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Transcript
Outline
25.1
DNA, Chromosomes, and Genes
25.2
Composition of Nucleic Acids
25.3
The Structure of Nucleic Acid Chains
25.4
Base-Pairing in DNA: The Watson-Crick Model
25.5
Nucleic Acids and Heredity
25.6
Replication of DNA
25.7
Structure and Function of RNA
25.8
Transcription: RNA Synthesis
25.9
The Genetic Code
25.10 Translation: Transfer RNA and Protein
Synthesis
Goals
1. What is the composition of the nucleic acids, DNA and
RNA?
Be able to describe and identify the components of
nucleosides, nucleotides, DNA, and RNA.
2. What is the structure of DNA?
Be able to describe the double helix and base pairing in DNA.
3. How is DNA reproduced?
Be able to explain the process of DNA replication.
4. What are the functions of RNA?
Be able to list the types of RNA, their locations in the cell, and
their functions.
5. How do organisms synthesize messenger RNA?
Be able to explain the process of transcription.
6. How does RNA participate in protein synthesis?
Be able to explain the genetic code, and describe the
initiation, elongation, and termination steps of translation.
25.1 DNA, Chromosomes, and Genes
• When a cell is not dividing, its nucleus is
occupied by chromatin, DNA
(deoxyribonucleic acid), twisted around
organizing proteins known as histones.
• During cell division, chromatin organizes
itself into chromosomes.
• Each chromosome contains a different
DNA molecule; the DNA is duplicated so
each new cell receives a complete copy.
25.1 DNA, Chromosomes, and Genes
• Each DNA molecule is composed of genes—
individual segments of the DNA molecule
containing the instructions that direct the
synthesis of a polypeptide.
• Some genes code for functional RNA molecules.
• Organisms differ widely in their numbers of
chromosomes. A horse has 64 chromosomes
(32 pairs), a cat has 38 chromosomes (19 pairs),
a mosquito has 6 chromosomes (3 pairs), and a
corn plant has 20 chromosomes (10 pairs). A
human has 46 chromosomes (23 pairs).
25.2 Composition of Nucleic Acids
• Nucleic acids are polymers known as
polynucleotides.
• Each nucleotide has three parts, a fivemembered cyclic monosaccharide, a
nitrogenous base, and a phosphate group.
25.2 Composition of Nucleic Acids
• Nucleic acids are polymers known as
polynucleotides.
• There are two types of nucleic acids, DNA and
RNA (ribonucleic acid).
• Each nucleotide has three parts: a fivemembered cyclic monosaccharide, a
nitrogenous base, and a phosphate group.
25.2 Composition of Nucleic Acids
The Sugars
• In RNA, the sugar is D-ribose, as indicated
by the name ribonucleic acid.
• In DNA, the sugar is 2-deoxyribose, giving
deoxyribonucleic acid.
25.2 Composition of Nucleic Acids
The Bases
• The five nitrogenous bases found in DNA
and RNA are all derived from two parent
compounds, purine and pyrimidine.
25.2 Composition of Nucleic Acids
The Bases
• In addition to differing in the sugars they
contain, RNA and DNA differ in their
bases:
– Thymine is present only in DNA
molecules (with rare exceptions).
– Uracil is present only in RNA molecules.
– Adenine, guanine, and cytosine are
present in both DNA and RNA.
25.2 Composition of Nucleic Acids
Sugar + Base = Nucleoside
• The sugar and base are connected by a b-Nglycosidic bond to the anomeric carbon of the sugar.
• Nucleoside names are the nitrogenous base name
modified by the suffix -osine for the purine bases
and the suffix -idine for the pyrimidine bases.
• The prefix deoxy- is added for those that contain
deoxyribose.
• To distinguish atoms in the sugar ring from atoms in
the base ring (or rings), numbers without primes are
used for atoms in the base, and numbers with
primes for atoms in the sugar.
25.2 Composition of Nucleic Acids
Nucleoside + Phosphate = Nucleotide
• Nucleotides are the building blocks of nucleic
acids; they are the monomers of DNA and RNA
polymers.
