27Zero to Genetic Engineering Hero - Chapter 1 - Isolating DNA, the Blueprints of Life
Atoms, molecules, and
macromolecules of the cell
DNA is housed inside cells, but what are cells made

atoms: Are you familiar with the periodic table of

book. Take a moment to explore it. The periodic table
is color coded to tell you where each of the elements
is used in cells. Atoms such as carbon (C), hydrogen
(H), oxygen (O), phosphorous (P), nitrogen (N), and
sulfur (S) are brought together by machinery in cells
to form molecules. A molecule is the combination of
two or more atoms that are bound together. Carbon,
hydrogen, oxygen, nitrogen, phosphorous and sulfur
are generally considered organic elements because
they are frequently used by organisms. As you
completed the hands-on DNA extraction, keep in
mind that most of the “cellular stuff” that you manip-
ulated was made of these elements, and in the case of
extracting DNA from cells, DNA is made of CHOPN.
A cell has the necessary machinery to combine atoms
into molecules, and it also has the machinery inside
to combine molecules together to form macromole-
cules. The term macromolecule is used to describe
the four basic components of cells: proteins, lipids,
carbohydrates, and nucleic acids. In Chapter 1, the
-
ribonucleic acid (DNA) in cells.
What would it look like if you were to peek into a cell
to look at the atoms, molecules, and macromolecules?
The inside might look like a ball pit, but rather than
colorful plastic spheres, there is a sea of different
molecules packed together and bumping into one
another (Figure 1-14). Imagine being immersed in the
depths of a ball pit - completely surrounded. If you


would be comparable to other molecules of the cell.
Figure 1-13. Great Dane skeleton (left) compared to a Chi-
huahua skeleton (right), both descendants of Canis Lupus, at
the Museum of Osteology.
Keep in Mind!

facts. You can try to think of CHOPNS as the word
“Choppings.” Imagine chopping up some yummy celery
or carrots into little bits for your soup. Atoms are like
that; the little bits that make up the molecules in cells,
just like celery and carrots make up the soup.
Of particular importance in living organisms are the
organic’ elements CHOPNS; carbon, hydrogen, oxygen,
phosphorous, nitrogen, and sulfur.
Figure 1-12.
its ancestor Teosinte (top) and a hybrid of both (middle).
Photo by John Doebley - http://teosinte.wisc.edu/images.html
Figure 1-14. A ball pit is a good analogy for thinking about
how the inside of cells are packed with molecules.
Book _genetic engineering hero-AUG2021.indb 27Book _genetic engineering hero-AUG2021.indb 27 8/18/21 12:03 PM8/18/21 12:03 PM
28 Zero to Genetic Engineering Hero - Chapter 1 - Isolating DNA, the Blueprints of Life

small, such as oxygen gas (O
2
) with only two atoms, to
water (H
2
O) with three atoms, to DNA which is by far
the most enormous at millions or billions of atoms. In
the DNA extraction exercise, you saw with your own
eyes how much DNA was in the strawberry cells - that
glob of DNA was made of trillions of atoms. And the
other macromolecules, such as the proteins, lipids,
and carbohydrates bound up by the surfactants into
micelles, were made up of trillions more.
DNA: The blueprints of living cells
A blueprint is used for storing information about the
construction and maintenance of a factory and the
processes inside.
Blueprints for the building may have information
about the structural components (e.g. brick outer shell
supported by iron beams), the ventilation systems (e.g.
made of aluminum ducting), the complex electrical
e.g. different voltages, wires, and loca-
tion of the outlets). Blueprints can also determine how
a building is built. Is a crane needed? If so, scaffolding
may be erected to accommodate for this.

inside, how it is positioned, and the speed at which it
operates. A lot of equipment and infrastructure is
permanently connected to the factory. In this case,
the components, machines and the factory building
itself meld to become one. In other words, a factory is
not just a building, but is the building, equipment,
and even the people inside, turning raw materials
into end products.
Why are we talking about factories? Factories as we
know them are analogous to living cellsexcept they
are much larger and made of different materials. The

