The New Genetics
U.S. DEPARTMENT OF
HEALTH AND HUMAN SERVICES
National Institutes of Health
National Institute of General Medical Sciences
W H AT I S N I G M S? The National Institute of General Medical Sciences (NIGMS) supports basic research on genes, proteins and cells. It also funds studies on fundamental processes such as how cells communicate, how our bodies use energy and how we
respond to medicines. The results of this research increase our understanding of life and lay the foundation for advances in the diagnosis, treatment and prevention of disease. The Institute’s research training programs produce the next generation of scientists, and NIGMS has programs to increase the diversity of the biomedical and behavioral research workforce. NIGMS supported the research of most of the scientists mentioned in this booklet.
Produced by the Office of Communications and Public Liaison National Institute of General Medical Sciences
National Institutes of Health
U.S. Department of Health and Human Services
The New Genetics
NIH Publication No.10 662
Revised April 2010
Contents
F O R E W O R D
2
C H A P T E R 1 : H O W G E N E S W O R K
4
Beautiful DNA
5
Copycat
8
Let’s Call It Even
9
Getting the Message
11
Nature’s CutandPaste Job
14
All Together Now
16
Genetics and You: Nursery Genetics
17
Found in Translation
18
RNA Surprises
19
An Interesting Development
20
The Tools of Genetics: Mighty Microarrays
22
C H A P T E R 2 : R N A A N D D N A R E V E A L E D : N E W R O L E S , N E W R U L E S
2 4
RNA World
25
Molecular Editor
26
Healthy Interference
29
Dynamic DNA
30
Secret Code
30
Genetics and You: The Genetics of Anticipation 32
Battle of the Sexes
33
Starting at the End
34
The Other Human Genome
36
The Tools of Genetics: Recombinant DNA and Cloning 38
C H A P T E R 3 : L I F E ’ S G E N E T I C T R E E
4 0
Everything Evolves
40
Selective Study
42
Clues from Variation
43
Living Laboratories
46
The Genome Zoo
52
Genes Meet Environment
53
Genetics and You: You’ve Got Rhythm!
56
Animals Helping People
58
My Collaborator Is a Computer
58
The Tools of Genetics: Unlimited DNA
60
C H A P T E R 4 : G E N E S A R E U S
6 2
Individualized Prescriptions
64
The Healing Power of DNA
65
Cause and Effect
67
Us vs. Them
68
Genetics and You: Eat Less, Live Longer?
69
Gang Warfare
70
The Tools of Genetics: Mathematics and Medicine 72
C H A P T E R 5 : 2 1 S T C E N T U RY G E N E T I C S
7 4
No Lab? No Problem!
76
Hard Questions
78
Good Advice
80
Genetics and You: CrimeFighting DNA
81
Genetics, Business, and the Law
82
Careers in Genetics
85
The Tools of Genetics: Informatics and Databases 86
G LO S SA RY
8 8
Foreword
Consider
And every living thing
just three of Earth’s inhabitants:
does one thing the same
a bright yellow daffodil that greets the
way: To make more of
itself, it first copies its
spring, the singlecelled creature called
molecular instruction
Thermococcus
manual — its genes — and then passes this inforthat lives in boiling hot mation on to its offspring. This cycle has been
springs, and you. Even a sciencefiction
repeated for three and a half billion years.
But how did we and our very distant relawriter inventing a story set on a distant tives come to look so different and develop so
planet
many different ways of getting along in the
could hardly imagine three more difworld? A century ago, researchers began to answer ferent forms of life. Yet you, Thermococcus
that question with the help of a science called
genetics. Get a refresher course on the basics in
and the daffodil are related! Indeed, all of
Chapter 1, “How Genes Work.”
the
It’s likely that when you think of heredity
Earth’s billions of living things are kin
you think first of DNA, but in the past few years,
to each other.
researchers have made surprising findings about
The New Genetics I Foreword 3
another molecular actor that plays a starring role.
Can DNA and RNA help doctors predict
Check out the modern view of RNA in Chapter 2,
whether we’ll get diseases like cancer, diabetes or
“RNA and DNA Revealed: New Roles, New Rules.”
asthma? What other mysteries are locked within
When genetics first started, scientists didn’t
the 6 feet of DNA inside nearly every cell in our
have the tools they have today. They could only
bodies? Chapter 4, “Genes Are Us,” explains what look at one gene, or a few genes, at a time. Now,
researchers know, and what they are still learning,
researchers can examine all of the genes in a livabout the role of genes in health and disease.
ing organism— its genome — at once. They are
Finally, in Chapter 5, “21stCentury
doing this for organisms on every branch of the
Genetics,” see a preview of things to come. Learn tree of life and finding that the genomes of mice,
how medicine and science are changing in big
frogs, fish and a slew of other creatures have
ways, and how these changes influence society.
many genes similar to our own.