• A nucleotide is a 5’-monophosphate ester of a
nucleoside:
25.2 Composition of Nucleic Acids
Nucleoside + Phosphate = Nucleotide
• Nucleotides are named by adding 5’monophosphate at the end of the nucleoside name.
• Nucleotides containing ribose are ribonucleotides.
• Those that contain 2-deoxy-D-ribose are
deoxyribonucleotides, designated by leading their
abbreviations with a lower case “d”.
• Phosphate groups can be added to any of the
nucleotides to form diphosphate or triphosphate
esters. These esters are named with the nucleoside
name plus diphosphate or triphosphate.
25.2 Composition of Nucleic Acids
25.2 Composition of Nucleic Acids
Summary—Nucleoside, Nucleotide, and Nucleic Acid
Composition
• Nucleoside
– A sugar and a base
• Nucleotide
– A sugar, a base, and a phosphate group
• DNA (deoxyribonucleic acid)
– A polymer of deoxyribonucleotides
– The sugar is 2-deoxy-D-ribose
– The bases are adenine, guanine, cytosine, and thymine
• RNA (ribonucleic acid)
– A polymer of ribonucleotides
– The sugar is D-ribose
– The bases are adenine, guanine, cytosine, and uracil
25.3 The Structure of Nucleic Acid Chains
• The nucleotides in
DNA and RNA are
connected by
phosphate diester
linkages between
the —OH group on
C3’ of the sugar
ring of one
nucleotide and the
phosphate group
on 5’ of the next
nucleotide.
25.3 The Structure of Nucleic Acid Chains
• The structure and function of a nucleic acid
depend on the sequence in which the nucleotides
are connected.
• The sequence of nucleotides in a nucleic acid
chain is read by starting at the 5’ end and
identifying the bases in the order of occurrence.
25.4 Base-Pairing in DNA: The Watson-Crick Model
• Analysis of the nitrogenous bases in DNA
samples from many different species
revealed that the amounts of adenine and
thymine were always equal, and the
amounts of cytosine and guanine were
always equal (A=T and G=C).
• The proportions of each (A/T:G/C) vary
from one species to another.
• This is Chargoff’s Rule, and it suggests
that the bases occur in discrete pairs.
25.4 Base-Pairing in DNA: The Watson-Crick Model
• In 1953, James Watson and Francis Crick proposed
a structure for DNA that accounts for the pairing of
bases and the storage and transfer of genetic
information.
• According to the Watson–Crick model, a DNA
molecule consists of two polynucleotide strands
coiled around each other in a helical, screw-like
fashion.
• The sugar–phosphate backbone is on the outside of
the right-handed double helix, and the heterocyclic
bases are on the inside, so that a base on one
strand points directly toward a base on the second
strand.
25.4 Base-Pairing in DNA: The Watson-Crick Model
25.4 Base-Pairing in DNA: The Watson-Crick Model
• The two strands of the DNA double helix are said to be
antiparallel.
• The stacking of hydrophobic bases in the interior and the
alignment of the hydrophilic groups on the exterior
provide stability to the structure.
• Each pair of bases in the
center of the double helix
is connected by hydrogen
bonding. Adenine and
thymine (A-T) form two
hydrogen bonds, and
cytosine and guanine (C-G)
form three hydrogen bonds.
25.4 Base-Pairing in DNA: The Watson-Crick Model
• The pairing of the bases is complementary.
• Wherever a thymine occurs in one strand, an adenine
falls opposite it in the other strand.
• Wherever a cytosine occurs in one strand, a guanine
falls opposite it on the other strand.
• A and T and C and G occur in equal amounts.
25.5 Nucleic Acids and Heredity
• Duplication, transfer, and expression of genetic
information occur as the result of three
fundamental processes: replication,
transcription, and translation.
– Replication is the process by which a replica, or
identical copy, of DNA is made when a cell divides, so
that each daughter cell has the same DNA.
