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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
F O R E W O R D
C H A P T E R 1 : H O W G E N E S W O R K
Let’s Call It Even
Getting the Message
Nature’s CutandPaste Job
All Together Now
Genetics and You: Nursery Genetics
Found in Translation
An Interesting Development
The Tools of Genetics: Mighty Microarrays
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
Genetics and You: The Genetics of Anticipation 32
Battle of the Sexes
Starting at the End
The Other Human Genome
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
Clues from Variation
The Genome Zoo
Genes Meet Environment
Genetics and You: You’ve Got Rhythm!
Animals Helping People
My Collaborator Is a Computer
The Tools of Genetics: Unlimited DNA
C H A P T E R 4 : G E N E S A R E U S
The Healing Power of DNA
Cause and Effect
Us vs. Them
Genetics and You: Eat Less, Live Longer?
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
No Lab? No Problem!
Genetics and You: CrimeFighting DNA
Genetics, Business, and the Law
Careers in Genetics
The Tools of Genetics: Informatics and Databases 86
G LO S SA RY
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
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
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.”
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,
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.
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
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
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
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
substance ever taken.”
Other scientists, including zoologist James
Watson and physicist Francis Crick, both work
ing at Cambridge University in the United
Kingdom, were trying to determine the shape
. 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.
OREGON STATE UNIVERSITY LIBRARIES
The New Genetics I How Genes Work 7
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
longer stretch of DNA than what is shown here.)
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.
8 National Institute of General Medical Sciences
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
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
It may seem ironic, then, that many drugs
used to treat cancer work by attacking DNA. That’s
because these chemotherapy drugs disrupt the
DNA copying process, which goes on much faster
in rapidly dividing cancer cells than in other
cells of the body. The trouble is that most of these
drugs do affect normal cells that grow and
divide frequently, such as cells of the immune
system and hair cells.
Understanding DNA replication better could
be a key to limiting a drug’s action to cancer
Let’s Call It Even
After copying its DNA, a cell’s next challenge is
getting just the right amount of genetic material
into each of its two offspring.
Most of your cells are called diploid
(“di” means two, and “ploid” refers to sets of
chromosomes) because they have two sets of
chromosomes (23 pairs). Eggs and sperm are
different; these are known as haploid cells. Each
haploid cell has only one set of 23 chromosomes
so that at fertilization the math will work out:
A haploid egg cell will combine with a haploid
sperm cell to form a diploid cell with the right
number of chromosomes: 46.
Chromosomes are numbered 1 to 22,
according to size, with 1 being the largest
chromosome. The 23rd pair, known as the sex
. During DNA replication, each strand of the
original molecule acts as a template for
chromosomes, are called X and Y. In humans,
the synthesis of a new, complementary
abnormalities of chromosome number usually
occur during meiosis, the time when a cell
10 National Institute of General Medical Sciences Meiosis
During meiosis, chromosomes
from both parents are copied
and paired to exchange portions
This creates a mix of new genetic
material in the offspring’s cells.
sections of DNA
Nucleus divides into
Chromosome pairs divide
daughter nuclei have
and a new mix of
The New Genetics I How Genes Work 11
reduces its chromosomes from diploid to haploid
Amon has made major progress in underin creating eggs or sperm.
standing the details of meiosis. Her research shows
What happens if an egg or a sperm cell gets
how, in healthy cells, gluelike protein complexes
the wrong number of chromosomes, and how
called cohesins release pairs of chromosomes at
often does this happen?
exactly the right time. This allows the chromo
Molecular biologist Angelika Amon of
somes to separate properly.
the Massachusetts Institute of Technology in
These findings have important implications
Cambridge says that mistakes in dividing DNA
for understanding and treating infertility, birth
between daughter cells during meiosis are the
defects and cancer.
leading cause of human birth defects and mis
Getting the Message
carriages. Current estimates are that 10 percent
So, we’ve described DNA — its basic properties
of all embryos have an incorrect chromosome
and how our bodies make more of it. But how
number. Most of these don’t go to full term and
does DNA serve as the language of life? How do
you get a protein from a gene?
In women, the likelihood that chromosomes
won’t be apportioned properly increases with age.
One of every 18 babies born to women over 45
has three copies of chromosome 13, 18 or 21
instead of the normal two, and this improper
balancing can cause trouble. For example, three
copies of chromosome 21 lead to Down
To make her work easier, Amon—like many
other basic scientists —studies yeast cells, which
separate their chromosomes almost exactly the
same way human cells do, except that yeast do it
much faster. A yeast cell copies its DNA and
produces daughter cells in about 11/2 hours,
to a whole day for human cells.
Trisomy, the hallmark of Down syndrome, results
when a baby is born with three copies of chromo
The yeast cells she uses are the same kind
some 21 instead of the usual two.
bakeries use to make bread and breweries use
to make beer!