From metabolism to medicines to agriculture,
So why doesn’t your brother look like your
the science of genetics affects us every day. It is
dog or the fish in your aquarium? It’s because of
part of life … part of your life!
evolution. In Chapter 3, “Life’s Genetic Tree,”
find out how evolution works and how it relates
to genetics and medical research.
C H A P T E R 1
How Genes Work
People have known for many years that
Proteins do many other things, too. They
living things inherit traits from their parents.
provide the body’s main building materials,
That commonsense observation led to agriculforming the cell’s architecture and structural ture, the purposeful breeding and cultivation of
components. But one thing proteins can’t do is
animals and plants for desirable characteristics.
make copies of themselves. When a cell needs
Firming up the details took quite some time,
more proteins, it uses the manufacturing instructhough. Researchers did not understand exactly tions coded in DNA.
how traits were passed to the next generation
The DNA code of a gene—the sequence of
until the middle of the 20th century.
its individual DNA building blocks, labeled A
Now it is clear that genes are what carry our
(adenine), T (thymine), C (cytosine) and G
traits through generations and that genes are
(guanine) and collectively called nucleotides—
made of deoxyribonucleic acid (DNA). But
spells out the exact order of a protein’s building
genes themselves don’t do the actual work.
blocks, amino acids.
Rather, they serve as instruction books for mak
Occasionally, there is a kind of typographical
ing functional molecules such as ribonucleic
error in a gene’s DNA sequence. This mistake—
acid (RNA) and proteins, which perform the
which can be a change, gap or duplication— is
chemical reactions in our bodies.
called a mutation.
Genetics in the Garden
In 1900, three European scientists inde
The monk Gregor
Mendel first described
pendently discovered an obscure research
how traits are inherited
paper that had been published nearly 35
from one generation to
years before. Written by Gregor Mendel,
the next.
an Austrian monk who was also a scientist, the report described a series of offspring and learned that these characteristics
breeding experiments performed with pea
were passed on to the next generation in orderly,
plants growing in his abbey garden.
predictable ratios.
Mendel had studied how pea plants
When he crossbred purpleflowered pea plants
inherited the two variant forms of easytosee
with whiteflowered ones, the next generation had
traits. These included flower color (white or purple)
only purple flowers. But directions for making white
and the texture of the peas (smooth or wrinkled).
flowers were hidden somewhere in the peas of that
Mendel counted many generations of pea plant
generation, because when those purpleflowered
The New Genetics I How Genes Work 5
A mutation can cause a gene to encode a
Beautiful DNA
protein that works incorrectly or that doesn’t
Up until the 1950s, scientists knew a good deal
work at all. Sometimes, the error means that no
about heredity, but they didn’t have a clue what
protein is made.
DNA looked like. In order to learn more about
But not all DNA changes are harmful. Some
DNA and its structure, some scientists experimutations have no effect, and others produce mented with using X rays as a form of molecular
new versions of proteins that may give a survival
photography.
advantage to the organisms that have them. Over
Rosalind Franklin, a physical chemist worktime, mutations supply the raw material from ing with Maurice Wilkins at King’s College in
which new life forms evolve (see Chapter 3,
London, was among the first to use this method
“Life’s Genetic Tree”).
to analyze genetic material. Her experiments
plants were bred to each other, some of their offfactors, whatever they were, must be physical spring had white flowers. What’s more, the
material because they passed from parent to
secondgeneration plants displayed the colors in a
offspring in a mathematically orderly way. It wasn’t
predictable pattern. On average, 75 percent of the
until many years later, when the other scientists
secondgeneration plants had purple flowers and
unearthed Mendel’s report, that the factors were
25 percent of the plants had white flowers. Those
named genes.
same ratios persisted, and were reproduced when
Early geneticists quickly discovered that
the experiment was repeated many times over.
Mendel’s mathematical rules of inheritance applied
Trying to solve the mystery of the missing color
not just to peas, but also to all plants, animals and
blooms, Mendel imagined that the reproductive
people. The discovery of a quantitative rule for
cells of his pea plants might contain discrete
inheritance was momentous. It revealed that a
“factors,” each of which specified a particular trait,
common, general principle governed the growth
such as white flowers. Mendel reasoned that the
and development of all life on Earth.
6 National Institute of General Medical Sciences
produced what were referred to at the time as
“the most beautiful Xray photographs of any
COLD SPR
substance ever taken.”