– Transcription is the process by which DNA is read
and copied. The products of transcription are
ribonucleic acids, which carry the instructions stored
by DNA to the sites of protein synthesis.
– Translation is the process by which the messages
carried by RNA are used to build proteins.
25.6 Replication of DNA
• DNA replication begins in the nucleus with
partial unwinding of the double helix; this
process involves enzymes known as
helicases.
• The unwinding occurs simultaneously in
many specific origins of replication.
• The DNA strands separate, exposing the
bases and forming a “bubble” in which the
replication process can begin.
• At either end are branch points known as
replication forks.
25.6 Replication of DNA
• Multisubunit enzymes called DNA polymerases
facilitate transcription of the single-stranded
DNA.
• Nucleoside triphosphates carrying each of the
four bases are available, and move into place
by forming hydrogen bonds with the bases
exposed on the DNA template strand.
• DNA polymerase catalyzes covalent bond
formation between the 5’ phosphate group of
the arriving nucleoside triphosphate and the 3’
—OH at the end of the growing polynucleotide
strand.
25.6 Replication of DNA
• The template strand can only be read in the 3’ to
5’ direction, and the new DNA strand can grow
only in the 5’ to 3’ direction.
• In each new double helix, one strand is the
template and the other is the newly synthesized
strand. This is semiconservative replication.
25.6 Replication of DNA
• Only the leading strand, is able to grow continuously;
the DNA polymerase traveling in the 3’ to 5’ direction,
is moving in the same direction as the replication fork.
• On the other strand, the DNA polymerase is moving in
the opposite direction as the replication fork.
• The lagging strand is replicated in short segments
called Okazaki fragments. These short DNA segments
are joined together by DNA ligase.
• A human cell contains 3 billion base pairs. Yet a
random error occurs only about once in each 10 billion
to 100 billion bases. The complete copying process in
human cells takes several hours.
25.6 Replication of DNA
25.7 Structure and Function of RNA
• The three types of RNA make it possible
for the information carried by DNA to be
put to use in the synthesis of proteins.
• Ribosomal RNAs Outside the nucleus
are ribosomes—small granular organelles
where protein synthesis takes place. Each
ribosome is a complex consisting of about
60% ribosomal RNA (rRNA) and 40%
protein, with a total molecular mass of
approximately 5,000,000 amu.
25.7 Structure and Function of RNA
• Transfer RNAs (tRNA) are smaller RNAs
that deliver amino acids one by one to
protein chains growing at ribosomes. Each
tRNA carries only one amino acid.
• Messenger RNAs (mRNA) carry
information transcribed from DNA. They
are formed in the nucleus and transported
to ribosomes, where proteins are
synthesized. They are polynucleotides that
carry the same code for proteins as does
the DNA.
25.7 Structure and Function of RNA
•
•
•
•
•
It’s a Ribozyme!
The reaction that removes unneeded sections from newly
synthesized mRNA is accomplished by the mRNA itself acting as
the reaction catalyst.
The slicing out of unneeded bases (introns) and splicing together of
the rest of the mRNA is termed spliceosome activity.
Since then more than 500 ribozymes in different organisms have
been identified.
During protein synthesis in a ribosome, 23S RNA catalyzes the
formation of the peptide bond between amino acids in the growing
protein molecule. The associated proteins, all 31 of them, appear to
provide the necessary structure to maintain the correct threedimensional relationship among the molecules involved in protein
synthesis.
Basic research into the nature and functions of ribozymes continues.
However, applied research is directed toward their use in medical
treatments.
25.8 Transcription: RNA Synthesis
• Ribonucleic acids are synthesized in the
cell nucleus.
• Before leaving the nucleus, all types of
RNA molecules are modified in ways that
enable them to perform different functions.
• In transcription, a small section of the DNA
double helix unwinds, the bases on the
strands are exposed, and complementary
nucleotides are attached.
25.8 Transcription: RNA Synthesis
• rRNA, tRNA, and mRNA are synthesized
in the same manner.
• The DNA strand that is transcribed is the
template strand; its complement in the
original helix is the informational strand.