12 National Institute of General Medical Sciences There are two major steps in making a
You’d think that for a process so essential to
protein. The first is transcription, where the
life, researchers would know a lot about how
information coded in DNA is copied into RNA.
transcription works. While it’s true that the
The RNA nucleotides are complementary to
basics are clear— biologists have been studying
those on the DNA: a C on the RNA strand
gene transcribing by RNA polymerases since
matches a G on the DNA strand.
these proteins were first discovered in 1960—
The only difference is that RNA pairs a
some of the details are actually still murky.
nucleotide called uracil (U), instead of a T, with
an A on the DNA.
A protein machine called RNA polymerase
reads the DNA and makes the RNA copy. This
copy is called messenger RNA, or mRNA, because
it delivers the gene’s message to the protein
At this point you may be wondering why all
of the cells in the human body aren’t exactly
alike, since they all contain the same DNA. What
makes a liver cell different from a brain cell? How
do the cells in the heart make the organ contract,
but those in skin allow us to sweat?
Cells can look and act differently, and do
entirely different jobs, because each cell “turns
on,” or expresses, only the genes appropriate for
what it needs to do.
That’s because RNA polymerase does not
work alone, but rather functions with the aid of
many helper proteins. While the core part of
RNA polymerase is the same in all cells, the
helpers vary in different cell types throughout
. RNA polymerase transcribes DNA to
make messenger RNA (mRNA).
The New Genetics I How Genes Work 13
The biggest obstacle to learning more
But our understanding is improving fast,
has been a lack of tools. Until fairly recently,
thanks to spectacular technological advances.
researchers were unable to get a picture at the
We have new Xray pictures that are far more
atomic level of the giant RNA polymerase prosophisticated than those that revealed the structure tein assemblies inside cells to understand how
of DNA. Roger Kornberg of Stanford University in
the many pieces of this amazing, living machine
California used such methods to determine the
do what they do, and do it so well.
structure of RNA polymerase. This work earned
. Amino acids link up to
make a protein.
. The mRNA sequence (dark red strand) is com
. On ribosomes, transfer RNA (tRNA) helps
plementary to the DNA sequence (blue strand).
convert mRNA into protein.
14 National Institute of General Medical Sciences him the 2006 Nobel
Nature’s CutandPaste Job
Prize in chemistry. In
Several types of RNA play key roles in making
addition, very powerful
a protein. The gene transcript (the mRNA)
microscopes and other
transfers information from DNA in the nucleus to
tools that allow us to
the ribosomes that make protein. Ribosomal RNA
watch one molecule
forms about 60 percent of the ribosomes. Lastly,
at a time provide a
transfer RNA carries amino acids to the ribonew look at RNA polysomes. As you can see, all three types of cellular merase while it’s at work
RNAs come together to produce new proteins.
reading DNA and pro
But the journey from gene to protein isn’t
quite as simple as we’ve just made it out to be.
For example, Steven
After transcription, several things need to hap
Block, also of Stanford,
pen to mRNA before a protein can be made. For
has used a physics techexample, the genetic material of humans and nique called optical
other eukaryotes (organisms that have a
trapping to track RNA
nucleus) includes a lot of DNA that doesn’t
polymerase as it inches
encode proteins. Some of this DNA is stuck right
. RNA polymerase (green) and one end of a DNA
strand (blue) are attached to clear beads pinned
along DNA. Block and
in the middle of genes.
down in two optical traps. As RNA polymerase
moves along the DNA, it creates an RNA copy of
his team performed
To distinguish the two types of DNA, sciena gene, shown here as a pink strand.
this work by designing
tists call the coding sequences of genes exons and STEVEN BLOCK
a specialized microscope
the pieces in between introns (for intervening
sensitive enough to watch the realtime motion of
a single polymerase traveling down a gene on
If RNA polymerase were to transcribe DNA
from the start of an introncontaining gene to
The researchers discovered that molecules of
the end, the RNA would be complementary to
RNA polymerase behave like batterypowered
the introns as well as the exons.
spiders as they crawl along the DNA ladder,
To get an mRNA molecule that yields a workadding nucleotides one at a time to the growing ing protein, the cell needs to trim out the intron
RNA strand. The enzyme works much like a
sections and then stitch only the exon pieces
motor, Block believes, powered by energy released
together (see drawing, page 15). This process is
during the chemical synthesis of RNA.
called RNA splicing.
The New Genetics I How Genes Work 15
Genes are often interrupted
by stretches of DNA
(introns, blue) that do not
contain instructions for
making a protein. The DNA
segments that do contain
protein making instructions
are known as exons (green).
Arranging exons in different
patterns, called alternative
splicing, enables cells to
make different proteins
from a single gene.
