Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Molecular Basis of Inheritance
• Overview: Li...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Hereditary information
– Is encoded in the chem...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evidence That DNA Can Transform Bacteria
• The ro...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Griffith found that when he mixed heat-killed
r...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Griffith called the phenomenon transformation
B...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evidence That Viral DNA Can Program Cells
• Addit...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Viruses that infect bacteria, bacteriophages
– ...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Experiments showing that DNA is the genetic mater...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Additional Evidence That DNA Is the Genetic Mater...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Erwin Chargaff analyzed the base composition of...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Building a Structural Model of DNA: Scientific In...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 16.7a, c
C
T
A
A
T
CG
GC
A
C G
AT
AT
A T
T...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Franklin had concluded that DNA
– Was composed ...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
O
–
O O
OH
O
–
O
O
O
H2C
O
–
O
O
O
H2C
O
–
O
O
O
...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Watson and Crick reasoned that there must be
ad...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
N H O CH3
N
N
O
N
N
N
N H
Sugar
Sugar
Adenine (A)...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Many proteins work together in DNA replication
...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In DNA replication
– The parent molecule unwind...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 16.10 a–c
Conservative
model. The two
pare...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
DNA Replication: A Closer Look
• The copying of D...
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• A eukaryotic chromosome
– May have hundreds or ...
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Figure 16.13
New strand Template strand
5 end 3...
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• DNA polymerases add nucleotides
– Only to the f...
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• To elongate the other new strand of DNA, the
la...
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Parental DNA
DNA pol Ill elongates
DNA strands on...
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Priming DNA Synthesis
• DNA polymerases cannot in...
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• Only one primer is needed for synthesis of the
...
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Replication Animation****
Overall direction of re...
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Other Proteins That Assist DNA Replication
• Heli...
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Figure 16.16
Overall direction of replication
Lea...
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The DNA Replication Machine as a Stationary Compl...
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Proofreading and Repairing DNA
• DNA polymerases ...
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Figure 16.17
Nuclease
DNA
polymerase
DNA
ligase
A...
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Replicating the Ends of DNA Molecules
• The ends ...
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• Eukaryotic chromosomal DNA molecules
– Have at ...
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• If the chromosomes of germ cells became
shorter...
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From Gene to Protein
• The DNA inherited by an or...
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• The ribosome
– Is part of the cellular machiner...
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Genes specify proteins via transcription and tran...
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• Using genetic crosses
– They determined that th...
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CONCLUSION From the growth patterns of the mutant...
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• Beadle and Tatum developed the “one gene–
one e...
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Basic Principles of Transcription and Translation...
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• In prokaryotes
– Transcription and translation ...
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Prokaryote/Eukaryote differences animation
• In e...
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• Cells are governed by a cellular chain of
comma...
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• During transcription
– The gene determines the ...
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Cracking the Code
• A codon in messenger RNA
– Is...
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Molecular Components of Transcription
• RNA synth...
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Synthesis of an RNA Transcript
• The stages of tr...
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Elongation
RNA
polymerase
Non-template
strand of ...
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RNA Polymerase Binding and Initiation of Transcri...
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Elongation of the RNA Strand
• As RNA polymerase ...
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• Eukaryotic cells modify RNA after transcription...
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Alteration of mRNA Ends
• Each end of a pre-mRNA ...
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Split Genes and RNA Splicing
• RNA splicing
– Rem...
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• Is carried out by spliceosomes in some cases
Fi...
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• Proteins often have a modular architecture
– Co...
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• A cell translates an mRNA message into protein
...
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• Molecules of tRNA are not all identical
– Each ...
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The Structure and Function of Transfer RNA
A
C
C
...
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• A specific enzyme called an aminoacyl-tRNA
synt...
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Ribosomes
• Ribosomes
– Facilitate the specific c...
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• The ribosomal subunits
– Are constructed of pro...
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• The ribosome has three binding sites for tRNA
–...
