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Nucleic

Nucleic Acids
Acids and
and Heredity
Heredity
Chapter
Chapter 55

DR. LEONARDO C. MEDINA, JR.

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Chapter Outline
1 Molecules of Heredity – A 7 DNA Replication
Link 8 RNA: Genetic
2 Bases and Nucleosides Transcription
3 Nucleotides: Phosphate 9 The Genetic Code
Esters 10 Genes and Medicine
4 High-Energy Nucleotides 11 Biosynthesis of Proteins
5 Polynucleotides; Nucleic 12 Changing the Genome:
Acids Mutations and Genetic
6 Structure of DNA Engineering

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Molecules of Heredity –
A Link

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• Suspended in the nuclei of cells are
chromosomes, which consist largely
of proteins and nucleic acids.

• A simple protein bonded to a nucleic


acid is called a nucleoprotein.

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•There are two types of nucleic
acids:
1.Deoxyribonucleic acid (DNA) –
contain the sugar deoxyribose
2.Ribonucleic acid (RNA) –
contain the sugar ribose
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Bases and
Nucleosides

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• Nucleic acids are complex chemicals that
combine several different classes of
smaller molecules.
• We begin our examination of nucleic acids
by learning about a critical part of these
molecules, two classes of heterocyclic
bases called the purines and pyrimidines.
N
N N

N
H N N
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purine, C5H4N4 pyrimidine, C4H4N2
Purine and pyrimidine bases found in living matter.
These bases must be available to the cell in order to
reproduce genetic information (DNA).

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Nucleosides
• A nucleoside is formed when either a
purine or pyrimidine base is linked to a
sugar molecule, usually D-ribose or
D-2’-deoxyribose.

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Structures of typical ribonucleosides and 10
deoxyribonucleosides.
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Nucleotides:
Phosphate Esters

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Nucleotides
• A more complex set of biological molecules is
formed by linking phosphate groups to
nucleosides.
• Phosphate esters of nucleosides are termed
nucleotides.

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Examples of nucleotides

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Structures of ADP and ATP.

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High-Energy
High-Energy
Nucleotides

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High-Energy Nucleotides
• Nucleotides have a central role in the
energy transfers in many metabolic
processes.
• ATP and ADP are especially important
in these processes, since these two
nucleotides store and release energy to
the cells and tissues.

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ADP and ATP
• Energy is released during the hydrolysis of high-
energy phosphate anhydride bonds in ADP and
ATP.
• In the hydrolysis, ATP forms ADP and inorganic
phosphate (Pi) yielding about 35 kJ of energy per
mole of ATP:
energy storage
ATP + H2O 
 ADP + Pi + ~35 kJ
energy utilization

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Polynucleotides;
Nucleic Acids

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RNA
• Ribonucleic acid (RNA) is a
polynucleotide that, upon hydrolysis,
yields a ribose, phosphoric acid, and
the four purine and pyrimidine bases
adenine, guanine, cytosine, and uracil.

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DNA
• Deoxyribonucleic acid (DNA) is a
polynucleotide that, upon hydrolysis, yields
a D-2’-deoxyribose, phosphoric acid, and
the four purine and pyrimidine bases
adenine, guanine, cytosine, and thymine.

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A segment of RNA consisting of the four
nucleotides adenosine monophosphate,
cytidine monophosphate, guanosine
monophosphate, and uridine
monophosphate

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Structure of DNA

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DNA

• Deoxyribonucleic acid (DNA) is a


polymeric substance made up of four
nucleotides dAMP, dGMP, dCMP, and
dTMP.

• The size of the DNA polymer varies with


the complexity of the organism; more
complex organisms tend to have larger
DNAs.
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Right: Double-
stranded helical
structure of DNA
(… denotes a
hydrogen bond
between adjoining
bases).
Left: Spacefilling
model of DNA. The
sugar-phosphate
backbone is colored
yellow; the bases are
blue. 26
DNA segment
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Hydrogen bonding between
the complementary bases
thymine and adenine (T…A)
and cytosine and guanine
(C…G).

