Wonders of DNA

CONTENT

1. What is DNA?

2. History of DNA

3. DNA Structure

4. Differences and Similarities between DNA and RNA

5. DNA Packaging

6. DNA Replication

7. DNA Comparison and DNA Fingerprinting

8. Is DNA Important?

9. Conclusion
 What is DNA?

Simply put, DNA (Deoxyribonucleic Acid) is a string of nitrogenous bases (Adenine,

Thymine, Guanine, and Cytosine) repeated over and over, and arranged in a seemingly
random fashion. Here the genetic code is contained. These bases are connected to each
other through chemical bonds. Two complementary strands of DNA are bonded to each
other, and are twisted in a helical structure. This extremely long double-stranded twisted
string has parts that code for everything in all organisms. Different parts are under different
selection pressures.

Below we will outline the history, structure of DNA, the differences and similarities
between DNA and RNA. After this, we will then dive into why DNA is so important. Given
how important this structure is, we will also talk about how it is replicated (DNA replication),
packaged, and how these can be exploited or used for DNA fingerprinting.

History of DNA

The discovery of the structure of DNA opened many avenues in the field of biology.
In 1962, Watson, Crick, and Wilkins obtained a Nobel Peace Prize for describing it. However,
its existence was known of before that. In 1866, Gregor Mendel first hypothesized the
existence of inherited entities, now known as genes. Later on (1869), Friedrich Miescher
noted an acidic substance in the cell’s nuclei; this substance was referred to as nuclein (we
now know this as DNA). Rosalind Franklin captured the famous X-Ray imagery clearly
showing its double helical nature. It is her work together with that of the above-mentioned
Nobel Laureates that gave us the gold mine (DNA) that has led to advances in all fields of
biology; most notably, medicine.

This part of the DNA story is a lot more complex than this, but we will end here for
the purpose of this lesson.

DNA Structure

DNA is a nucleic acid, hinted at in the name. Nucleic acids are the building blocks of
all living organisms. Nucleotides simply refer to nitrogenous bases, pentose sugar together
with the phosphate backbone. Nucleotides are adjacently strung together through a
phosphate backbone and are held together with their complements through hydrogen
bonds. The number of bonds holding nucleotides from the complementary strands depends
on the type of nitrogenous base the nucleotide contains.

Figure 1: The chemical assembly of the three parts

of the nucleotide (in this case adenine), the
phosphate (blue box), nitrogenous base (red box)
and the pentose sugar

Image Source: Wikimedia Commons

A nitrogenous base is a molecule with nitrogen that possesses the chemical properties
of a base. These are crucial to the DNA as they define the genetic code (they are the code!).
The pentose sugar connects the nitrogenous base to the phosphate backbone. There are four
kinds of nitrogenous bases; namely, thymine (T), cytosine (C), adenine (A) and guanine (G).
Guanine and adenine are purines while thymine and cytosine are pyrimidines. Purines
have two rings (see adenine on figure 2) while pyrimidines have one ring. For the structure
of the DNA to be able to twist and be packaged accordingly without bulging and the opposite
bases to be able to pair up, a purine has to fit in a pyrimidine. To this end, the purine guanine
pairs with the pyrimidine cytosine and the purine adenine pairs with the pyrimidine thymine.
Figure 2: The chemical structure of nucleotides and how they bond with their
complements. Image Source: Wikimedia Commons
 Differences and Similarities between DNA and RNA

Both molecules are nucleic acids made up of nucleotides, supported by a phosphate

backbone. They are both major players in the central dogma. RNA is transcribed from the
DNA to make proteins. DNA carries all the information needed for DNA replication and
transfer new information to new cells.

They are involved in the maintenance, replication, and expression of hereditary

information. DNA holds the key to heredity. RNA helps DNA unlock this code and show us
what this code is capable of achieving. Together these molecules ensure that the DNA is
replicated, the code is translated, expressed and that things go where they should go.

DNA and RNA work hand in hand in biology. It is rare that one can speak of the one
without bringing up the other. Simply put, they are connected by the central dogma. The
central dogma is the process of DNA transcription and translation for the purpose of protein
synthesis which then perform a multitude of tasks in organisms. Different types of proteins
guide the gene expression. Therefore, even though the DNA is the same throughout-
different things happen at different part of the body. In addition to this, it also tells stem
cells what to differentiate to. This is due to strict regulatory mechanisms in place to control
gene expression.