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Figure 17.16c
Amino end Growing polypeptide
Next ...
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Building a Polypeptide
• We can divide translatio...
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Ribosome Association and Initiation of Translatio...
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Elongation of the Polypeptide Chain
• In the elon...
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Termination of Translation
• The final stage of t...
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Polyribosomes
• A number of ribosomes can transla...
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Protein Folding and Post-Translational Modificati...
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Targeting Polypeptides to Specific Locations
• Tw...
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• Proteins destined for the endomembrane
system o...
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Figure 17.21
Ribosome
mRNA
Signal
peptide
Signal-...
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• RNA plays multiple roles in the cell: a review
...
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• Types of RNA in a Eukaryotic Cell
Table 17.1
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• Comparing gene expression in prokaryotes and
eu...
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• In a eukaryotic cell
– The nuclear envelope sep...
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What is a gene? revisiting the question
• A gene
...
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• A summary of transcription and translation in a...
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• Point mutations can affect protein structure an...
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• The change of a single nucleotide in the DNA’s
...
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Types of Point Mutations
• Point mutations within...
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Substitutions
• A base-pair substitution
– Is the...
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Insertions and Deletions
• Insertions and deletio...
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Mutagens
• Spontaneous mutations
– Can occur duri...
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Dn ato protein

  1. 1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Molecular Basis of Inheritance • Overview: Life’s Operating Instructions • In 1953, James Watson and Francis Crick shook the world – With an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA Figure 16.1
  2. 2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Hereditary information – Is encoded in the chemical language of DNA and reproduced in all the cells of your body • It is the DNA program – That directs the development of many different types of traits
  3. 3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evidence That DNA Can Transform Bacteria • The role of DNA in heredity – Was first worked out by studying bacteria and the viruses that infect them • Frederick Griffith was studying Streptococcus pneumoniae – A bacterium that causes pneumonia in mammals • He worked with two strains of the bacterium – A pathogenic strain and a nonpathogenic strain
  4. 4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Griffith found that when he mixed heat-killed remains of the pathogenic strain – With living cells of the nonpathogenic strain, some of these living cells became pathogenic Bacteria of the “S” (smooth) strain of Streptococcus pneumoniae are pathogenic because they have a capsule that protects them from an animal’s defense system. Bacteria of the “R” (rough) strain lack a capsule and are nonpathogenic. Frederick Griffith injected mice with the two strains as shown below: Griffith concluded that the living R bacteria had been transformed into pathogenic S bacteria by an unknown, heritable substance from the dead S cells. EXPERIMENT RESULTS CONCLUSION Living S (control) cells Living R (control) cells Heat-killed (control) S cells Mixture of heat-killed S cells and living R cells Mouse dies Mouse healthy Mouse healthy Mouse dies Living S cells are found in blood sample. Figure 16.2
