DNA

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DNA
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Saboteurs Inside Our Cells

• The invasion and damage of cells by the
  herpesvirus can be compared to the actions of a
  saboteur intent on taking over a factory
• The herpesvirus hijacks the host cells molecules
  and organelles to produce new copies of the virus

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• Viruses provided some of the earliest evidence
  that genes are made of DNA

• Molecular biology studies how DNA serves as the
  molecular basis of heredity

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10.1 Experiments showed that DNA is the genetic
material
THE STRUCTURE OF THE GENETIC MATERIAL

• The Hershey-Chase experiment showed that certain
  viruses reprogram host cells to produce more
  viruses by injecting their DNA

Head
DNA
Tail
Tailfiber
Figure 10.1A
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• The Hershey-Chase Experiment

Agitate in a blender to separate phages outside
the bacteria from the cells and their contents.
Centrifuge the mixture so bacteria form a pellet
at the bottom of the test tube.
Measure the radioactivity in the pellet and
liquid.
Mix radioactivelylabeled phages with bacteria.
The phages infect the bacterial cells.
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2
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Radioactiveprotein
Emptyprotein shell
Radioactivityin liquid
Phage
Bacterium
PhageDNA
DNA
Batch 1Radioactiveprotein
Centrifuge
Pellet
RadioactiveDNA
Batch 2RadioactiveDNA
Centrifuge
Radioactivityin pellet
Pellet
Figure 10.1B
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• Phage reproductive cycle

Phage attaches to bacterial cell.
Phage injects DNA.
Phage DNA directs host cell to make more phage
DNA and protein parts. New phages assemble.
Cell lyses and releases new phages.
Figure 10.1C
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10.2 DNA and RNA are polymers of nucleotides

• DNA is a nucleic acid, made of long chains of
  nucleotides

Phosphate group
Nitrogenous base
Nitrogenous base(A, G, C, or T)
Sugar
Phosphategroup
Nucleotide
Thymine (T)
Sugar(deoxyribose)
DNA nucleotide
Figure 10.2A
Polynucleotide
Sugar-phosphate backbone
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• DNA has four kinds of bases, A, T, C, and G

Thymine (T)
Cytosine (C)
Adenine (A)
Guanine (G)
Pyrimidines
Purines
Figure 10.2B
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• RNA is also a nucleic acid

• RNA has a slightly different sugar
• RNA has U instead of T

Nitrogenous base(A, G, C, or U)
Phosphategroup
Uracil (U)
Sugar(ribose)
Figure 10.2C, D
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10.3 DNA is a double-stranded helix

• James Watson and Francis Crick worked out the
  three-dimensional structure of DNA, based on work
  by Rosalind Franklin

Figure 10.3A, B
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• The structure of DNA consists of two
  polynucleotide strands wrapped around each other
  in a double helix

1 chocolate coat, Blind (PRA)
Figure 10.3C
Twist
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• Hydrogen bonds between bases hold the strands
  together

• Each base pairs with a complementary partner
• A pairs with T
• G pairs with C

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• Three representations of DNA

Hydrogen bond
Ribbon model
Partial chemical structure
Computer model
Figure 10.3D
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10.4 DNA replication depends on specific base
pairing
DNA REPLICATION

• In DNA replication, the strands separate
• Enzymes use each strand as a template to assemble
  the new strands

A
A
Nucleotides
Parental moleculeof DNA
Both parental strands serveas templates
Two identical daughtermolecules of DNA
Figure 10.4A
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• Untwisting and replication of DNA

Figure 10.4B
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10.5 DNA replication A closer look

• DNA replication begins at specific sites

Parental strand
Origin of replication
Daughter strand
Bubble
Two daughter DNA molecules
Figure 10.5A
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• Each strand of the double helix is oriented in
  the opposite direction

5? end
3? end
P
P
P
P
P
P
P
P
3? end
5? end
Figure 10.5B
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3?
DNA polymerasemolecule
5?