Both DNA and RNA have a negative backbone (because of the phosphate group).
They both have four nucleotides each, three of which they share (Guanine, Cytosine, and
Adenine); with one significant difference, DNA has Thymine while RNA has Uracil. DNA is
double-stranded while RNA is single-stranded. Last but not least, DNA is found in the
nucleus while RNA resides both in the nucleus and the cytoplasm. DNA is long-lived while
RNA is regenerated with each reaction.

They are both central to cell function.

 DNA Packaging

How does DNA fit into the cell? Consider this; each and every one of your cells
contains approximately 6 billion base pairs of DNA, with each base pair being 0.34
nanometers long. This works out to about 2 meters of DNA per diploid cell! If the DNA
sequence is so long how does the nucleus manage to house the DNA and many other
components necessary for the functioning of the cell? The answer is very simple, through
condensing and packaging.

DNA is packaged with the help of histone proteins. Histones are small proteins with
basic, positively charged amino acids; namely, arginine and lysine. They bind and neutralize
the negatively charged DNA (because of the negatively charged phosphate backbone). It
takes five types of histones to package DNA; H1, H2A, H2B, H3, and H4. Core histones
(H2A, H2B, H3, and H4) with DNA coiled around them are referred to as nucleosomes. It
takes two of each of the core histones to make up a nucleosome. Per nucleosome an H1
histone sits outside the coil holding the nucleosome intact. The nucleosome together with
histone H1 are collectively referred to as chromatosome. The nucleosomes are condensed to
fibers called chromatin. Bigger loops of tightly packed chromatin then make chromosomes.

Figure 3: Each of the steps

involved in DNA packaging from
the ladder phase through to the
super coiled stage of hi stone
complexes arranged into
chromosomes. Image
Source: Wikimedia Commons
 Keeping DNA in a coiled and inaccessible state ensures DNA safety. As you can
imagine, with this much coiling, twisting and packing the DNA is not accessible for
transcription and/ or replication. This becomes redundant if the DNA cannot perform its
functions. For DNA to perform its functions it needs to be unpacked and made accessible
again. It is in this state that DNA can be replicated in order to, amongst other things;
accommodate organism’s growth and maturity through cell division facilitated by DNA
replication to ensure there is sufficient DNA in every cell.

DNA Replication

To understand DNA replication you will need to keep the following in mind:

– Replication duplicates the genetic information; this means you end up with a collection of
identical DNA strands.

– The rules of DNA replication (A to T; G to C) govern replication.

– Each of the two strands DNA serves as a template of the new strand.

-DNA replication is essential for cell division.

Figure 4: The addition of nucleotides to the exposed

hydroxyl group. Image Source: Wikimedia Commons
 DNA replication takes place in 5’®3’ direction. This means that bases will be added
from left to right direction. The template strand will guide this process by telling the new
strand which base comes next, this will go on until the new strand is complete and the DNA
will once again be double-stranded. Both strands of the old DNA will serve as templates of
two new strands. This means that at the end there will be two double-stranded DNAs,
identical to each other. This way once cell division occurs, the new cells will contain identical
information as the rest of the body. A slew of proteins oversee the whole process make sure
things happen at the right time and in the right way.

Figure 5: DNA replication from both the leading and the lagging strand. Image
Source: Wikimedia Commons

Due to the complementary nature of DNA, one strand is in the 5’®3’ direction while
the other is in the 3’®5’ direction. The fore is referred to as the lagging strand while the
latter is called the leading strand.

In preparation for DNA replication, the double-strand unwinds and separate to form
replication forks. Each template strand attracts the complements to the now exposed bases;
this happens in a stepwise fashion. The back-bone solidifies and the DNA rewinds. This is a
very simplified version of the process. What follows is the detailed version with the enzymes
involved to guide the process.
 An enzyme called helicase unwinds the template strands. The single strand binding
proteins then stabilize the template strands in preparation for the replication, it holds it
open until the end of the replication process. DNA polymerase III synthesizes nucleotides
onto the leading end in the 5’®3′ direction.