  5. 5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Griffith called the phenomenon transformation Bacteria of the “S” (smooth) strain of Streptococcus pneumoniae are pathogenic because they have a capsule that protects them from an animal’s defense system. Bacteria of the “R” (rough) strain lack a capsule and are nonpathogenic. Frederick Griffith injected mice with the two strains as shown below: Griffith concluded that the living R bacteria had been transformed into pathogenic S bacteria by an unknown, heritable substance from the dead S cells. EXPERIMENT RESULTS CONCLUSION Living S (control) cells Living R (control) cells Heat-killed (control) S cells Mixture of heat-killed S cells and living R cells Mouse dies Mouse healthy Mouse healthy Mouse dies Living S cells are found in blood sample. Figure 16.2
  6. 6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evidence That Viral DNA Can Program Cells • Additional evidence for DNA as the genetic material – Came from studies of a virus that infects bacteria
  7. 7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Viruses that infect bacteria, bacteriophages – Are widely used as tools by researchers in molecular genetics Figure 16.3 Phage head Tail Tail fiber DNA Bacterial cell 100nm
  8. 8. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Experiments showing that DNA is the genetic material of a phage (T2) • The Hershey and Chase experiment In their famous 1952 experiment, Alfred Hershey and Martha Chase used radioactive sulfur and phosphorus to trace the fates of the protein and DNA, respectively, of T2 phages that infected bacterial cells. Radioactivity (phage protein) in liquid Phage Bacterial cell Radioactive protein Empty protein shell Phage DNA DNA Centrifuge Pellet (bacterial cells and contents) Radioactive DNA Centrifuge Pellet Batch 1: Phages were grown with radioactive sulfur (35 S), which was incorporated into phage protein (pink). Batch 2: Phages were grown with radioactive phosphorus (32 P), which was incorporated into phage DNA (blue). 1 2 3 4Agitated in a blender to separate phages outside the bacteria from the bacterial cells. Mixed radioactively labeled phages with bacteria. The phages infected the bacterial cells. Centrifuged the mixture so that bacteria formed a pellet at the bottom of the test tube. Measured the radioactivity in the pellet and the liquid Phage proteins remained outside the bacterial cells during infection, while phage DNA entered the cells. When cultured, bacterial cells with radioactive phage DNA released new phages with some radioactive phosphorus. Hershey and Chase concluded that DNA, not protein, functions as the T2 phage’s genetic material. RESULTS CONCLUSION EXPERIMENT Radioactivity (phage DNA) in pellet Figure 16.4 Animation of experiment
  9. 9. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Additional Evidence That DNA Is the Genetic Materia • Prior to the 1950s, it was already known that DNA – Is a polymer of nucleotides, each consisting of three components: a nitrogenous base, a sugar, and a phosphate group Sugar-phosphate backbone Nitrogenous bases 5 end O– O P O CH2 5 4O– H H O H H H 3 1 H O CH3 N O N H Thymine (T) O O P O O– CH2 H H O H H H H N N N H N H H Adenine (A) O O P O O– CH2 H H O H H H H H H HN NN O Cytosine (C) O O P O CH2 5 4O– H O H H 3 1 OH 2 H N N N H O N N HH H H Sugar (deoxyribose) 3 end Phosphate Guanine (G) DNA nucleotide 2 N Figure 16.5
  10. 10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Erwin Chargaff analyzed the base composition of DNA – From a number of different organisms • In 1947, Chargaff reported – That DNA composition varies from one species to the next • This evidence of molecular diversity among species – Made DNA a more credible candidate for the genetic material
  11. 11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Building a Structural Model of DNA: Scientific Inquiry • Maurice Wilkins and Rosalind Franklin – Were using a technique called X-ray crystallography to study molecular structure • Rosalind Franklin – Produced a picture of the DNA molecule using this technique (a) Rosalind Franklin Franklin’s X-ray diffraction Photograph of DNA (b) Figure 16.6 a, b
  12. 12. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.7a, c C T A A T CG GC A C G AT AT A T TA C TA 0.34 nm 3.4 nm (a) Key features of DNA structure G 1 nm G (c) Space-filling model T • Watson and Crick deduced that DNA was a double helix – Through observations of the X-ray crystallographic images of DNA
  13. 13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Franklin had concluded that DNA – Was composed of two antiparallel sugar- phosphate backbones, with the nitrogenous bases paired in the molecule’s interior • The nitrogenous bases – Are paired in specific combinations: adenine with thymine, and cytosine with guanine
  14. 14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings O – O O OH O – O O O H2C O – O O O H2C O – O O O OH O O O T A C GC A T O O O CH2 O O– O O CH2 CH2 CH2 5 end Hydrogen bond 3 end 3 end G P P P P O OH O– O O O P P O– O O O P O– O O O P (b) Partial chemical structure H2C 5 endFigure 16.7b O
