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Protein Synthesis
https://youtu.be/h3b9ArupXZg
– DNA specifies the synthesis of proteins in two
stages:
• Transcription, the transfer of genetic information
from DNA into an RNA molecule
• Translation, the transfer of information from RNA
into a protein
Nucleus
DNA
TRANSCRIPTION
RNA
TRANSLATION
Protein
Cytoplasm
Figure 10.8-3
– The function of a gene is to dictate the
production of a polypeptide.
– A protein may consist of two or more different
polypeptides.
From Nucleotides to Amino Acids: An Overview
– Genetic information in DNA is:
• Transcribed into RNA, then
• Translated into polypeptides
– What is the language of nucleic acids?
• In DNA, it is the linear sequence of nucleotide
bases.
• A typical gene consists of thousands of
nucleotides.
• A single DNA molecule may contain thousands of
genes.
– When DNA is transcribed, the result is an
RNA molecule.
– RNA is then translated into a sequence of
amino acids in a polypeptide.
– What are the rules for translating the RNA
message into a polypeptide?
– A codon is a triplet of bases, which codes for
one amino acid.
The Genetic Code
– The genetic code is:
• The set of rules relating nucleotide sequence to
amino acid sequence
• Shared by all organisms
– Of the 64 triplets:
• 61 code for amino acids
• 3 are stop codons, indicating the end of a
polypeptide
Gene 1
DNA molecule
Gene 2
Gene 3
DNA strand
TRANSCRIPTION
RNA
TRANSLATION
Codon
Polypeptide
Amino acid
Figure 10.10
Second base of RNA codon
First base of RNA codon
Leucine
(Leu)
Leucine
(Leu)
Isoleucine
(Ile)
Serine
(Ser)
Stop
Stop
Proline
(Pro)
Threonine
(Thr)
Met or start
Valine
(Val)
Tyrosine
(Tyr)
Alanine
(Ala)
Histidine
(His)
Glutamine
(Gln)
Cysteine
(Cys)
Stop
Tryptophan (Trp)
Arginine
(Arg)
Asparagine
(Asn)
Serine
(Ser)
Lysine
(Lys)
Arginine
(Arg)
Aspartic
acid (Asp)
Glutamic
acid (Glu)
Third base of RNA codon
Phenylalanine
(Phe)
Glycine
(Gly)
Figure 10.11
Transcription: From DNA to RNA
– Transcription:
• Makes RNA from a DNA template
• Uses a process that resembles DNA replication
• Substitutes uracil (U) for thymine (T)
– RNA nucleotides are linked by RNA
polymerase.
Initiation of Transcription
– The “start transcribing” signal is a nucleotide
sequence called a promoter.
– The first phase of transcription is initiation, in
which:
• RNA polymerase attaches to the promoter
• RNA synthesis begins
RNA Elongation
– During the second phase of transcription,
called elongation:
• The RNA grows longer
• The RNA strand peels away from the DNA
template
Termination of Transcription
– During the third phase of transcription, called
termination:
• RNA polymerase reaches a sequence of DNA
bases called a terminator
• Polymerase detaches from the RNA
• The DNA strands rejoin
The Processing of Eukaryotic
RNA
– After transcription:
• Eukaryotic cells process RNA
• Prokaryotic cells do not
– RNA processing includes:
• Adding a cap and tail
• Removing introns
• Splicing exons together to form messenger RNA
(mRNA)
Animation: Transcription
RNA polymerase
DNA of gene
Promoter
DNA
Initiation
Terminator DNA
Elongation
Area shown in
part (a) at left
RNA
RNA nucleotides
RNA polymerase
Termination
Growing RNA
Newly
made
RNA
Completed RNA
Direction of
transcription
Template
strand of DNA
(a) A close-up view of transcription
RNA
polymerase
(b) Transcription of a gene
Figure 10.13
Translation: The Players
– Translation is the conversion from the nucleic
acid language to the protein language.
