process that de-
pends on the presence of this molecule will fluctuate as
the concentration varies. Fewer eye facets may develop if
50 the availability of biotin by chance fluctuates downward
within the relatively short developmental period during
3 1 which the eye is being formed. Thus, we would expect
40
Plant height (cm)

4
random variation in such phenotypic characters as the
2 number of eye cells, the number of hairs, the exact
30 shape of small features, and the connections of neurons
6
in a very complex central nervous system — even when
5
the genotype and the environment are precisely fixed.
20
7 Random events in development lead to variation in
phenotype called developmental noise.
10
MESSAGE In some characteristics, such as eye cells in
0 Drosophila, developmental noise is a major source of the
30 1400 3000 observed variations in phenotype.
Elevation (m)

Figure 1-22 Graphic representation of the complete set of Adding developmental noise to our model of pheno-
results of the type shown in Figure 1-21. Each line represents typic development, we obtain something like Figure 1-23.
the norm of reaction of one plant. With a given genotype and environment, there is a range
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22 Chapter 1 • Genetics and the Organism

Figure 1-23 A model of Noisy

development
phenotypic determination
that shows how genes, Organism 1
environment, and
Type A Organism 2
developmental noise
Genes Organism 3
interact to produce a
phenotype. Type B
Organism 4
Organism 5
Organism 6
Organism 7
Organism 8
Organism 9
Type I
Environment Organism 10
Type II Organism 11
Organism 12

of possible outcomes for each developmental step. The de- variation is important, and developmental genetics has
velopmental process does contain feedback systems that concentrated on understanding them.
tend to hold the deviations within certain bounds so that At a second level of development, there are variations
the range of deviation does not increase indefinitely on the basic developmental themes that are different be-
through the many steps of development. However, this tween species but are constant within species, and these
feedback is not perfect. For any given genotype developing too could be understood by concentrating on genes, al-
in any given sequence of environments, there remains some though at the moment they are not part of the study of
uncertainty regarding the exact phenotype that will result. developmental genetics. So, although both lions and
lambs have four legs, one at each corner, lions always give
Three levels of development birth to lions and lambs to lambs, and we have no diffi-
Chapter 18 of this book is concerned with the way in culty in distinguishing between them in any environment.
which genes mediate development, but nowhere in that Again, we are entitled to say that genes “determine” the
chapter do we consider the role of the environment or difference between the two species, although we must be
the influence of developmental noise. How can we, at more cautious here. Two species may differ in some char-
the beginning of the book, emphasize the joint role of acteristic because they live in quite different environ-
genes, environment, and noise in influencing phenotype, ments, and until we can raise them in the same environ-
yet in our later consideration of development ignore the ment, we cannot always be sure whether environmental
environment? The answer is that modern developmental influence plays a role. For example, two species of ba-
genetics is concerned with very basic processes of differ- boons in Africa, one living in the very dry plains of
entiation that are common to all individual members of Ethiopia and the other in the more productive areas of
a species and, indeed, are common to animals as differ- Uganda, have very different food-gathering behavior and
ent as fruit flies and mammals. How does the front end social structure. Without actually transplanting colonies of
of an animal become differentiated from the back end, the two species between the two environments, we can-
the ventral from the dorsal side? How does the body be- not know how much of the difference is a direct response
come segmented, and why do limbs form on some seg- of these primates to different food conditions.
ments and not on others? Why do eyes form on the head It is at the third level, the differences in morphology,
and not in the middle of the abdomen? Why do the an- physiology, and behavior between individuals within
tennae, wings, and legs of a fly look so different even species, that genetic, environmental, and developmental
though they are derived in evolution from appendages noise factors become intertwined, as discussed in this
that looked alike in the earliest ancestors of insects? At chapter. One of the most serious errors in the understand-
this level of development, which is constant across indi- ing of genetics by nongeneticists has been confusion be-
viduals and species, normal environmental variation tween variation at this level and variation at the higher
plays no role, and we can speak correctly of genes “deter- levels. The experiments and discoveries to be discussed in
mining” the phenotype. Precisely because the effects of Chapters 18 are not, and are not meant to be, models for
genes can be isolated at this level of development and the causation of individual variation. They apply directly
precisely because the processes seem to be general only to those characteristics, deliberately chosen, that are
across a wide variety of organisms, they are easier to general features of development and for which environ-
study than are characteristics for which environmental mental variation appears to be irrelevant.
44200_01_p1-26 3/2/04 4:01 PM Page 23