  15. 15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Watson and Crick reasoned that there must be additional specificity of pairing – Dictated by the structure of the bases • Each base pair forms a different number of hydrogen bonds – Adenine and thymine form two bonds, cytosine and guanine form three bonds
  16. 16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings N H O CH3 N N O N N N N H Sugar Sugar Adenine (A) Thymine (T) N N N N Sugar O H N H NH N OH H N Sugar Guanine (G) Cytosine (C)Figure 16.8 H
  17. 17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Many proteins work together in DNA replication and repair (DNA-Protein like Chicken-Egg debate, which came first?) • Since the two strands of DNA are complementary – Each strand acts as a template for building a new strand in replication
  18. 18. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In DNA replication – The parent molecule unwinds, and two new daughter strands are built based on base- pairing rules (a) The parent molecule has two complementary strands of DNA. Each base is paired by hydrogen bonding with its specific partner, A with T and G with C. (b) The first step in replication is separation of the two DNA strands. (c) Each parental strand now serves as a template that determines the order of nucleotides along a new, complementary strand. (d) The nucleotides are connected to form the sugar-phosphate backbones of the new strands. Each “daughter” DNA molecule consists of one parental strand and one new strand. A C T A G A C T A G A C T A G A C T A G T G A T C T G A T C A C T A G A C T A G T G A T C T G A T C T G A T C T G A T C Figure 16.9 a–d
  19. 19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.10 a–c Conservative model. The two parental strands reassociate after acting as templates for new strands, thus restoring the parental double helix. Semiconservative model. The two strands of the parental molecule separate, and each functions as a template for synthesis of a new, comple- mentary strand. Dispersive model. Each strand of both daughter mol- ecules contains a mixture of old and newly synthesized DNA. Parent cell First replication Second replication • DNA replication is semiconservative – Each of the two new daughter molecules will have one old strand, derived from the parent molecule, and one newly made strand (a) (b) (c)
  20. 20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA Replication: A Closer Look • The copying of DNA – Is remarkable in its speed and accuracy • More than a dozen enzymes and other proteins – Participate in DNA replication • The replication of a DNA molecule – Begins at special sites called origins of replication, where the two strands are separated
  21. 21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • A eukaryotic chromosome – May have hundreds or even thousands of replication origins Replication begins at specific sites where the two parental strands separate and form replication bubbles. The bubbles expand laterally, as DNA replication proceeds in both directions. Eventually, the replication bubbles fuse, and synthesis of the daughter strands is complete. 1 2 3 Origin of replication Bubble Parental (template) strand Daughter (new) strand Replication fork Two daughter DNA molecules In eukaryotes, DNA replication begins at many sites along the giant DNA molecule of each chromosome. In this micrograph, three replication bubbles are visible along the DNA of a cultured Chinese hamster cell (TEM). (b)(a) 0.25 µm Figure 16.12 a, b
  22. 22. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.13 New strand Template strand 5 end 3 end Sugar A T Base C G G C A C T P P P OH P P 5 end 3 end 5 end 5 end A T C G G C A C T 3 endPyrophosphate 2 P OH Phosphate Elongating a New DNA Strand • Elongation of new DNA at a replication fork – Is catalyzed by enzymes called DNA polymerases, which add nucleotides to the 3′ end of a growing strand Nucleoside triphosphate
  23. 23. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • DNA polymerases add nucleotides – Only to the free 3′ end of a growing strand • Along one template strand of DNA, the leading strand – DNA polymerase III can synthesize a complementary strand continuously, moving toward the replication fork
  24. 24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • To elongate the other new strand of DNA, the lagging strand – DNA polymerase III must work in the direction away from the replication fork • The lagging strand – Is synthesized as a series of segments called Okazaki fragments, which are then joined together by DNA ligase
