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Deep in the DNA
Deep in the DNA
Each day in the United States, on average 22 people die
while waiting for an organ transplant. Over 113,000 men,
women, and children are currently on the national
transplant waiting list, each hoping their name is called
before it's too late.
Researchers have explored many ways to grow and store
organs for transplantation-from freezing them to building
them from scratch-but one of the most promising, if you
can look past the mud and flies, is pigs. Our porcine friends
have long been considered an excellent potential source of
organs because their organs-including the heart, liver, and
kidneys-are relatively close in size to human organs and
because pigs and humans have similar anatomies (Figure
9.2). In addition, pigs are an easier sell to the public: people
tend to prefer the idea of transplants from pigs over
transplants from mammals more closely related to us, such
as baboons. If we were able to transplant organs from
nonhuman animals into humans, a process called
xenotransplantation, healthy organs could be available in
essentially limitless supply.
Kidney Pancreas
Liver
Heart Lung
Figure 9.2
Pig organs and human organs are remarkably similar in
size
For a nonhuman-to-human organ transplant to succeed, the
nonhuman organ must fit into the space where the human organ
was removed. Organs that are too big will not fit. Organs that are
too small will not function at the level necessary to sustain life.
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Deep in the DNA
Yet there has been a barrier to harvesting pig organs for
humans: the pig genome is dotted with DNA from a family
of viruses called porcine endogenous retroviruses, or
PERVS. Because of the presence of this viral DNA in the pig
genome, pig cells produce and release PERVS-and two of
the three subtypes of PERVS can infect human cells, making
it risky to transplant pig organs into people for fear of
making the recipients sick.
After pigs acquired the viruses, PERV DNA slipped easily
into the pig genome because it has the same structure as
pig DNA. In fact, all living things share the same DNA
structure, and species often share and swap DNA with each
other. As discussed in Chapters 3-4, DNA is built from two
parallel strands of repeating units called nucleotides. Each
nucleotide is composed of the sugar deoxyribose, a
phosphate group, and one of four bases: adenine, cytosine,
guanine, or thymine. We identify nucleotides by their bases,
using "adenine nucleotide" as shorthand for "nucleotide
with an adenine base."
The nucleotides of a single strand are connected by
covalent bonds between the phosphate group of one
nucleotide and the sugar of the next nucleotide. The two
DNA strands are connected by hydrogen bonds linking the
bases on one strand to the bases on the other, like the rungs
that connect the two sides of a ladder (Figure 9.3). Covalent
bonds are strong, which is important in maintaining the
specific order of the nucleotides. The weaker hydrogen
bonds allow the two DNA strands to be pulled apart for
replication.
A pairs only with T
The nucleotides
in one strand
are paired with
the nucleotides
in the
complementary
strand.
C pairs only with G.
The two strands
of DNA are held
together by
hydrogen
bonds (dotted
lines) between
the bases.
Nucleotides
are linked
together by
covalent
bonds to form
one strand of
DNA.
Q1: Name two base pairs.
SHOW ANSWER
0000
SHOW ANSWER
Phosphate
Sugar (deoxyribose)
Sugar-phosphate Base
Nucleotide
Nucleotide bases:
Adenine
Figure 9.3
A molecule of DNA consists of two complementary strands of
nucleotides that are twisted into a spiral around an imaginary
axis, rather like the winding of a spiral staircase.
Thymine
Guanine Cytosine
Q2: Why is the DNA structure referred to as a "ladder"?
What part of the DNA represents the rungs of the ladder?
What part represents the sides?
Q3: Is the hydrogen bond that holds the base pairs together
a strong or weak chemical bond? Why is that important?
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SHOW ANSWER
Deep in the DNA
You can also see Appendix A for answers to the figure questions.
The term base pair, or nucleotide pair, refers to two
nucleotides held together by bonds between their bases;
that is, a base pair corresponds to one rung of the DNA
ladder. The ladder twists into a spiral called a double helix
(Figure 9.4). Within the long, winding double helix of the pig
genome, short sections of DNA from PERVS are scattered
about. These PERV sections are made up of the same four
nucleotides as the rest of the DNA, but they encode
information for viral proteins instead of pig proteins.
Figure 9.4
What DNA actually looks like
In November 2012, Italian researchers used an electron
microscope to directly visualize DNA for the first time. This is the
single thread of double-stranded DNA that they saw.
Nucleotides do not form base pairs willy-nilly. As shown
in Figure 9.3, the adenine (A) nucleotide on one strand can
pair only with thymine (T) on the other strand; cytosine (C)
on one strand can pair only with guanine (G) on the other
strand. These base-pairing rules, which provide
complementary base-pairing between two nucleic acid
strands, have an important consequence: when the
sequence of nucleotides on one strand of the DNA molecule
is known, the sequence of nucleotides on the other,
complementary strand of the molecule is automatically
known as well. The fact that A can pair only with T and that
C can pair only with G allows the original strands to serve
as "template strands" on which new strands can be built
through complementary base-pairing. (In Chapter 10, we
delve more deeply into building new DNA strands, including
how RNA can pair with DNA, which CRISPR takes advantage
of.)
Still, the four nucleotides can be arranged in any order
along a single strand of DNA, and each DNA strand is
composed of millions of these nucleotides, so a tremendous
amount of information can be stored in a DNA sequence
and in a genome. The genome of the domestic pig, for
example, has about 3 billion base pairs, the human genome
has about 3.2 billion base pairs, a tomato has only about 900
million base pairs, and the bacterium Escherichia coli (better
known as E. coli) has a measly 4.6 million. The sequence of
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Deep in the DNA
nucleotides in DNA differs among species and among
individuals within a species, and these differences in
genotype can result in different phenotypes (Figure 9.5).
MIN
G A C
SHOW ANSWER
A
Human A
Figure 9.5
The sequence of bases in DNA differs among species and
among individuals within a species
The sequence of bases in a hypothetical gene is compared for
two humans (A and B) and a pig. Base pairs highlighted in blue
are variant; that is, they differ between the genes of persons A
and B and between the same genes in humans and pigs.
SHOW ANSWER
Human B
Q1: If all genes are composed of just four nucleotides, how
can different genes carry different types of information?
Pig
SHOW ANSWER
Q2: Would you expect to see more variation in the
sequence of DNA bases between two members of the
same species (such as humans) or between two individuals
of different species (for example, humans and pigs)?
Explain your reasoning.
Q3: Do different alleles of a gene have the same DNA
sequence or different DNA sequences?
You can also see Appendix A for answers to the figure questions.
In the mid-1990s, scientists became very excited about
the idea of using pig organs in humans, but testing stalled
because of the fear that humans would become infected
with PERVS. Just breeding pigs in sterile conditions can't get
rid of the virus; it's integrated right there in the double
helix. The Harvard Medical School team believed CRISPR
might be able to solve that problem by inactivating the
PERV DNA in pig cells once and for all.
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