The replication directed by the lagging strand, however, is a little more complicated.
Helicase can only synthesize in the 5’®3′ direction, this poses a problem where the only
available direction is 3’®5’. To get around this, Okazaki fragments are synthesized.
Primase, as the name suggests, primes the synthesis of the new strand through
synthesizing RNA primers to direct the addition of Okazaki fragments. Okazaki fragments
are added onto the lagging strand by DNA ligase bonding the 3’ end to the 5’ of the
previous fragment. The primers that prime the addition of the Okazaki fragments are then
removed by DNA polymerase I and replaced by DNA bases. At the end of the process after
the removal of the last primer there is an exposed 3’ end. DNA polymerase III completes
the synthesis of the new strand, by adding DNA nucleotides at the end of the new strand.
Nuclease provides proofreading services, correcting mistakes made during replication. As
you can imagine, there will be a very tight coil at the end of the replication fork.
Topoisomerase fixes this problem by making a small nick that releases the tension build up.

DNA Comparison and DNA Fingerprinting

DNA information has been used in comparative studies in order to understand not
just where we stand as a species in the animal kingdom but where other species fit and how
their genetic make-up influences their way of living. DNA fingerprinting, also called DNA
profiling, refers to a technique of using a collection of individual specific regions of their
genome. This is based on the idea that different combinations of various regions of the
genome are very unlikely to be shared across individual. So, for example even though some
of these sections can be shared between family members it is highly unlikely that they
would all be identical between family members.

Different parts of the DNA code are under stricter selection pressures. This fact is
one of the most exploited properties of the genome when studying organisms at different
levels (e.g. population level, species level, genus level, etc.). Gene regions such as those
coding for the internal transcriber region of the ribosome are under somewhat strict
controls, and these evolve relatively slow. These, can, therefore, be used to study variations
at the species level (species level marker). Other markers are under very little to no
selection (neutral selection) and therefore evolve more freely, for example, simple sequence
repeats such as micro satellites. These are more informative and can be used to study
population dynamics. Some areas evolve so fast that they can be used to identify and
different between individuals in a population to differentiating between individuals born of
the same parents.

Figure 6: Chromatograph of a partial ITS DNA profile of an Ophiostomasplendens (Protea-

associated fungus)

Using regions in the nuclear DNA to identify individuals, species or higher taxa is
what we refer to as DNA bar coding. To study population dynamics markers such micro-
satellites prove useful as their polymorphic profile can tell us a lot about how often intra and
inter-breeding occur within and across populations. It can also give clues to infer modes of
dispersal. To study evolutionary processes and phylogenetic relationships slow evolving
markers such as mitochondrial DNA can be used. These can tell us where species sit in the
bigger picture.

There are a large variety of fields in biology that exist because of the ability to study
and manipulate the DNA code. These include fields such as genetic engineering; this is how
you can enjoy summer fruits in winter. Other fields include gene therapy; here biologists
use the knowledge of the genome to manipulate specific parts of the genome to remove
lethal variants of some genes. The availability of techniques such as DNA fingerprinting also
helps to better understand genetic diseases, and with the help of research such as that into
CRISPR-CAS9, hopefully, enable us to cure diseases such as cancer.

Is DNA Important?

The simple answer is, yes, very much so. We hope at this point you agree with this
answer. Just think of all the things DNA code for (pretty much everything). Now imagine life
without them. What is left? Is any of it biotic?

DNA is what makes you special, alive and functional. Without DNA you would not
exist. Everything you have, the thing you consider your best feature would not exist without
DNA. DNA directs cell function. If there was no DNA, cell division would not happen—
therefore no differentiation, this means you would not exist neither would your pet. Even
though DNA is not solely responsible for life as we know it is still arguably the most
important factor. Other factors include the environment and experience.
DNA is important for many reasons—so many in fact that we cannot list them all. To name a
few it is important in the fields of genealogy, forensic science, agriculture, and virology.

Conclusion

In conclusion, DNA forms the basis for life. The discovery of the DNA structure has
led to major strides in research, medicine, agriculture and many other fields. Given how
important this structure is to our existence, it only makes sense that its description has
affected so many areas of our lives. We hope at this point you have as much appreciation as
we do for what DNA is and can do, how is differs from RNA, how many lives it has
revolutionized and DNA fingerprinting. At this point, you should also have an appreciation
for what DNA is in biology and what it means for this field.