• How DNA daughter strands are synthesized

5? end
Daughter strandsynthesizedcontinuously
Parental DNA
5?
3?
Daughter strandsynthesizedin pieces
3?
P
5?

• The daughter strands are identical to the parent
  molecule

5?
P
3?
DNA ligase
Overall direction of replication
Figure 10.5C
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GENETIC INFORMATION FLOWS FROM DNA TO RNA TO
PROTEIN
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10.6 The DNA genotype is expressed as proteins,
which provide the molecular basis for phenotypic
traits
THE FLOW OF GENETIC INFORMATION FROM DNA TO RNA
TO PROTEIN

• The information constituting an organisms
  genotype is carried in its sequence of bases

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• A specific gene specifies a polypeptide

• The DNA is transcribed into RNA, which is
  translated into the polypeptide

DNA
TRANSCRIPTION
DNA
RNA
TRANSLATION
Protein
Figure 10.6A
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• Studies of inherited metabolic disorders first
  suggested that phenotype is expressed through
  proteins

• Studies of the bread mold Neurospora crassa led
  to the one gene-one polypeptide hypothesis

Figure 10.6B
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10.7 Genetic information written in codons is
translated into amino acid sequences

• The words of the DNA language are triplets of
  bases called codons
• The codons in a gene specify the amino acid
  sequence of a polypeptide

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Gene 1
Gene 3
DNA molecule
Gene 2
DNA strand
TRANSCRIPTION
RNA
Codon
TRANSLATION
Polypeptide
Amino acid
Figure 10.7
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10.8 The genetic code is the Rosetta stone of
life

• Virtually all organisms share the same genetic
  code

Figure 10.8A
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• An exercise in translating the genetic code

Transcribed strand
DNA
Transcription
RNA
Startcodon
Stopcodon
Translation
Polypeptide
Figure 10.8B
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10.9 Transcription produces genetic messages in
the form of RNA
RNA nucleotide
RNApolymerase
Direction oftranscription
Templatestrand of DNA
Newly made RNA
Figure 10.9A
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RNA polymerase

• In transcription, the DNA helix unzips

DNA of gene
Promoter DNA
Terminator DNA
Initiation

• RNA nucleotides line up along one strand of the
  DNA following the base-pairing rules
• The single-stranded messenger RNA peels away and
  the DNA strands rejoin

Elongation
Area shownin Figure 10.9A
Termination
GrowingRNA
Completed RNA
RNApolymerase
Figure 10.9B
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10.10 Eukaryotic RNA is processed before leaving
the nucleus

• Noncoding segments called introns are spliced out
• A cap and a tail are added to the ends

Exon
Intron
Intron
Exon
Exon
DNA
TranscriptionAddition of cap and tail
Cap
RNAtranscriptwith capand tail
Introns removed
Tail
Exons spliced together
mRNA
Coding sequence
NUCLEUS
CYTOPLASM
Figure 10.10
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10.11 Transfer RNA molecules serve as
interpreters during translation

• In the cytoplasm, a ribosome attaches to the mRNA
  and translates its message into a polypeptide
• The process is aided by transfer RNAs

Amino acid attachment site
Hydrogen bond
RNA polynucleotide chain
Anticodon
Figure 10.11A
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• Each tRNA molecule has a triplet anticodon on one
  end and an amino acid attachment site on the other

Amino acidattachment site
Anticodon
Figure 10.11B, C
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10.12 Ribosomes build polypeptides
Next amino acidto be added topolypeptide
Growingpolypeptide
tRNA molecules
P site
A site
Growingpolypeptide
Largesubunit
tRNA
P
A
mRNA
mRNAbindingsite
Codons
Smallsubunit
mRNA
Figure 10.12A-C
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10.13 An initiation codon marks the start of an
mRNA message
Start of genetic message
End
Figure 10.13A
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• mRNA, a specific tRNA, and the ribosome subunits
  assemble during initiation

Largeribosomalsubunit
Initiator tRNA
P site
A site
Startcodon
Small ribosomalsubunit
mRNA
1
2
Figure 10.13B
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10.14 Elongation adds amino acids to the
polypeptide chain until a stop codon terminates
translation