• The mRNA molecule is an exact RNAduplicate of the DNA informational strand,
with the exception that a U replaces each
T in the DNA strand.
25.8 Transcription: RNA Synthesis
• Transcription begins when RNA polymerase
recognizes a control segment in DNA that
precedes the nucleotides to be transcribed.
• RNA polymerase moves down the DNA
segment, adding complementary
nucleotides to the growing RNA strand.
• Transcription ends when the RNA
polymerase reaches a termination
sequence that signals the end of the
sequence to be copied.
25.8 Transcription: RNA Synthesis
25.8 Transcription: RNA Synthesis
• At the end of transcription, the mRNA
molecule contains a matching base for every
base that was on the informational DNA
strand.
• Only about 10% of the base pairs in DNA
code for genes.
• The code for a gene is contained in one or
more small sections of DNA called an exon.
• The code for a given gene may be interrupted
by a non-coding sequence of bases called an
intron.
25.8 Transcription: RNA Synthesis
• The initial mRNA strand is known as
heterogeneous nuclear RNA (or
hnRNA).
• In the final mRNA molecule released from
the nucleus, the introns have been cut out
and the exons spliced together.
• This is accomplished through the action of
a structure known as a spliceosome, a
protein–RNA complex that removes
introns from nuclear RNA.
25.9 The Genetic Code
• The sequence in an mRNA is a coded
sentence that spells out the order in which
amino acid residues should be joined to form a
protein.
• Codon A sequence of three ribonucleotides
that codes for a specific amino acid or stops
translation.
• Genetic code The sequence of nucleotides,
coded in triplets (codons) in mRNA, that
determines the sequence of amino acids in
protein synthesis.
25.9 The Genetic Code
• Of the 64 possible three-base combinations
in RNA, 61 code for specific amino acids and
3 code for chain termination (the stop
codons).
• The “meaning” of each codon is the genetic
code, and is universal to all but a few living
organisms.
• Most amino acids are specified by more than
one codon.
• Codons are always written in the 5’ to 3’
direction.
25.9 The Genetic Code
25.9 The Genetic Code
DNA informational strand:
5’ ATG CCA GTA GGC CAC TTG TCA 3’
DNA template strand:
3’ TAC GGT CAT CCG GTG AAC AGT 5’
mRNA:
5’ AUG CCA GUA GGC CAC UUG UCA 3’
Protein:
Met
Pro
Val
Gly
His
Leu
Ser
25.9 The Genetic Code
•
•
•
•
•
•
•
•
Viruses and AIDS
Viruses are infectious agents that can replicate only inside living cells.
Virus particles consist of only some nucleic acid and a protein coating.
Once a virus enters a living cell, it takes over the host cell and forces it to
produce virus copies.
The replication of DNA viruses is straightforward: the cell replicates the viral
DNA, the viral DNA is transcribed to RNA and many copies of the capsid
proteins are made.
After an RNA virus infects a cell either the cell must transcribe and produce
proteins directly from the viral RNA template, or else it must first produce DNA
from the viral RNA by reverse transcription. Reverse transcriptase is provided by
the virus itself.
The human immunodeficiency virus (HIV-1) responsible for most cases of AIDS
(Acquired Immune Deficiency Syndrome) is a retrovirus. Development of drugs
for the treatment of AIDS is especially challenging because HIV has the highest
mutation rate of any known virus.
The best success thus far has been with false nucleosides: once incorporated
into the viral DNA, they then slow down production of new viral RNA.
Some AIDS vaccines have shown promise, but no effective vaccine has yet
been developed.
25.10 Translation: Transfer RNA and Protein Synthesis
• Protein synthesis occurs at ribosomes,
which are located outside the nucleus in
the cytoplasm of cells.
• mRNA binds to the ribosome.
• Amino acids are delivered one-by-one by
transfer RNA (tRNA) molecules.
• Amino acids are joined into a specific
protein by the ribosomal “machinery.”