factory are comparable to the blueprints of living
cells. In the case of living cells, however, there is not
a miniature piece of blue paper rolled up in every cell.
There is a microscopic chemical string, the DNA.
Unlike a factory blueprint that you can see with your
eyes, hold in your hands, and is written in a language
that is well understood, the blueprint of a living cell,
DNA, is a microscopic “chemical string” of nucleotide
building blocks. This string has a distinct “language”
that all living cells know how to read and write. Only
-
lind Franklin, and Maurice Wilkins discovered the
structure of DNA have we begun to understand it and
its language. Here is some of what we know:
DNA is made of four chemical building blocks called
nucleotides that are attached to one another in vari-
ous orders to form a “string” of the nucleotides that
can be thousands to millions of nucleotides long.
Each nucleotide is made of CHOPN, and each nucleo-
tide is made up of three “sub-molecules” called a
phosphate, a nitrogenous base, and a deoxyribose
sugar (Figure 1-16). Have a look at Figure 1-16, do you
see the CHOPN chemical elements?
Phosphate is a molecule with a phosphorus atom
bound to four oxygen atoms. Phosphate is a critical
component of the “sugar-phosphate” backbone of
DNA (Figure 1-17). The phosphate group is very
negatively charged and is what gives DNA an overall
negative charge. As you saw in Chapter 1’s exercise,
the negative charge of DNA is an important chemi-
cal characteristic that you took advantage of to
extract DNA from cells using chemistry.
Nitrogenous bases are the variable part of a nucle-
otide. While every nucleotide has the same
phosphate
backbone, there are four different nitrogenous
bases in DNA - Guanine, Thymine, Adenine, and
C
nitrogenous bases? If you have trouble, try the What
is DNA? application mentioned in the hands-on
exercise. The nitrogenous base is the part of the
nucleotide molecules that is the information that
the cell machinery “reads”.
Deoxyribose is a sugar ring that is the “D” in DNA.
Deoxyribose connects to both the nitrogenous base
and the phosphate (Figure 1-16). When multiple
nucleotides are connected, as seen in Figure 1-16,
you’ll see that the deoxyribose also connects to the
phosphate of the next nucleotide. The deoxyribose
and the phosphate together form the “sugar-phos-
phate” backbone of DNA (Figure 1-17).
~3,000 nt/bp
S
E
L
E
C
T
I
O
N
/
G
E
N
E
T
R
A
I
T
/
G
E
N
E
O
R
I
Figure 1-15. Comparing factory blueprints (left) to the blue-
prints of a living cell, DNA (right).
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29Zero to Genetic Engineering Hero - Chapter 1 - Isolating DNA, the Blueprints of Life

of their nitrogenous base names. Because four differ-
ent nitrogenous bases can be attached to the
deoxyribose ring, four different possible nucleotides
make up DNA: A for adenine, T for thymine, C for cyto-
sine and G for g
nucleotide chains side-by-side in Figure 1-17, and
both have each of the four nucleotides.
During regular cell activity, millions of each of the four
nucleotides are produced by the cell. The nucleotides
in the cell can be collected by a cell machine called
DNA polymerase, which strings them together like
pearls in a necklace. It is the order of the nucleotides
…ATGGCGGTTACCwhich we call the DNA sequence
that the cell machinery reads and understands.
As you see in Figure 1-17, the sugar-phosphate back-
bones are on the outside of the molecule, and the
nitrogenous bases are buried inside. If you imagine
DNA to be a ladder, the sugar-phosphate would be the
outside of the ladder, and the nitrogenous bases would
be the ladder rungs. This means that the “information”
that the cells machinery reads is in the rungs of the
ladder. If you look at Strand 1 in Figure 1-17, reading

end, the DNA sequence is GCAT.
When two strands of DNA come together, they form a
three-dimensional structure known as the double
helix. Looking down at the structure from the top, it
looks like a spiral staircase (Figure 1-19). The blue-
gray region in the center of the illustration shows the
nitrogenous bases, the As, T’s, C’s and Gs that form
the information layer of the DNA blueprint. These are
held in place by the outer orange-red-gray region of
the negatively-charged sugar-phosphate backbone.
The sugar-phosphate backbone has two critical func-
tions: i) to maintain structure and hold the nucleotide
bases in place; ii) to selectively attract cellular machin-
ery called proteins so that the cell can “read” the DNA.
In simplest terms, you can think of the sugar-phos-
phate backbone as the paper of a blueprint, and the
nitrogenous bases as the words (information) written
on the blueprint that can be understood.
A cool property of DNA is that the two strands of a
double helix are only loosely connected by hydrogen
bonds (which you will learn more about in Chapter 6).
These loose bonds mean that the two strands can

-


In DNA, the chemical bonds in the sugar-phosphate
backbone are very strong, but the bonds between two
strands are relatively weak (Figure 1-17; dashed lines).