• The mRNA moves a codon at a time relative to the
  ribosome
• A tRNA pairs with each codon, adding an amino
  acid to the growing polypeptide

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Amino acid
Polypeptide
Asite
P site
Anticodon
mRNA
1
Codon recognition
mRNAmovement
Stopcodon
Newpeptidebond
2
Peptide bond formation
3
Translocation
Figure 10.14
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10.15 Review The flow of genetic information in
the cell is DNA?RNA?protein

• The sequence of codons in DNA spells out the
  primary structure of a polypeptide
• Polypeptides form proteins that cells and
  organisms use

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• Summary of transcription and translation

TRANSCRIPTION
DNA
Stage mRNA istranscribed from aDNA
template.
1
mRNA
RNApolymerase
Amino acid
TRANSLATION
Stage Each amino acid attaches to its
proper tRNA with the help of a specific enzyme
and ATP.
2
Enzyme
tRNA
Anticodon
Initiator tRNA
Stage Initiation of polypeptide synthesis
3
Largeribosomalsubunit
The mRNA, the first tRNA, and the ribosomal
subunits come together.
Smallribosomalsubunit
Start Codon
mRNA
Figure 10.15
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Newpeptidebondforming
Growing polypeptide
Stage Elongation
4
A succession of tRNAs add their amino acids to
the polypeptide chain as the mRNA is moved
through the ribosome, one codon at a time.
Codons
mRNA
Polypeptide
Stage Termination
5
The ribosome recognizes a stop codon. The
poly-peptide is terminated and released.
Stop
Codon
Figure 10.15 (continued)
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10.16 Mutations can change the meaning of genes

• Mutations are changes in the DNA base sequence
• These are caused by errors in DNA replication or
  by mutagens
• The change of a single DNA nucleotide causes
  sickle-cell disease

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Normal hemoglobin DNA
Mutant hemoglobin DNA
mRNA
mRNA
Normal hemoglobin
Sickle-cell hemoglobin
Glu
Val
Figure 10.16A
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• Types of mutations

NORMAL GENE
mRNA
Protein
Met
Lys
Phe
Gly
Ala
BASE SUBSTITUTION
Met
Lys
Phe
Ser
Ala
Missing
BASE DELETION
Met
Lys
Leu
Ala
His
Figure 10.16B
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VIRUSES
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bacteriophage
ruptured bacterial cell
how small are viruses?
Fig. 22.2, p. 355
1.5 µm
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The Viruses

• Non-cellular infectious agent
• Protein coat surrounding a nucleic acids core
• DNA or RNA
• Reproduce only inside a host cell

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STRUCTURE

• Helical
• Polyhedral
• Enveloped or non-enveloped
• Spiked
• Complex
• Bacteriophages

Polyhedral Virus
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• Tobacco mosaic virus

Figure 10.19x
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Enveloped virus

• Envelope is made mostly of membrane remnants from
  previously infected cell
• HIV is example

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Infectious Agents Smaller Than Viruses

• Prions
• Proteins
• Altered products of a gene
• Diseases
• Kuru
• Scrapie
• Creutzfeldt-Jakob disease