25.10 Translation: Transfer RNA and Protein Synthesis
• Every cell contains more than 20 different tRNAs,
each designed to carry a specific amino acid.
• A tRNA molecule is a single polynucleotide chain
held together by regions of base pairing in a
partially helical structure like a cloverleaf.
• In three dimensions, a tRNA molecule is
L-shaped.
25.10 Translation: Transfer RNA and Protein Synthesis
25.10 Translation: Transfer RNA and Protein Synthesis
• At one end of the L-shaped tRNA molecule, an
amino acid is bonded to its specific tRNA by an
ester linkage between the —COOH of the
amino acid and an —OH group on the last
ribose at the 3’ end of the tRNA chain.
• Individual synthetase enzymes are responsible
for connecting each amino acid with its partner
tRNA in an energy-requiring reaction.
• This reaction is referred to as charging the
tRNA. Once charged, the tRNA is ready to be
used in the synthesis of new protein.
25.10 Translation: Transfer RNA and Protein Synthesis
• At the other end of the tRNA “L” is an
anticodon.
• The anticodon of each tRNA is
complementary to the mRNA codon
designating the amino acid that the tRNA
carries.
• This is how the genetic message of the
codons, is translated into the sequence of
amino acids in a protein.
25.10 Translation: Transfer RNA and Protein Synthesis
25.10 Translation: Transfer RNA and Protein Synthesis
Translation Initiation
• Each ribosome is made up of two subunits called the
small subunit and the large subunit which contain protein
enzymes and ribosomal RNA (rRNA).
• Protein synthesis begins with the binding of an mRNA to
the small subunit of a ribosome, joined by the first tRNA.
The first codon on the 5’ end of mRNA, an AUG, acts as
a “start” signal for the translation machinery and codes
for a methionine-carrying tRNA.
• Initiation is completed when the large ribosomal subunit
joins the small one and the methionine-bearing tRNA
occupies one of the two binding sites on the united
ribosome.
• Met may be removed by post-translational modification.
25.10 Translation: Transfer RNA and Protein Synthesis
Translation Elongation
• A second binding site where the next codon on mRNA is
exposed and the tRNA carrying the next amino acid is
attached.
• A ribozyme in the large subunit catalyzes the new peptide
bond and breaks the bond linking amino acid 1 to its tRNA.
• These energy-requiring steps are fueled by the hydrolysis of
GTP to GDP.
• The first tRNA leaves the ribosome, and the ribosome shifts
three positions (one codon) along the mRNA chain. A second
binding site is opened up to accept the tRNA carrying the next
amino acid.
• A single mRNA can be “read” simultaneously by many
ribosomes. The growing polypeptides increase in length as
the ribosomes move down the mRNA strand.
25.10 Translation: Transfer RNA and Protein Synthesis
Translation Termination
• When synthesis of the protein is completed, a
“stop” codon signals the end of translation.
• An enzyme called a releasing factor then
catalyzes cleavage of the polypeptide chain from
the last tRNA, the tRNA and mRNA molecules are
released from the ribosome, and the two ribosome
subunits separate.
• This step also requires energy from GTP.
• Adding one amino acid to the growing polypeptide
chain requires four molecules of GTP, excluding
the energy needed to charge the tRNA.
25.10 Translation: Transfer RNA and Protein Synthesis
•
•
•
•
•
•
Influenza—Variations on a Theme
Flu is caused by the influenza virus, of which there are three major
types—A, B, and C.
Getting a flu shot can prevent illness from types A and B influenza.
You have to be re-immunized yearly because the influenza virus
mutates.
Flu can cause either an epidemic or a pandemic. Both have
occurred.
Many subtypes of influenza A viruses are also found in animals.
Birds are susceptible to all known subtypes of the influenza A virus
and serve as a reservoir.
Because pigs are susceptible to infection by both avian and human
viruses, they can serve as a “mixing vessel” for the scrambling of
genetic material from human and avian viruses.
In 1918, a strain of influenza that became known as Spanish flu
killed an estimated 20–50 million people worldwide.