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Condensed form
of DNA. After
the DNA
polymer wraps
twice around the
histone protein
aggregates
(shown as round
balls), it coils
around a central
axis to form a
solenoid
structure.
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DNA Replication

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DNA Replication
• The polymeric DNA molecule is the
chemical basis for heredity.
• The genetic information needed for
transmitting a species’ characteristics is
coded along the polymeric chain.
• Although the chain is made from only four
different nucleotides, the information
content of DNA resides in the sequence of
these nucleotides.

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Genome
• The genome is the sum of all hereditary
material contained in a cell.

• Within eucaryotic genome are


chromosomes, which are long threadlike
bodies composed of nucleic acids and
proteins that contain the fundamental units
of heredity, called genes.

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• A gene is a segment of the DNA chain that
controls the formation of a molecule of
RNA.
• In turn, many RNAs determine the amino
acid sequence for specific polypeptides or
proteins.
• Usually one gene directs the synthesis of
only one polypeptide or protein molecule.
• The cell has the capability of producing a
multitude of different proteins, because
each DNA molecule contains a large
number of different genes. 33
Replication
• For life to continue relatively
unchanged, genetic information must
be reproduced exactly each time a cell
divides.

• Replication is the biological process


for duplicating the DNA molecule.

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Semiconservative replication of DNA 35
Semiconservative Replication of DNA
• The two helices unwind, separating at the
hydrogen bonds.
• Each strand then serves as a template,
recombining with the proper nucleotides
and forming two new double-stranded
helices.
• The newly synthesized DNA strands are
the ones shown in red (Figure 31.10).
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Semiconservative replication of DNA 37
The basic
replication
process.

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The Basic Replication Process

• Arrows indicate the direction of DNA synthesis.


• Between (1) and (2), the template DNA strands
unwind, and some synthesis occurs for both
daughter strands.
• Moving to (3), the DNA fragments are connected
on one daughter strand, while DNA synthesis
continues on the other strand and the template
strands unwind further.
• DNA synthesis again takes place for both daughter
strands (4). 39
The basic
replication
process.

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DNA Cell Division and Cloning
• The DNA content of cells doubles just
before the cell divides, and one-half of
the DNA goes to each daughter cell.
• After cell division is completed, each
daughter cell contains DNA and the
full genetic code that was present in
the original cell.
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DNA, Cancer, and Chemotherapy
• Scientists understood a key principle about
tissue growth once they realized that cells
must replicate DNA in order to reproduce.
• For example, fast growing cancer cells must
make DNA much faster than normal cells.
• Thus, many common cancer therapeutic
agents are designed to interfere with DNA
replication.

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RNA: Genetic
Transcription

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RNA vs. DNA
• One of the main functions of DNA is to direct
the synthesis of ribonucleic acids (RNAs).
• RNA differs from DNA in the following ways:
(1) It consists of a single polymeric strand of
nucleotides rather than a double helix.
(2) It contains the pentose D-ribose instead of D-2’-
deoxyribose.
(3) It contains the pyrimidine base uracil instead of
thymine.
(4) Some types of RNA have a significant number of
modified bases in addition to the common four.
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RNA vs. DNA
• RNA also differs functionally from DNA:
– Whereas DNA serves as the storehouse of
genetic information, RNA is used to process
this information into proteins.
– Three types of RNA are needed to produce
proteins:
1. ribosomal RNA (rRNA)
2. messenger RNA (mRNA)
3. transfer RNA (tRNA)
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Ribosomal RNA (rRNA)
• More than 80% of the cellular RNA is
ribosomal RNA.
• It is found in the ribosomes, where it is
associated with protein proportions of
about 60-65% protein to 30-35%
rRNA.
– Ribosomes are sites for protein synthesis.

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Messenger RNA (mRNA)
• Messenger RNA carries genetic
information from DNA to the
ribosomes.
• It is a template made from DNA, and it
carries the code that directs the
synthesis of proteins.