Messenger RNA (mRNA)
– Translation requires:
•
•
•
•
•
mRNA
ATP
Enzymes
Ribosomes
Transfer RNA (tRNA)
DNA
Cap
RNA
transcript
with cap
and tail
Transcription
Addition of cap and tail
Introns removed Tail
Exons spliced together
mRNA
Coding sequence
Nucleus
Cytoplasm
Figure 10.14
Transfer RNA (tRNA)
– Transfer RNA (tRNA):
• Acts as a molecular interpreter
• Carries amino acids
• Matches amino acids with codons in mRNA using
anticodons
Amino acid attachment site
Hydrogen bond
RNA polynucleotide
chain
Anticodon
tRNA polynucleotide
(ribbon model)
tRNA
(simplified
representation)
Figure 10.15
Ribosomes
– Ribosomes are organelles that:
• Coordinate the functions of mRNA and tRNA
• Are made of two protein subunits
• Contain ribosomal RNA (rRNA)
Next amino acid
to be added to
polypeptide
tRNA binding sites
P site
Growing
polypeptide
A site
mRNA
binding
site
(a) A simplified diagram
of a ribosome
Large
subunit
Small
subunit
Ribosome
tRNA
mRNA
Codons
(b) The “players” of translation
Figure 10.16
Translation: The Process
– Translation is divided into three phases:
• Initiation
• Elongation
• Termination
Initiation
– Initiation brings together:
• mRNA
• The first amino acid, Met, with its attached tRNA
• Two subunits of the ribosome
– The mRNA molecule has a cap and tail that help
it bind to the ribosome.
Blast Animation: Translation
Cap
Start of genetic
message
End
Tail
Figure 10.17
– Initiation occurs in two steps:
• First, an mRNA molecule binds to a small
ribosomal subunit, then an initiator tRNA binds to
the start codon.
• Second, a large ribosomal subunit binds, creating
a functional ribosome.
Met
Large
ribosomal
subunit
Initiator
tRNA
P site
A site
mRNA
Start
codon
Small ribosomal
subunit
Figure 10.18
Elongation
– Elongation occurs in three steps.
• Step 1, codon recognition:
–
the anticodon of an incoming tRNA pairs with the mRNA codon
at the A site of the ribosome.
• Step 2, peptide bond formation:
–
–
The polypeptide leaves the tRNA in the P site and attaches to
the amino acid on the tRNA in the A site
The ribosome catalyzes the bond formation between the two
amino acids
• Step 3, translocation:
–
–
The P site tRNA leaves the ribosome
The tRNA carrying the polypeptide moves from the A to
the P site
Animation: Translation
Amino acid
Polypeptide
P site
mRNA
Anticodon
A
site
Codons
Codon recognition
ELONGATION
Stop
codon
New
peptide
bond
Peptide bond formation
mRNA
movement
Translocation
Figure 10.19-4
Termination
– Elongation continues until:
• The ribosome reaches a stop codon
• The completed polypeptide is freed
• The ribosome splits into its subunits
Review: DNA RNA Protein
– In a cell, genetic information flows from DNA
to RNA in the nucleus and RNA to protein in
the cytoplasm.
Transcription
RNA polymerase
Polypeptide
Nucleus
DNA
mRNA
Stop
codon
Intron
RNA processing
Cap
Tail
Termination
mRNA
Intron
Anticodon
Ribosomal Codon
subunits
Amino acid
tRNA
ATP
Enzyme
Amino acid
attachment
Initiation
of translation
Elongation
Figure 10.20-6
– As it is made, a polypeptide:
• Coils and folds
• Assumes a three-dimensional shape, its tertiary
structure
– Several polypeptides may come together,
forming a protein with quaternary structure.
– Transcription and translation are how genes
control:
• The structures
• The activities of cells
Mutations
– A mutation is any change in the nucleotide
sequence of DNA.
– Mutations can change the amino acids in a
protein.
