Molecular Biology

The Structure of DNA and RNA

Dr.Duraid Qassim Alshareef

Consultant in Microbiology and Immunology

Definition:

A nucleic acid is a long molecule made up of smaller molecules called

nucleotides.

Five major discoveries in Nucleic acid understanding as genetic

materials:

1. Nucleic acids were discovered in 1868, when twenty-four-year-old

Swiss physician Friedrich Miescher isolated a new compound from
the nuclei of white blood cells.
This compound was neither a protein nor lipid nor a carbohydrate;
therefore, it was a novel type of biological molecule. Miescher named his
discovery "nuclein," because he had isolated it from the nuclei of cells.
Today, his discovery is known as deoxyribonucleic acid (DNA).

2. Frederick Griffith's Discovery of the Transforming Principle

in Bacterial Organisms:
Frederick Griffith was searching for a vaccine against Spanish flu and was
using two strains of Streptococcus pneumoniae bacteria. During the
process he discovered that gene transfer took place between two different
bacterial strains.
For his experiment, which was conducted in 1928, Griffith used two of the
three strains of Pneumococcus bacteria that had been discovered by the
German bacteriologist Fred Neufeld.
 These bacteria infect and cause pneumonia in mice - The virulent
Type III-S strain - Type III-S has a smooth polysaccharide capsule
covering that protects it from attacks from the host's immune system.
 The non-virulent Type II-R strain - Type II-R does not have a
polysaccharide capsule covering, has a rough appearance and it can be
destroyed by the host's immune system.

Here's what Griffith did and what he observed -

 He injected mice with the Type II-R strain and the mice survived.
 He injected mice with the Type III-S strain and the mice died.
 He heat killed the Type III-S strain and then injected the mice with the
dead bacteria and the mice lived.
 He injected dead Type III-S strain and live Type II-R strain into the
mice and the mice died. He then detected the presence of live Type III-S
strain bacteria with live Type II-R strain bacteria in the blood of the dead
mice.
  This experiment led Griffith to conclude that the dead the Type II-R
bacteria had been transformed by the Type III-S bacteria enabling it
to develop a polysaccharide cover and take on its virulent properties.
 This meant that the bacterial strains did not have fixed and non-
interchangeable properties, which was the thinking at the time. They
were capable of transformation and this clearly indicated gene
transfer. Frederick Griffith was not, however, able to discover how
this transformation took place; he knew about chromosomes and
about nuclein (DNA and RNA) that Frederick Miescher had detected
in 1869, but no one knew for sure if the genetic information was
contained in nucleic acids.

3. Dr. Joachim Hämmerling : (1901 - 1980) was a pioneering Danish-

German biologist funded by Nazi Germany who determined that
the nucleus of a cell controls the development of organisms. 
The groundbreaking experiment came in 1943 when he determined the role
of the nucleus. In his experiments, he removed the nucleus from a specific
species of Acetabulariacalled A. crenulata and grafted it onto the cell of
another a Acetabularia species called A. mediterranea, in which
Hämmerling had removed specific parts of the organism. Shortly thereafter,
the mediterranea regenerated the removed parts, but with the
characteristics from the crenulata species.
This experiment demonstrated that the nucleus contains the genetic
information and controls development. The experiment also proved the
existence of morphogenetic substances, which would eventually become
known as mRNP

4. Alfred Hershey and Martha Chase :

In the mid-twentieth century, scientists were still unsure as to whether DNA
or protein was the genetic material of the cell
 It was known that some viruses consisted solely of DNA and a protein
coat and could transfer their genetic material into hosts

In 1952, Alfred Hershey and Martha Chase conducted a series of

experiments to prove that DNA was the genetic material
 Viruses (T2 bacteriophage) were grown in one of two isotopic
mediums in order to radioactively label a specific viral component
 Viruses grown in radioactive sulfur (35S) had
radiolabelled proteins (sulfur is present in proteins but not DNA)
 Viruses grown in radioactive phosphorus (32P) had
radiolabeled DNA (phosphorus is present in DNA but not proteins)

The viruses were then allowed to infect a bacterium (E. coli) and then the
virus and bacteria were separated via centrifugation
 The larger bacteria formed a solid pellet while the smaller viruses
remained in the supernatant

The bacterial pellet was found to be radioactive when infected by the 32P–

viruses (DNA) but not the 35S–viruses (protein)
 This demonstrated that DNA, not protein, was the genetic material
because DNA was transferred to the bacteria
5. The Watson-Crick Model of DNA (1953):
Deoxyribonucleic Acid (DNA) is a double-stranded, helical molecule. It
consists of two sugar-phosphate backbones on the outside, held together
by hydrogen bonds between pairs of nitrogenous bases on the inside. The
bases are of four types (A, C, G, & T): pairing always occurs between A &
T, and C & G. James Watson (1928 - ) and Francis Crick (1916 - 2004)
realized that these pairing rules meant that either strand contained all the
information necessary to make a new copy of the entire molecule, and that
the order of bases might provide a "genetic code".
 Watson and Crick shared the Nobel Prize in 1962 for their discovery,
along with Maurice Wilkins (1916 - 2004), who had produced a large body
of crystallographic data supporting the mode. Working in the same lab,
Rosalind Franklin (1920 - 1958) had earlier produced the first clear
crystallographic evidence for a helical structure. Crick went on to do
fundamental work in molecular biology and neurobiology. Watson become
Director of the Cold Spring Harbor Laboratory, and headed up the Human
Genome Project in the 1990s.