ING HAR
Other scientists, including zoologist James
BOR LAB
Watson and physicist Francis Crick, both work
ORATORY
ing at Cambridge University in the United
ARCHIV
Kingdom, were trying to determine the shape
ES
. In 1953, Watson and Crick created their historic of DNA too. Ultimately, this line of research
model of the shape of DNA: the double helix.
revealed one of the most profound scientific
discoveries of the 20th century: that DNA exists
handrails —were complementary to each other,
as a double helix.
and this unlocked the secret of how genetic
The 1962 Nobel Prize in physiology or mediinformation is stored, transferred and copied.
cine was awarded to Watson, Crick and Wilkins
In genetics, complementary means that if
for this work. Although Franklin did not earn a
you know the sequence of nucleotide building
share of the prize due to her untimely death at age
blocks on one strand, you know the sequence of
38, she is widely recognized as having played a
nucleotide building blocks on the other strand:
significant role in the discovery.
A always matches up with T and C always links
The spiral staircaseshaped double
to G (see drawing, page 7).
helix has attained global status as
Long strings of nucleotides form genes,
the symbol for DNA. But what
and groups of genes are packaged tightly into
is so beautiful about the
structures called chromosomes. Every cell in your
discovery of the twisting
body except for eggs, sperm and red blood cells
ladder structure isn’t just
contains a full set of chromosomes in its nucleus.
its good looks. Rather, the
If the chromosomes in one of your cells were
structure of DNA taught
uncoiled and placed end to end, the DNA would
researchers a fundamental
be about 6 feet long. If all the DNA in your body
lesson about genetics. It taught
were connected in this way, it would stretch
them that the two connected
approximately 67 billion miles! That’s nearly
strands —winding together like parallel
150,000 round trips to the Moon.
. Rosalind Franklin’s
original Xray diffraction
photo revealed the physical
structure of DNA.
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The New Genetics I How Genes Work 7
DNA Structure
The long, stringy DNA that makes up genes is
spooled within chromosomes inside the nucleus
of a cell. (Note that a gene would actually be a much
Chromosome
longer stretch of DNA than what is shown here.)
Nucleus
G
C
Bases
Cell
C
G
A
T
G
C
DNA
Guanine
G
C
Cytosine
A
T
C
G
Thymine
T
A
Adenine
Gene
A
T
Sugar
G
C
phosphate
backbone
C
G
A
T
DNA consists of two long, twisted chains made up
of nucleotides. Each nucleotide contains one base,
one phosphate molecule and the sugar molecule
deoxyribose. The bases in DNA nucleotides are
adenine, thymine, cytosine and guanine.
P
Nucleotide
S
C
8 National Institute of General Medical Sciences
Copycat
It’s astounding to think that
your body consists of trillions
of cells. But what’s most
amazing is that it all starts
with one cell. How does this
massive expansion take place?
As an embryo progresses
. Humans have 23 pairs of chromosomes. Male DNA (pictured here) through development, its cells
contains an X and a Y chromosome, whereas female DNA contains two X chromosomes.
must reproduce. But before
CYTOGENETICS LABORATORY, BRIGHAM AND WOMEN’S HOSPITAL
a cell divides into two new,
nearly identical cells, it must
copy its DNA so there will be a complete set of
the complementary new strand. The process,
genes to pass on to each of the new cells.
called replication, is astonishingly fast and
To make a copy of itself, the twisted, comaccurate, although occasional mistakes, such as pacted double helix of DNA has to unwind and
deletions or duplications, occur. Fortunately, a
separate its two strands. Each strand becomes
cellular spellchecker catches and corrects nearly
a pattern, or template, for making a new strand,
all of these errors.
so the two new DNA molecules have one new
Mistakes that are not corrected can lead to
strand and one old strand.
diseases such as cancer and certain genetic disor
The copy is courtesy of a cellular protein
ders. Some of these include Fanconi anemia, early
machine called DNA polymerase, which reads
aging diseases and other conditions in which
the template DNA strand and stitches together
people are extremely sensitive to sunlight and
some chemicals.
DNA copying is not the only time when DNA
damage can happen. Prolonged, unprotected sun
exposure can cause DNA changes that lead to
skin cancer, and toxins in cigarette smoke can
cause lung cancer.
. When DNA polymerase makes an error while copying a gene’s DNA sequence, the mistake is called a mutation. In this example, the nucleotide G has been changed to an A.
The New Genetics I How Genes Work 9
C G
A
T
C
G
It may seem ironic, then, that many drugs
A
T
used to treat cancer work by attacking DNA. That’s
T
A
because these chemotherapy drugs disrupt the
DNA copying process, which goes on much faster
C
G