ENGINEERING
BIOLOGY:
NUCLEIC ACIDS
Richa Sharma
Class III
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DNA or RNA?
DEOXYRIBO NUCLEIC ACID RIBO NUCLEIC ACID
• In today’s cells, deoxyribonucleic acid (DNA) stores genetic information and is
replicated. Relatively few researchers favour the hypothesis that life began as a
DNA or protein molecule.
• Instead, the RNA world hypothesis proposes that there was a stage in the
evolution of life when ribonucleic acid (RNA) both stored the genetic information
and catalyzed its own replication. There is compelling evidence that RNA world
existed on early Earth.
• Once the first self-replicating molecules evolved, chance errors in the copying
process created variations that would undergo natural selection—the
evolutionary process by which individuals, in this case molecules, with certain
attributes reproduce more frequently than others. At this point, chemical evolution
was over and biological evolution started.
• Prebiotic soup experiment: The minerals used there preferentially bound to ribose
(a part of RNA), effectively enriching and concentrating ribose on their surface.
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Nucleic acid monomers
• Nucleic acids are polymers made up of monomers called nucleotides
• The sugar is the central component of the nucleotide, much like the α-carbon in
amino acids. The five carbons in this sugar are labelled with numbers and prime
symbols (‘) to provide a frame of reference. For example, the base is attached to
the 1’ carbon and the phosphate group is attached to the 5’ carbon.
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Nucleotides
• Ribose and deoxyribose: both of these sugars have an -OH group bonded to the 3’
carbon, but ribose has an -OH group bonded to the 2’ carbon while deoxyribose
has an H at the same location—a difference of just a single oxygen atom.
• The N- bases, belong to structural groups called purines and pyrimidines.
• The purines are adenine (A) and guanine (G); the pyrimidines are cytosine (C),
uracil (U), and thymine (T).
• The two rings in adenine and guanine are formed from nine atoms, compared to
the six atoms that make a single ring in each pyrimidine. This makes remembering
which bases are purines easy, since both adenine and guanine include “nine” in
their names
• Ribonucleotides use uracil (U), deoxyribonucleotides use thymine (T)
• Phosphate + Ribose sugar + N-base (A, U, G, C) = Ribonucleotide
• Phosphate + Deoxyribose sugar + N-base (A, T, G, C) = Deoxyribonucleotide
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Nucleotide polymerization
• Condensation reactions between the hydroxyl
on the sugar component of one nucleotide and
the phosphate group of another nucleotide. The
reaction forms a new covalent bond—called a
phosphodiester linkage, or a phosphodiester
bond
• Directional: In a strand of RNA or DNA, one end
has an unlinked 5’ phosphate while the other end
has an unlinked 3’ hydroxyl meaning the groups
are not bonded to another nucleotide.
• By convention, the sequence of bases found in an
RNA or DNA strand is always written in the 5’ →
3’ direction, with the nucleotides denoted as
letters of the base they contain. For example, a
DNA sequence consisting of six nucleotides might
be ATTAGC.
• It would take roughly 6 billion such letters to write
the primary structure of DNA in most cells. 5
Polymerization thermodynamics
• Not spontaneous. An input of energy is needed.
• Polymerization can take place in cells because the potential
energy of the nucleotide monomers is first raised by
reactions that add two phosphate groups to the
ribonucleotides or deoxyribonucleotides, creating
nucleoside triphosphates or “activated nucleotides.”
• Phosphates are negatively charged and like charges repel.
Linking two or more phosphates together generates a
covalent bond that carries a large amount of potential energy
due to the strong repulsive forces. And system will try to
minimize potential energy
• Experiment showed that
if activated nucleotides
were mixed with minerals
they could synthesize
50 nucleotide long RNA molecules Adenosine triphosphate 6
Two strands
DNA structure arranged
side-by-side
• PRIMARY STRUCTURE
with bases
facing inside
• DNA molecules have a
sugar–phosphate backbone,
created by phosphodiester
linkages, and a sequence of any of
four nitrogenous bases that extend
from it.
• SECONDARY STRUCTURE
• Erwin Chargaff had established
two empirical rules: (1) The
number of purines in a given DNA
molecule is equal to the number of
pyrimidines, and (2) the DNA
molecule has an equal number of
T’s and A’s, and it has an equal
number of C’s and G’s.
H bond occurs only between The bases are
• No.of purines = No.of pyrimidines
specific purine and pyrimidine perpendicular in
• No.of A = No.of T, pair. A makes 2 bonds with T. axis to the
No.of G = No.of C
G makes 3 bonds with C. backbone, like
• Structural data of DNA Only if they are 180 deg flipped rungs in a ladder
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Bonds stabilizing the structure
• The two parallel strands of DNA must be oriented
in opposite directions— one strand runs in the 5’
→ 3’ direction while the other runs 3’ → 5’.
Strands with this orientation are said to be
antiparallel.
• DNA is put together like a ladder. The antiparallel
sugar–phosphate backbones form the supports of
the ladder, and the base pairs form its rungs.