Chapter Summary
1.
What is the composition of the nucleic acids, DNA and RNA?
•
Nucleic acids are polymers of nucleotides. Each nucleotide
contains a sugar, a base, and a phosphate group.
•
The sugar is D-ribose in ribonucleic acids (RNAs) and 2-deoxy-Dribose in deoxyribonucleic acids (DNAs). The C5-OH of the sugar
is bonded to the phosphate group, and the anomeric carbon of the
sugar is connected by an N-glycosidic bond to one of five
heterocyclic nitrogen bases.
•
A nucleoside contains a sugar and a base, but not the phosphate
group.
•
In DNA and RNA, the nucleotides are connected by phosphate
diester linkages between the 3’—OH group of one nucleotide and
the 5’ phosphate group of the next nucleotide. DNA and RNA both
contain adenine, guanine, and cytosine; thymine occurs in DNA
and uracil occurs in RNA.
Chapter Summary, Continued
2. What is the structure of DNA?
• The DNA in each chromosome consists of two
polynucleotide strands twisted together in a double
helix.
• The sugar–phosphate backbones are on the outside,
and the bases are in the center of the helix. The bases
on the two strands are complementary—opposite
every thymine is an adenine, opposite every guanine is
a cytosine.
• The base pairs are connected by hydrogen bonds (two
between T and A; three between G and C). Because of
the base pairing, the DNA strands are antiparallel: One
DNA strand runs in the 5’ to 3’ direction and its
complementary partner runs in the 3’ to 5’ direction.
Chapter Summary, Continued
3. How is DNA reproduced?
• Replication requires DNA polymerase enzymes and
deoxyribonucleoside triphosphates.
• The DNA helix partially unwinds and the enzymes
move along the separated DNA strands, synthesizing a
new strand with bases complementary to those on the
unwound DNA strand being copied.
• The enzymes move only in the 3’ to 5’ direction along
the template strand (and thus new DNA strands only
grow in the 5’ to 3’ direction), so that one strand is
copied continuously and the other strand is copied in
segments as the replication fork moves along.
• In each resulting double helix, one strand is the original
template strand and the other is the new copy.
Chapter Summary, Continued
4. What are the functions of RNA?
• Messenger RNA (mRNA) carries the
genetic information out of the nucleus to
the ribosomes in the cytosol, where
protein synthesis occurs.
• Transfer RNAs (tRNAs) circulate in the
cytosol, where they bond to amino acids
that they then deliver to ribosomes for
protein synthesis.
• Ribosomal RNAs (rRNAs) are
incorporated into ribosomes.
Chapter Summary, Continued
5. How do organisms synthesize messenger RNA?
• In transcription, one DNA strand serves as the
template and the other, the informational strand, is not
copied.
• Nucleotides carrying bases complementary to the
template bases between a control segment and a
termination sequence are connected one by one to
form mRNA.
• The primary transcript mRNA (or hnRNA) is identical to
the matching segment of the informational strand, but
with uracil replacing thymine.
• Introns, which are base sequences that do not code for
amino acids in the protein, are cut out before the final
transcript mRNA leaves the nucleus.
Chapter Summary, Continued
6.
•
•
•
•
How does RNA participate in protein synthesis?
The genetic information is read as a sequence of codons—triplets
of bases that give the sequence of amino acids in a protein.
Of the 64 possible codons, 61 specify amino acids and 3 are stop
codons. Each tRNA has at one end an anticodon consisting of
three bases complementary to those of the mRNA codon that
specifies the amino acid it carries.
Initiation of translation is the coming together of the large and
small subunits of the ribosome, an mRNA, and the first amino
acid–bearing tRNA connected at the first of the two binding sites
in the ribosome.
Elongation proceeds as the next tRNA arrives at the second
binding site, its amino acid is bonded to the first one, the first
tRNA leaves, and the ribosome moves along so that once again
there is a vacant second site. These steps repeat until the stop
codon is reached. The termination step consists of separation of
the two ribosome subunits, the mRNA, and the protein.