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Transfer RNA (tRNA)
• The primary function of tRNA is to
bring amino acids to the ribosomes for
incorporation into protein molecules.
• Consequently, at least one tRNA exists
for each of the 20 amino acids required
for proteins.

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Representations of tRNA. The anticodon triplet
(UUC) located at the lower loop is
complementary to GGA (which is the code49 for
glycine) on mRNA.
Transcription
• The making of RNA from DNA is
called transcription.
• When the nucleotide sequence of one
strand of DNA is transcribed into a
single strand of RNA, genetic
information is copied from DNA to
RNA.
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Transcription of
RNA from
DNA. The sugar
in RNA is
ribose. The
complementary
base of adenine
is uracil. After
transcription is
complete, the
new RNA
separates from
its DNA
template and
travels to
another location
for further use.
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A flow diagram representing the processing of
cellular genetic information. 52
RNA, Cancer, and Chemotherapy
• Cancer results from a loss of cell control.
• The importance of transcription control is
emphasized by the discovery of
oncogenes.
– These genes are present in cancerous or
malignant cells and code for proteins that
control cell growth.
– Cancerous cells lose control of oncogene
transcription.
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RNA, Cancer, and Chemotherapy
• There are genes that actively block cancer
development – the tumor-suppressor
genes.
• These genes code for proteins that allow
cell growth only if the cells are correctly
functioning.
• Potential cancer cells are automatically
eliminated (apoptosis).
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The Genetic Code

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Codons
• How does the information stored in DNA
specify the synthesis of so many different
proteins??
• There must be a code that lies with the four
bases: adenine, guanine, cytosine, and
thymine.

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Codons
• We now know that each code word
requires a sequence of three nucleotides.
• The code is therefore a triplet.
• Each triplet of three nucleotides is called a
codon.
• In general, each codon specifies one
amino acid.
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This table shows the sequence of nucleotides in the triplet codons of
mRNA that specify a given amino acid. For example, UUU or UUC
is the codon for Phe, UCU is the codon for Ser, and CAU of CAC 58
is
the codon for His.
Genes and
Medicine

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Two facts have been known for many years:
(1) Most human traits can be traced to the
genetic makeup of the individual
(2) Some diseases (e.g. sickle-cell anemia and
Tay-Sach’s disease) occur mainly within
certain ethnic groups, clearly indicating a
genetic connection for these maladies.

These two facts motivated scientists to


learn more about the human genome.
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Biosynthesis of
Proteins
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Biosynthesis of Proteins
1. mRNA leaves the cellular nucleus and
travels to the cytoplasm.
2. Initiation
3. Elongation
4. Termination

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Biosynthesis of Proteins. Step 1, initiation: mRNA enters
and complexes with the ribosomes. tRNA carrying an amino
acid (aminoacyl-tRNA) enters the ribosome and attaches to
mRNA at its complementary codon.

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Step 2: elongation: Another aminoacyl-tRNA enters the
ribosome and attaches to the next codon on mRNA. The
peptide chain elongates when a peptide bond is formed
by the transfer of the peptide chain from the initial (Met)
to the incoming amino acid. This sequence is repeated
until the protein chain of amino acids is complete.

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• Step 3: termination
• The sequence ends when a
termination codon moves onto the
ribosome.

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Biosynthesis of Proteins

• All of these amazing, coordinated steps


are accomplished at a high rate speed –
about 1 minute for a 146-amino-acid
chain of human hemoglobin.

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Changing the Genome:
Mutations and
Genetic Engineering

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Mutations
• From time to time, a new trait appears in
an individual that is not present in either
its parents or its ancestors.
• These traits, which are generally the
result of genetic or chromosomal
changes, are called mutations.
• Some mutations are beneficial, but most
are harmful.
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Mutagen
• Mutations occur spontaneously or are
caused by chemical agents or various
types of radiation, such as X-rays,
cosmic rays, and ultraviolet rays.
• The agent that causes the mutation is
called a mutagen.

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