  25. 25. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Parental DNA DNA pol Ill elongates DNA strands only in the 5 3 direction. 1 Okazaki fragments DNA pol III Template strand Lagging strand 3 2 Template strand DNA ligase Overall direction of replication One new strand, the leading strand, can elongate continuously 5 3 as the replication fork progresses. 2 The other new strand, the lagging strand must grow in an overall 3 5 direction by addition of short segments, Okazaki fragments, that grow 5 3 (numbered here in the order they were made). 3 DNA ligase joins Okazaki fragments by forming a bond between their free ends. This results in a continuous strand. 4 Figure 16.14 3 5 5 3 3 5 2 1 Leading strand 1 • Synthesis of leading and lagging strands during DNA replication
  26. 26. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Priming DNA Synthesis • DNA polymerases cannot initiate the synthesis of a polynucleotide – They can only add nucleotides to the 3′ end • The initial nucleotide strand – Is an RNA or DNA primer
  27. 27. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Only one primer is needed for synthesis of the leading strand – But for synthesis of the lagging strand, each Okazaki fragment must be primed separately
  28. 28. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Replication Animation**** Overall direction of replication 3 3 3 3 5 3 5 3 5 3 5 3 5 3 5 3 5 3 5 5 1 1 2 1 1 2 5 5 1 2 35 Template strand RNA primer Okazaki fragment Figure 16.15 Primase joins RNA nucleotides into a primer. 1 DNA pol III adds DNA nucleotides to the primer, forming an Okazaki fragment. 2 After reaching the next RNA primer (not shown), DNA pol III falls off. 3 After the second fragment is primed. DNA pol III adds DNA nucleotides until it reaches the first primer and falls off. 4 DNA pol 1 replaces the RNA with DNA, adding to the 3 end of fragment 2. 5 DNA ligase forms a bond between the newest DNA and the adjacent DNA of fragment 1. 6 The lagging strand in this region is now complete. 7
  29. 29. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Other Proteins That Assist DNA Replication • Helicase, topoisomerase, single-strand binding protein – Are all proteins that assist DNA replication Table 16.1
  30. 30. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.16 Overall direction of replication Leading strand Lagging strand Lagging strand Leading strandOVERVIEW Leading strand Replication fork DNA pol III Primase Primer DNA pol III Lagging strand DNA pol I Parental DNA 5 3 4 3 2 Origin of replication DNA ligase 1 5 3 Helicase unwinds the parental double helix. 1 Molecules of single- strand binding protein stabilize the unwound template strands. 2 The leading strand is synthesized continuously in the 5 3 direction by DNA pol III. 3 Primase begins synthesis of RNA primer for fifth Okazaki fragment. 4 DNA pol III is completing synthesis of the fourth fragment, when it reaches the RNA primer on the third fragment, it will dissociate, move to the replication fork, and add DNA nucleotides to the 3 end of the fifth fragment primer. 5 DNA pol I removes the primer from the 5 end of the second fragment, replacing it with DNA nucleotides that it adds one by one to the 3 end of the third fragment. The replacement of the last RNA nucleotide with DNA leaves the sugar- phosphate backbone with a free 3 end. 6 DNA ligase bonds the 3 end of the second fragment to the 5 end of the first fragment. 7 Replication Animation #2 Recap • A summary of DNA replication
  31. 31. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The DNA Replication Machine as a Stationary Complex • The various proteins that participate in DNA replication – Form a single large complex, a DNA replication “machine” • The DNA replication machine – Is probably stationary during the replication process
  32. 32. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Proofreading and Repairing DNA • DNA polymerases proofread newly made DNA – Replacing any incorrect nucleotides • In mismatch repair of DNA – Repair enzymes correct errors in base pairing
  33. 33. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.17 Nuclease DNA polymerase DNA ligase A thymine dimer distorts the DNA molecule. 1 A nuclease enzyme cuts the damaged DNA strand at two points and the damaged section is removed. 2 Repair synthesis by a DNA polymerase fills in the missing nucleotides. 3 DNA ligase seals the Free end of the new DNA To the old DNA, making the strand complete. 4 • In nucleotide excision repair – Enzymes cut out and replace damaged stretches of DNA