DNA structure:

DNA is made up of molecules called nucleotides. Each nucleotide contains

a phosphate group, a sugar group and a nitrogen base. 
The four types of nitrogen bases are adenine (A), thymine (T), guanine (G)
and cytosine (C).

The order of these bases is what determines DNA's instructions, or genetic

code. Similar to the way the order of letters in the alphabet can be used to
form a word, the order of nitrogen bases in a DNA sequence forms genes,
which in the language of the cell, tells cells how to make proteins. Another
type of nucleic acid, ribonucleic acid, or RNA, translates genetic information
from DNA into proteins.

The entire human genome contains about3 billion bases and about 20,000
genes.

Nucleotides are attached together to form two long strands that spiral to
create a structure called a double helix. DNA molecules are long — so
long, in fact, that they can't fit into cells without the right packaging. To fit
inside cells, DNA is coiled tightly to form structures we call chromosomes.
Each chromosome contains a single DNA molecule. Humans have 23 pairs
of chromosomes, which are found inside the cell's nucleus.

Chromosome:
 the microscopic threadlike part of the cell that
carries hereditary information in the form of genes. A defining feature of
any chromosome is its compactness.
For instance, the 46 chromosomes found in human cells have a combined
length of 200 nm (1 nm = 10 − 9 metre); if the chromosomes were to be
unraveled, the genetic material they contain would measure roughly 2
metres (about 6.5 feet) in length.
If you took the DNA from all the cells in your body and lined it up, end to
end, it would form a strand 6000 million miles long (but very, very thin)! To
store this important material, DNA molecules are tightly packed around
proteins called histones to make structures called chromosomes.
The largest chromosome, chromosome 1, contains about 8000 genes. The
smallest chromosome, chromosome 21, contains about 300 genes.
Gene:
A gene is a length of DNA that codes for a specific protein. So, for
example, one gene will code for the protein insulin, which is important role
in helping your body to control the amount of sugar in your blood.

Genes are the basic unit of genetics. Human beings have 20,000 to 25,000
genes. These genes account for only about 3 per cent of our DNA. The
function of the remaining 97 per cent is still not clear, although scientists
think it may have something to do with controlling the genes
All humans have the same genes arranged in the same order. And more
than 99.9% of our DNA sequence is the same. But the few differences
between us (all 1.4 million of them!) are enough to make each one of us
unique. On average, a human gene will have 1-3 bases that differ from
person to person. These differences can change the shape and function of
a protein, or they can change how much protein is made, when it's made,
or where it's made.

RNA structure:
Structurally speaking, ribonucleic acid (RNA), is quite similar to DNA.
However, whereas DNA molecules are typically long and double stranded,
RNA molecules are much shorter and are typically single stranded. RNA
molecules perform a variety of roles in the cell but are mainly involved in
the process of protein synthesis (translation) and its regulation.
RNA is typically single stranded and is made of ribonucleotides that are
linked by phosphodiester bonds. A ribonucleotide in the RNA chain
contains ribose (the pentose sugar), one of the four nitrogenous bases (A,
U, G, and C), and a phosphate group. The subtle structural difference
between the sugars gives DNA added stability, making DNA more suitable
for storage of genetic information, whereas the relative instability of RNA
makes it more suitable for its more short-term functions. The RNA-specific
pyrimidine uracil forms a complementary base pair with adenine and is
used instead of the thymine used in DNA. Even though RNA is single
stranded, most types of RNA molecules show extensive intramolecular
base pairing between complementary sequences within the RNA strand,
creating a predictable three-dimensional structure essential for their
function

Functions of RNA in Protein Synthesis

Cells access the information stored in DNA by creating RNA to direct the
synthesis of proteins through the process of translation. Proteins within a
cell have many functions, including building cellular structures and serving
as enzyme catalysts for cellular chemical reactions that give cells their
specific characteristics. The three main types of RNA directly involved in
protein synthesis are messenger RNA (mRNA), ribosomal RNA (rRNA),
and transfer RNA (tRNA).
In 1961, French scientists François Jacob and
Jacques Monod hypothesized the existence of an intermediary between
DNA and its protein products, which they called messenger RNA.

 Evidence supporting their hypothesis was gathered soon afterwards

showing that information from DNA is transmitted to the ribosome for
protein synthesis using mRNA. If DNA serves as the complete library of
cellular information, mRNA serves as a photocopy of specific information
needed at a particular point in time that serves as the instructions to make
a protein.

The mRNA carries the message from the DNA, which controls all of the
cellular activities in a cell. If a cell requires a certain protein to be
synthesized, the gene for this product is “turned on” and the mRNA is
synthesized through the process of transcription ( RNA Transcription). The
mRNA then interacts with ribosomes and other cellular machinery to direct
the synthesis of the protein it encodes during the process
of translation ( Protein Synthesis). mRNA is relatively unstable and short-
lived in the cell, especially in prokaryotic cells, ensuring that proteins are
only made when needed.