– Mutations can involve:
• Large regions of a chromosome
• Just a single nucleotide pair, as occurs in sickle cell
anemia
Types of Mutations
– Mutations within a gene can occur as a result
of:
• Base substitution, the replacement of one base by
another
• Nucleotide deletion, the loss of a nucleotide
• Nucleotide insertion, the addition of a nucleotide
Normal hemoglobin DNA
Mutant hemoglobin DNA
mRNA
mRNA
Normal hemoglobin
Sickle-cell hemoglobin
Figure 10.21
– Insertions and deletions can:
• Change the reading frame of the genetic message
• Lead to disastrous effects
Mutagens
– Mutations may result from:
• Errors in DNA replication
• Physical or chemical agents called mutagens
– Although mutations are often harmful, they
are the source of genetic diversity, which is
necessary for evolution by natural selection.
mRNA and protein from a normal gene
(a) Base substitution
Deleted
(b) Nucleotide deletion
Inserted
(c) Nucleotide insertion
Figure 10.22
VIRUSES AND OTHER NONCELLULAR INFECTIOUS
AGENTS
– Viruses exhibit some, but not all,
characteristics of living organisms. Viruses:
• Possess genetic material in the form of nucleic
acids
• Are not cellular and cannot reproduce on their
own.
Bacteriophages
– Bacteriophages, or phages, are viruses that
attack bacteria.
Animation: Phage T2 Reproductive Cycle
Protein coat
DNA
Figure 10.24
Head
Bacteriophage
(200 nm tall)
Tail
Tail
fiber
DNA
of
virus
Bacterial cell
Colorized TEM
Figure 10.25
Plant Viruses
– Viruses that infect plants can:
• Stunt growth
• Diminish plant yields
• Spread throughout the entire plant
Animation: Phage Lambda Lysogenic and Lytic Cycles
Animation: Phage T4 Lytic Cycle
Phage
Phage attaches
to cell.
Phage DNA
Bacterial
chromosome (DNA)
Phage injects DNA
Many cell divisions
Occasionally a prophage
may leave the bacterial
chromosome.
LYSOGENIC
CYCLE
Phage DNA
circularizes.
Prophage
Lysogenic bacterium
reproduces normally,
replicating the prophage
at each cell division.
Phage DNA is inserted into the
bacterial chromosome.
Figure 10.26b
Phage lambda
E. coli
Figure 10.26c
– Viral plant diseases:
• Have no cure
• Are best prevented by producing plants that resist
viral infection
RNA
Protein
Tobacco mosaic virus
Figure 10.27
Animal Viruses
– Viruses that infect animals are:
• Common causes of disease
• May have RNA or DNA genomes
– Some animal viruses steal a bit of host cell
membrane as a protective envelope.
Membranous
envelope
Protein spike
RNA
Protein coat
Figure 10.28
– The reproductive cycle of an enveloped RNA
virus can be broken into seven steps.
Animation: Simplified Viral Reproductive Cycle
Viral RNA (genome)
Virus
Plasma membrane
of host cell
Entry
Viral RNA
(genome)
mRNA
Protein spike
Protein coat
Envelope
Uncoating
RNA synthesis
by viral enzyme
RNA synthesis
(other strand)
Protein
synthesis
Assembly
New viral proteins
Template
New viral
genome
Exit
Figure 10.29
Mumps virus
Protein spike
Colorized TEM
Envelope
Figure 10.29c
The Process of Science:
Do Flu Vaccines Protect the
Elderly?
– Observation: Vaccination rates among the
elderly rose from 15% in 1980 to 65% in 1996.
– Question: Do flu vaccines decrease the
mortality rate among those elderly people who
receive them?
– Hypothesis: Elderly people who were
immunized would have fewer hospital stays and
deaths during the winter after vaccination.
© 2010 Pearson Education, Inc.
– Experiment: Tens of thousands of people
over the age of 65 were followed during the
ten flu seasons of the 1990s.
– Results: People who were vaccinated had a:
• 27% less chance of being hospitalized during the
next flu season and
• 48% less chance of dying
Blast Animation: HIV Structure
Percent reduction in severe illness
and death in vaccinated group
50
48
40
30
27
20
16
10
0
0
Winter months
(flu season)
Hospitalizations
Summer months
(non-flu season)
Deaths
Figure 10.30a
HIV, the AIDS Virus
– HIV is a retrovirus, an RNA virus that
reproduces by means of a DNA molecule.