• The carbon-nitrogen ring structure is mostly
nonpolar. Thus hydrophobic interactions cause
double-stranded DNA to twist into a helix to
minimize contact between the hydrophobic rings
and surrounding water molecules.
• The paired strands are further stabilized by van
der Waals interactions between the tightly
packed bases.
• The negatively charged phosphate groups facing
the exterior of the molecule make the double
helix hydrophilic overall and thus soluble in
aqueous solutions. Tertiary structure 8
DNA contains information
• The four nitrogenous bases function like letters of the alphabet. A sequence of
bases is like the sequence of letters in a word—it has meaning. DNA stores the
information required for the organism’s growth and reproduction
• Does the information contained within DNA allow it to be replicated?
• One strand has bases specific against the 2nd strand: Complementary base
pairing. This means that if one strand is present we can easily predict what the
other strand will be.
• DNA’s primary structure serves as a template for the synthesis of a
complementary strand, meaning that DNA contains the information required
for a copy of itself to be made.
• But DNA can’t catalyze the reactions needed to self-replicate. Its double helix is
very stable structure. Unlike protein enzymes they are not flexible to bind to a
substrate/reactant. DNA structure is unreactive and there is virtually no support
for the hypothesis that the first life-form consisted of DNA alone
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DNA replication
• Strand separation requires energy
input (heating at 95 deg C)
• New deoxyribo nucleotides need to
be added that form the new
strands
• Identical copies of double-stranded
DNA is created
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RNA structure
PRIMARY STRUCTURE
• RNA has a primary structure consisting of four
types of nitrogenous bases extending from a
sugar–phosphate backbone.
1. The sugar in the sugar–phosphate backbone of
RNA is ribose, not deoxyribose as in DNA.
2. The pyrimidine base thymine does not exist in
RNA. Instead, RNA contains the closely related SECONDARY STRUCTURE
pyrimidine base uracil. Complementary base pairing
• The hydroxyl (-OH) group on the 2’ carbon of A two hydrogen bonds with U,
ribose is very reactive. When RNA molecules G three hydrogen bonds with C.
fold in certain ways, the hydroxyl group can Bases on one part of an RNA
attack the phosphate linkage between strand fold over and align with
nucleotides, which would generate a break in bases on another part of the same
the sugar–phosphate backbone. This -OH group strand, the two sugar–phosphate
makes RNA much less stable than DNA, but as strands are antiparallel. This also
you will see later, it can also support other results in a helical structure but in
catalytic activities.
a single nucleic acid molecule.11
• Several other types of RNA secondary structures except hairpin are possible, each
involving a different length and arrangement of base-paired segments. Like the
α-helices and β-pleated sheets observed in many proteins, RNA secondary structures
will form spontaneously. The bases are brought together by hydrophobic
interactions and stabilized by hydrogen bonding and van der Waals interactions.
TERTIARY STRUCTURE
• RNA molecules can also have tertiary structure, which arises when secondary
structures fold into more complex shapes. RNA molecules are much more diverse in
size, shape, and reactivity than DNA molecules.
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RNA functions
• RNA is a nucleic acid like DNA, but RNA folds into
complex three dimensional shapes much like proteins.
These molecules help process information stored in
DNA and synthesize proteins, among other things.
• RNAs with such catalytic activity are called ribozymes,
or RNA enzymes, because they catalyze reactions
similar to protein enzymes.
• The three-dimensional nature of ribozymes is vital to
their catalytic activity. To catalyze a chemical reaction,
substrates must be brought together in an environment
that will promote the reaction. As with protein
enzymes, the region of the ribozyme that is responsible
for this activity is called the active site.
• Fewribozymes catalyze both the hydrolysis and the
condensation of phosphodiester linkages in RNA.
• Their
existence raised the possibility that an RNA
molecule could polymerize a copy of itself. Such a
molecule could qualify as the first living entity.
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Experiments to prove RNA world
• Different groups of researchers made several experiments where they could select
ribozymes from several RNA molecules, that could catalyse formation of
ribonucleotides and other RNAs.
• This proved clarity how RNAs could have ruled in the “RNA world”
• Most of the ribozymes in modern cells play key roles in the synthesis of proteins. If
these ribozymes were removed from cells, then proteins could no longer be made.
• The RNA world preceded proteins. Then proteins took over and catalysed important
reactions.
• 3 requisites of life fulfilled:
1. Information Proteins and ribozymes were processing information stored in nucleic
acids for the synthesis of more proteins.
2. Replication Enzymes, and possibly ribozymes, were replicating the nucleic acids
that stored the hereditary information.
3. Evolution Random changes in the nucleic acids led to the synthesis of different
proteins and ribozymes. Selective advantages resulting from some of these changes
allowed for the evolution of new functions.
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• In early Earth nucleic acids and proteins would have been
constantly fed with thermal and chemical energy.
• To gain independence from requirement of external energy, there
was a necessity to store this energy as something more portable
• This energy storage could be used anywhere and anytime and is
called carbohydrates
Next?
Carbohydrates
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