• Viriods
• Tight folds of RNA
• Plant diseases

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Some viruses kill their host in a lytic cycle
others integrate into the host's genome,
initiating a lysogenic cycle.
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Virulent viruses, multiply within infected cells,
eventually lysing (rupturing) them. When a virus
kills the infected host cell in which it is
replicating, the reproductive cycle is referred
to as a lytic cycle
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Many bacteriophages (and other viruses), do not
immediately kill the cells they infect, instead
integrating their nucleic acid into the genome of
the infected host cell. While residing there, it
is called a prophage, such as the lambda (l)
phage of Escherichia coli.
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The integration of a virus into a cellular genome
is called lysogeny. At a later time, the prophage
may exit the genome and initiate virus
replication. This sort of reproductive cycle,
involving a period of genome integration, is
called a lysogenic cycle. Viruses that become
stably integrated within the genome of their host
cells are called lysogenic viruses or temperate
viruses.
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10.17 Viral DNA may become part of the host
chromosome
VIRUSES GENES IN PACKAGES
Phage
Attachesto cell
Bacterialchromosome
Phage DNA
Cell lyses,releasing phages
Phage injects DNA
Many celldivisions
Occasionally a prophagemay leave the
bacterialchromosome
LYSOGENIC CYCLE
LYTIC CYCLE
Phage DNAcircularizes
Phagesassemble
Lysogenic bacteriumreproduces normally,replicati
ng the prophageat each cell division
Prophage
OR
New phage DNA andproteins are synthesized
Phage DNA inserts into the bacterialchromosome
by recombination
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Viruses can transform harmless bacteria into
deadly pathogens
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During the integrated portion of a lysogenic
reproductive cycle, virus genes are often
expressed. RNA polymerase reads them just as if
they were host genes, and sometimes expression of
these genes has an important effect on the host
cell, altering it in novel ways. The genetic
alteration of a cell's genome by the introduction
of foreign DNA is called transformation.
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• Cholera is caused by a virulent form of the
  usually harmless bacterium Vibrio cholerae.
• A bacteriophage infects V. cholarae and
  introduces a gene into the bacterial chomosomes
• The inserted gene s translated along with the
  rest of the host genes. The bacterial cell has
  undergone transformation
• The inserted gene encodes cholera toxin

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10.18 Connection Many viruses cause disease in
animals

• Many viruses have RNA, rather than DNA, as their
  genetic material
• Example flu viruses

Membranousenvelope
RNA
Proteincoat
Glycoprotein spike
Figure 10.18A
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Glycoprotein spike
VIRUS

• Some animal viruses steal a bit of the host
  cells membrane

Protein coat
Viral RNA(genome)
Envelope
Plasmamembraneof hostcell
Entry
1
Uncoating
2
Viral RNA(genome)
RNA synthesisby viral enzyme
3
Proteinsynthesis
RNA synthesis(other strand)
5
4
mRNA
Template
New viral genome
Newviral protein
Newviral proteins
6
Assembly
Exit
7
Figure 10.18B
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10.19 Connection Plant viruses are serious
agricultural pests

• Most plant viruses have RNA
• Example tobacco mosaic disease

Protein
RNA
Figure 10.19
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10.20 Connection Emerging viruses threaten
human health

• The deadly Ebola virus causes hemorrhagic fever
• Each virus is an enveloped thread of
  protein-coated RNA
• Hantavirus is another enveloped RNA virus

Figure 10.20A, B
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The Deer mouse was discovered to be the Hanta
virus vector
Figure 10.20Bx
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• HIV infection

Figure 10.22x1
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10.21 The AIDS virus makes DNA on an RNA template

• HIV is a retrovirus

Envelope
Glycoprotein
Proteincoat
RNA(two identicalstrands)
Reversetranscriptase
Figure 10.21A
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• Inside a cell, HIV uses its RNA as a template for
  making DNA to insert into the host chromosome

Viral RNA
CYTOPLASM
1
NUCLEUS
DNAstrand
ChromosomalDNA
2
3
ProvirusDNA
Double-strandedDNA
4
5
RNA
ViralRNAandproteins
6
Figure 10.21B
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Killer Flu Breakthrough Genome Sciences Centre
Sequences SARS Associated Corona Virus
http//www.sciencedaily.com/releases/2003/04/03041
4090112.htm
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Experts link SARS origin to livestockErin
Saylor, Daily Staff Reporter April 09, 2003
http//www.michigandaily.com/vnews/display.v/ART/2
003/04/09/3e93a8c3a3cb8
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10.22 Virus research and molecular genetics are
intertwined

• Virus studies help establish molecular genetics
• Molecular genetics helps us understand viruses
• such as HIV, seen here attacking a white blood
  cell

Figure 10.22