– Retroviruses use the enzyme reverse
transcriptase to synthesize DNA on an RNA
template.
– HIV steals a bit of host cell membrane as a
protective envelope.
Envelope
Surface protein
Protein
coat
RNA
(two identical
strands)
Reverse
transcriptase
Figure 10.31
– The behavior of HIV nucleic acid in an
infected cell can be broken into six steps.
Blast Animation: AIDS Treatment Strategies
Animation: HIV Reproductive Cycle
Viral RNA
Reverse
Cytoplasm
transcriptase
Nucleus
Double
stranded
DNA
Viral
RNA
and
proteins
Chromosomal
DNA
Provirus
RNA
SEM
DNA
strand
HIV (red dots) infecting
a white blood cell
Figure 10.32
– AIDS (acquired immune deficiency syndrome)
is:
• Caused by HIV infection and
• Treated with drugs that interfere with the
reproduction of the virus
Thymine
(T)
Part of a T nucleotide
AZT
Figure 10.33
Viroids and Prions
– Two classes of pathogens are smaller than
viruses:
• Viroids are small circular RNA molecules that do
not encode proteins
• Prions are misfolded proteins that somehow
convert normal proteins to the misfolded prion
version
– Prions are responsible for neurodegenerative
diseases including:
•
•
•
•
Mad cow disease
Scrapie in sheep and goats
Chronic wasting disease in deer and elk
Creutzfeldt-Jakob disease in humans
EVOLUTION
• If it weren’t for evolution, we would all be
prokaryotic unicellular beings!
• So how did we evolve from that into a
human being?
Here it comes…
• Viruses and Mutations!
• These two vectors are the key to
evolution. Mutations are generally
considered to be in two categories:
• Nucleotide substitution and
• Nucleotide insertions or deletions
– Although mutations are often harmful, they
are the source of genetic diversity, which is
necessary for evolution by natural selection.
mRNA and protein from a normal gene
(a) Base substitution
Deleted
(b) Nucleotide deletion
Inserted
(c) Nucleotide insertion
Figure 10.22
Mutagens
• (what causes mutations) normally they are
spontaneous (no known cause, accidental)
Errors during DNA replication or
recombination
• Chemical agents can be mutagens
• High energy radiation (sun, A-bombs etc.)
• X-rays
• carcinogens
Evolution Connection:
Emerging Viruses
– Emerging viruses are viruses that have:
• Appeared suddenly or
• Have only recently come to the attention of science
© 2010 Pearson Education, Inc.
Figure 10.35
Figure 10.UN7
VIRUSES AND OTHER
NONCELLULAR INFECTIOUS
AGENTS
– Viruses exhibit some, but not all,
characteristics of living organisms. Viruses:
• Possess genetic material in the form of nucleic
acids
• Are not cellular and cannot reproduce on their
own.
Bacteriophages
– Bacteriophages, or phages, are viruses that
attack bacteria.
Protein coat
DNA
Figure 10.24
– Phages have two reproductive cycles.
(1) In the lytic cycle:
–
–
Many copies of the phage are made within the bacterial
cell, and then
The bacterium lyses (breaks open)
(2) In the lysogenic cycle:
–
–
The phage DNA inserts into the bacterial chromosome
and
The bacterium reproduces normally, copying the phage at
each cell division
Head
Bacteriophage
(200 nm tall)
Tail
Tail
fiber
DNA
of
virus
Bacterial cell
Colorized TEM
Figure 10.25
Phage lambda
E. coli
Figure 10.26c
– Viral plant diseases:
• Have no cure
• Are best prevented by producing plants that resist
viral infection
Plant viruses may use RNA instead of DNA
RNA
Protein
Tobacco mosaic virus
Figure 10.27
Animal Viruses
– Viruses that infect animals are:
• Common causes of disease
• May have RNA or DNA genomes
– Some animal viruses steal a bit of host cell
membrane as a protective envelope.
Membranous
envelope
Protein spike
RNA
Protein coat
Figure 10.28
– New viruses can arise by:
• Mutation of existing viruses
• Spread to new host species