Summary 23

KEY QUESTIONS REVISITED

• What is the hereditary material? • What are the steps in translating the information in
The molecule DNA. DNA into protein?
For most genes, first, transcription of the DNA sequence
• What is the chemical and physical structure of DNA?
into mRNA, then translation of the RNA sequence into
It is a double helix of two chains of nucleotides, inter- the amino acid sequence of protein.
twined in opposite orientation. At the center of the helix,
nucleotides with G pair with C, and those with A pair • What determines the differences between species in
with T. their physiology and structure?
For the most part, differences between species are the
• How is DNA copied in the formation of new cells and
consequences of species differences in DNA, reflected in
in the gametes that will give rise to the offspring of an
species differences in the structure of proteins and the
individual?
timing and cell localization of their production.
The strands separate, and each is used as a template for
building a new strand. • What are the causes of variation between individuals
within species?
• What are the functional units of DNA that carry Variation between individuals within species is the re-
information about development and physiology? sult of genetic differences, environmental differences,
The functional units are genes, regional units bearing the and the interaction between genes and environment, as
appropriate signal sequences for being transcribed into well as developmental noise.
RNA.
• What is the basis of variation in populations?
• What molecules are the main determinants of the basic Variation among individuals is a consequence of both
structural and physiological properties of an organism? genetic and environmental variation and of random
Many thousands of different types of proteins. events during cell division during development.

SUMMARY
Genetics is the study of genes at all levels from molecules lelic constitution) or by phenotype (observable character-
to populations. As a modern discipline, it began in the istics of appearance or physiology). Both genotypes and
1860s with the work of Gregor Mendel, who first formu- phenotypes show variation within a population. Variation
lated the idea that genes exist. We now know that a gene is of two types: discontinuous, showing two or more dis-
is a functional region of the long DNA molecule that con- tinct phenotypes, and continuous, showing phenotypes
stitutes the fundamental structure of a chromosome. with a wide range of quantitative values. Discontinuous
DNA is composed of four nucleotides, each containing variants are often determined by alleles of one gene. For
deoxyribose sugar, phosphate, and one of four bases : ade- example, people with normal skin pigmentation have the
nine (A), thymine (T), guanine (G), and cytosine (C). functional allele coding for the enzyme tyrosinase, which
DNA is two nucleotide chains, oriented in opposite direc- converts tyrosine into the dark pigment melanin, whereas
tions (antiparallel) and held together by bonding A with T albinos have a mutated form of the gene that codes for a
and G with C. In replication, the two chains separate, and protein that can no longer make the conversion.
their exposed bases are used as templates for the synthesis The relation of genotype to phenotype across an en-
of two identical daughter DNA molecules. vironmental range is called the norm of reaction. In the
Most genes encode the structure of a protein (pro- laboratory, geneticists study discontinuous variants under
teins are the main determinants of the properties of an conditions where there is a one-to-one correspondence
organism). To make protein, DNA is first transcribed by between genotype and phenotype. However, in natural
the enzyme RNA polymerase into a single-stranded work- populations, where environment and genetic background
ing copy called messenger RNA (mRNA). The nucleotide vary, there is generally a more complex relation, and
sequence in the mRNA is translated into an amino acid genotypes can produce overlapping ranges of phenotypes.
sequence that constitutes the primary structure of a pro- As a result, discontinuous variants have been the starting
tein. Amino acid chains are synthesized on ribosomes. point for most experiments in genetic analysis.
Each amino acid is brought to the ribosome by a tRNA The main tools of genetics are breeding analysis of
molecule that docks by the binding of its triplet (called variants, biochemistry, microscopy, and direct analysis of
the anticodon) to a triplet codon in mRNA. DNA using cloned DNA. Cloned DNA can provide use-
The same gene may have alternative forms called al- ful probes for detecting the presence of related DNA
leles. Individuals may be classified by genotype (their al- and RNA.