16 National Institute of General Medical Sciences Splicing has to be extremely accurate. An
By cutting and pasting the exons in different
error in the splicing process, even one that results
patterns, which scientists call alternative splicing,
in the deletion of just one nucleotide in an exon
a cell can create different proteins from a single
or the addition of just one nucleotide in an
gene. Alternative splicing is one of the reasons
intron, will throw the whole sequence out of
why human cells, which have about 20,000
alignment. The result is usually an abnormal
genes, can make hundreds of thousands of
protein—or no protein at all. One form of
Alzheimer’s disease, for example, is caused by
All Together Now
this kind of splicing error.
Until recently, researchers looked at genes, and
Molecular biologist Christine Guthrie of the
the proteins they encode, one at a time. Now, they
University of California, San Francisco, wants
can look at how large numbers of genes and proto understand more fully the mechanism for teins act, as well as how they interact. This gives
removing intron RNA and find out how it stays
them a much better picture of what goes on in a
She uses yeast cells for these experiments.
Already, scientists can identify all of the genes
Just like human DNA, yeast DNA has introns,
that are transcribed in a cell — or in an organ, like
but they are fewer and simpler in structure and
the heart. And although researchers can’t tell you,
are therefore easier to study. Guthrie can identify
right now, what’s going on in every cell of your
which genes are required for splicing by finding
body while you read a book or walk down the
abnormal yeast cells that mangle splicing.
street, they can do this sort of “wholebody” scan
So why do introns exist, if they’re just going to
for simpler, singlecelled organisms like yeast.
be chopped out? Without introns, cells wouldn’t
Using a technique called genomewide
need to go through the splicing process and keep
location analysis, Richard Young of the
monitoring it to be sure it’s working right.
Massachusetts Institute of Technology unraveled
As it turns out, splicing also makes it possible
a “regulatory code” of living yeast cells, which
for cells to create more proteins.
have more than 6,000 genes in their genome.
Think about all the exons in a gene. If a cell
Young’s technique enabled him to determine
stitches together exons 1, 2 and 4, leaving out
the exact places where RNA polymerase’s helper
exon 3, the mRNA will specify the production
proteins sit on DNA and tell RNA polymerase
of a particular protein. But instead, if the cell
to begin transcribing a gene.
stitches together exons 1, 2 and 3, this time leav
Since he did the experiment with the yeast
ing out exon 4, then the mRNA will be translated
exposed to a variety of different conditions,
into a different protein (see drawing, page 15).
The New Genetics I How Genes Work 17
GENETICS AND YOU: Nursery Genetics W hile most genetic research Newborn screening is governed by uses lab organisms, test
individual states. This means that the
tubes and petri dishes,
state in which a baby
the results have real consequences for
is born determines the
people. Your first encounter with
genetic conditions for
genetic analysis probably happened
which he or she will be
shortly after you were born, when a
doctor or nurse took a drop of blood
states test for between
from the heel of your tiny foot.
28 and 54 conditions. All states test
Lab tests performed with that single
drop of blood can diagnose certain rare
Although expanded screening for
genetic disorders as well as metabolic
genetic diseases in newborns is advoproblems like phenylketonuria (PKU).
cated by some, others question the
Screening newborns in this way
value of screening for conditions that
began in the 1960s in Massachusetts
are currently untreatable. Another
with testing for PKU, a disease affecting
issue is that some children with mild
1 in 14,000 people. PKU is caused by an
versions of certain genetic diseases
enzyme that doesn’t work properly due
may be treated needlessly.
to a genetic muta
In 2006, the Advisory Committee
tion. Those born
on Heritable Disorders in Newborns
with this disorder
and Children, which assists the Secretary
of the U.S. Department of Health and
the amino acid
Human Services, recommended a
standard, national set of newborn
which is present
tests for 29 conditions, ranging from
in many foods. Left untreated, PKU can
relatively common hearing problems
lead to mental retardation and neurologto very rare metabolic diseases.
ical damage, but a special diet can
prevent these outcomes. Testing for this
condition has made a huge difference in
18 National Institute of General Medical Sciences Young was able to figure out how transcription
method to scan the entire human genome in
patterns differ when the yeast cell is under stress
small samples of cells taken from the pancreases
(say, in a dry environment) or thriving in a sugaryand livers of people with type 2 diabetes. He rich nutrient solution. Done one gene at a time,
used the results to identify genes that aren’t tranusing methods considered stateoftheart just a scribed correctly in people with the disease.
few years ago, this kind of analysis would have
This information provides researchers with
taken hundreds of years.
an important tool for understanding how dia
After demonstrating that his technique
betes and other diseases are influenced by
worked in yeast, Young then took his research
defective genes. By building models to predict
a step forward. He used a variation of the yeast
how genes respond in diverse situations,
researchers may be able to learn how to stop or
jumpstart genes on demand, change the course
of a disease or prevent it from ever happening.