DNA functions. The cellular machinery can bind to the
sugar-phosphate backbone and pull the double helix
  

the information.

together? Yes! One fundamental rule was discovered
by a famous scientist called Erwin Chargaff. Char-
gaffs rule states that: Only an “A” in one strand can bind
to a “T” in the other, and only a “C” in one strand can bind
to a “G” in the other: the nitrogenous bases of As and
T’s complement each other and the same with C’s and
Gs. In Figure 1-17, you’ll see Chargaffs Rule in action.
Only when two strands have “complementary” nucle-
otides can they wind up together! As you learn more
about the nuts and bolts of genetic engineering in
later chapters, this will become much more evident.
Anatomy of a DNA Nucleotide
The Building Blocks of Nucleic Acids
A
dAdenosine
Full nucleotide name
d: short for deoxy
Single letter abbreviation
Nitrogenous
base (here,
adenine is
shown)
Deoxyribose
Phosphate
O
H
C
CH
2
O
O
C
P
N
C
C
O
NC
C
C C
N
H H
N
N
C
O
-O
H
1
23
4
5
Figure 1-16. The building blocks of DNA, nucleotides, have
important characteristics. A conserved phosphate, deoxyri-
bose sugar, and the variable nitrogenous base.
Book _genetic engineering hero-AUG2021.indb 29Book _genetic engineering hero-AUG2021.indb 29 8/18/21 12:03 PM8/18/21 12:03 PM
30 Zero to Genetic Engineering Hero - Chapter 1 - Isolating DNA, the Blueprints of Life
O
O
C
CH
2
O
O
C
P
N
O
C
C
NN
C
C C
C
H
H
-O
H
O
C
CH
2
O
O
-O
O
C
P
O
C
C
N
C
C
N
H
N
H
H
C
C
N
N
C
H
O
C
CH
2
O
O
C
P
N
C
C
O
NC
C
C C
N
H
H
N
N
C
O
-O
H
O
C
CH
2
O
O
C
P
O
C
C
O
NN
C
C C
C
H
-O
H
C
H
H
H
O
H
O
O
C
CH
2
O
O
C
P
N
O
C
C
NN
C
C C
C
H
H
-O
H
O
C
CH
2
O
O
-O
O
C
P
O
C
C
N
C
C
N
H
N
H
H
C
C
N
N
C
H
O
C
CH
2
O
O
C
P
N
C
C
O
NC
C
C C
N
H
H
N
N
C
O
-O
H
O
C
CH
2
O
O
C
P
O
C
C
O
NN
C
C C
C
H
-O
H
C
H
H
H
O
H
Nucleotide
abbreviation
Sugar-Phosphate
backbone
Nucleotide base
Hydrogen
bonding
Nucleotides
A
dAdenosine
C
dCytidine
T
dThymidine
G
dGuanosine
A
dAdenosine
T
dThymidine
G
dGuanosine
C
dCytidine
5’ Phosphate end
3’ OH end
5’ Phosphate end
3’ OH end
Figure 1-17.

bonding occurs between the nitrogenous bases alone, not via the sugar-phosphate backbone. You will learn about bonding in
Chapter 6.
Strand 1 Strand 2
Book _genetic engineering hero-AUG2021.indb 30Book _genetic engineering hero-AUG2021.indb 30 8/18/21 12:03 PM8/18/21 12:03 PM
31Zero to Genetic Engineering Hero - Chapter 1 - Isolating DNA, the Blueprints of Life
A
dAdenosine
O
H
C
CH
2
O
O
C
P
N
C
C
O
NC
C
C C
N
H H
T
dThymidine
O
H
C
CH
2
O
O
C
P
O
C
C
O
NN
C
C C
C
H
G
d
Guanosine
O
H
C
CH
2
O
O
-O
O
C
P
O
C
C
O
N
C
C
N
H
N
H
H
C
dCytidine
O
H
C
CH
2
O
O
C
P
N
O
C
C
O
NN
C
C C
C
H
H
N
N
C
C
C
N
N
C
O
-O
O
-O
O
-O
H
H
H
H
C
H
H
H
O
Figure 1-18. The four nucleotide building blocks of DNA are called deoxyguanosine (dG), deoxycytidine (dC), deoxyadenosine (dA),
and deoxythymidine (dT). For simplicity, they are often referred to by their nitrogenous base names: guanine (G), cytosine (C), ade-
nine (A), and thymine (T). A small d is an abbreviation for ‘deoxy.’ You’ll learn more about this when you discover RNA in Chapter 4.
Top through view of a double stranded helix Side prole view of a double stranded helix
Sugar - Phosphate
backbone
Sugar - Phosphate
backbone
Nucleotide
bases
Sugar - Phosphate
backbone
Sugar - Phosphate
backbone
Nucleotide
bases
Sugar - Phosphate
backbone
Nucleotide bases
Figure 1-19. The DNA helix is a three-dimensional structure that forms when two strands of DNA bind together using Chargaffs
Rule. The blue-gray region indicates the nitrogenous bases, and the red-orange-gray region indicates the negatively charged sug-
ar-phosphate backbone.
Book _genetic engineering hero-AUG2021.indb 31Book _genetic engineering hero-AUG2021.indb 31 8/18/21 12:03 PM8/18/21 12:03 PM
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