Found in Translation
After a gene has been read by RNA polymerase
and the RNA is spliced, what happens next in
the journey from gene to protein? The next step
is reading the RNA information and fitting the
building blocks of a protein together. This is
called translation, and its principal actors are
the ribosome and amino acids.
Ribosomes are among the biggest and most
intricate structures in the cell. The ribosomes of
bacteria contain not only huge amounts of RNA,
but also more than 50 different proteins. Human
ribosomes have even more RNA and between 70
and 80 different proteins!
Harry Noller of the University of California,
. A ribosome consists of large and small
Santa Cruz, has found that a ribosome performs
protein subunits with transfer RNAs
nestled in the middle.
several key jobs when it translates the genetic
RIBOSOME STRUCTURE COURTESY OF JAMIE CATE, MARAT YUSUPOV, code of mRNA. As the messenger RNA threads
GULNARA YUSUPOVA, THOMAS EARNEST AND HARRY NOLLER. GRAPHIC
COURTESY OF ALBION BAUCOM, UNIVERSITY OF CALIFORNIA, SANTA CRUZ.
through the ribosome protein machine, the
The New Genetics I How Genes Work 19
ribosome reads the mRNA sequence and helps
recognize and recruit the correct amino acidcarrying transfer RNA to match the mRNA code.
The ribosome also links each additional amino
acid into a growing protein chain (see drawing,
For many years, researchers believed that even
though RNAs formed a part of the ribosome, the
protein portion of the ribosome did all of the
work. Noller thought, instead, that maybe RNA,
. Some firstaid ointments contain the antibiotic neomycin, not proteins, performed the ribosome’s job. His
which treats infections by attacking ribosomes in bacteria.
idea was not popular at first, because at that time
it was thought that RNA could not perform such
But which ribosomal RNAs are doing the work?
Some time later, however, the consensus
Most scientists assumed that RNA nucleotides
changed. Sidney Altman of Yale University in
buried deep within the ribosome complex—the
New Haven, Connecticut, and Thomas Cech,
ones that have the same sequence in every species
who was then at the University of Colorado in
from bacteria to people—were the important
Boulder, each discovered that RNA can perform
ones for piecing the growing protein together.
work as complex as that done by protein enzymes.
However, recent research by Rachel Green,
Their “RNAasanenzyme” discovery turned the
who worked with Noller before moving
research world on its head and earned Cech and
to Johns Hopkins University in Baltimore,
Altman the 1989 Nobel Prize in chemistry.
Maryland, showed that this is not the case.
Noller and other researchers have continued
Green discovered that those RNA nucleotides
the painstaking work of understanding riboare not needed for assembling a protein. Instead, somes. In 1999, he showed how different parts
she found, the nucleotides do something else
of a bacterial ribosome interact with one
entirely: They help the growing protein slip off
another and how the ribosome interacts with
the ribosome once it’s finished.
molecules involved in protein synthesis.
Noller, Green and hundreds of other scientists
These studies provided near proof that the
work with the ribosomes of bacteria. Why should
fundamental mechanism of translation is
you care about how bacteria create proteins from
performed by RNA, not by the proteins of
20 National Institute of General Medical Sciences One reason is that this knowledge is impor
An Interesting Development
tant for learning how to disrupt the actions of
In the human body, one of the most important
diseasecausing microorganisms. For example,
jobs for proteins is to control how embryos
antibiotics like erythromycin and neomycin work
develop. Scientists discovered a hugely important
by attacking the ribosomes of bacteria, which are
set of proteins involved in development by studydifferent enough from human ribosomes that our ing mutations that cause bizarre malformations
cells are not affected by these drugs.
in fruit flies.
As researchers gain new information about
The most famous such abnormality is a fruit
bacterial translation, the knowledge may lead to
fly with a leg, rather than the usual antenna,
more antibiotics for people.
growing out of its head (see page 21). According
New antibiotics are urgently needed because
to Thomas C. Kaufman of Indiana University
many bacteria have developed resistance to the
in Bloomington, the leg is perfectly normal—it’s
current arsenal. This resistance is sometimes the
just growing in the wrong place.
result of changes in the bacteria’s ribosomal RNA.
In this type of mutation and many others,
It can be difficult to find those small, but critical,
something goes wrong with the genetic program
changes that may lead to resistance, so it is
that directs some of the cells in an embryo to
important to find completely new ways to block
follow developmental pathways, which are
a series of chemical reactions that occur in a
Green is working on that problem too. Her
specific order. In the antennaintoleg problem,
strategy is to make random mutations to the
it is as if the cells growing from the fly’s head,
genes in a bacterium that affect its ribosomes.
which normally would become an antenna,
But what if the mutation disables the ribosome