  34. 34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Replicating the Ends of DNA Molecules • The ends of eukaryotic chromosomal DNA – Get shorter with each round of replication Figure 16.18 End of parental DNA strands Leading strand Lagging strand Last fragment Previous fragment RNA primer Lagging strand Removal of primers and replacement with DNA where a 3 end is available Primer removed but cannot be replaced with DNA because no 3 end available for DNA polymerase Second round of replication New leading strand New lagging strand 5 Further rounds of replication Shorter and shorter daughter molecules 5 3 5 3 5 3 5 3 3
  35. 35. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Eukaryotic chromosomal DNA molecules – Have at their ends nucleotide sequences, called telomeres, that postpone the erosion of genes near the ends of DNA molecules Figure 16.19 1 µm
  36. 36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • If the chromosomes of germ cells became shorter in every cell cycle – Essential genes would eventually be missing from the gametes they produce • An enzyme called telomerase – Catalyzes the lengthening of telomeres in germ cells
  37. 37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings From Gene to Protein • The DNA inherited by an organism – Leads to specific traits by dictating the synthesis of proteins • The process by which DNA directs protein synthesis, gene expression – Includes two stages, called transcription and translation
  38. 38. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The ribosome – Is part of the cellular machinery for translation, polypeptide synthesis Figure 17.1
  39. 39. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Genes specify proteins via transcription and translation • In 1909, British physician Archibald Garrod – Was the first to suggest that genes dictate phenotypes through enzymes that catalyze specific chemical reactions in the cell • Beadle and Tatum causes bread mold to mutate with X-rays – Creating mutants that could not survive on minimal medium
  40. 40. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Using genetic crosses – They determined that their mutants fell into three classes, each mutated in a different gene Figure 17.2 Working with the mold Neurospora crassa, George Beadle and Edward Tatum had isolated mutants requiring arginine in their growth medium and had shown genetically that these mutants fell into three classes, each defective in a different gene. From other considerations, they suspected that the metabolic pathway of arginine biosynthesis included the precursors ornithine and citrulline. Their most famous experiment, shown here, tested both their one gene–one enzyme hypothesis and their postulated arginine pathway. In this experiment, they grew their three classes of mutants under the four different conditions shown in the Results section below. The wild-type strain required only the minimal medium for growth. The three classes of mutants had different growth requirements EXPERIMENT RESULTS Class I Mutants Class II Mutants Class III MutantsWild type Minimal medium (MM) (control) MM + Ornithine MM + Citrulline MM + Arginine (control)
  41. 41. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings CONCLUSION From the growth patterns of the mutants, Beadle and Tatum deduced that each mutant was unable to carry out one step in the pathway for synthesizing arginine, presumably because it lacked the necessary enzyme. Because each of their mutants was mutated in a single gene, they concluded that each mutated gene must normally dictate the production of one enzyme. Their results supported the one gene–one enzyme hypothesis and also confirmed the arginine pathway. (Notice that a mutant can grow only if supplied with a compound made after the defective step.) Class I Mutants (mutation in gene A) Class II Mutants (mutation in gene B) Class III Mutants (mutation in gene C)Wild type Gene A Gene B Gene C Precursor Precursor Precursor Precursor Ornithine Ornithine Ornithine Ornithine Citrulline Citrulline Citrulline Citrulline Arginine Arginine Arginine Arginine Enzyme A Enzyme B Enzyme C A A A B B B C C C
  42. 42. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Beadle and Tatum developed the “one gene– one enzyme hypothesis” – Which states that the function of a gene is to dictate the production of a specific enzyme • As researchers learned more about proteins – They made minor revision to the one gene– one enzyme hypothesis • Genes code for polypeptide chains or for RNA molecules
  43. 43. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Basic Principles of Transcription and Translation • Transcription – Is the synthesis of RNA under the direction of DNA – Produces messenger RNA (mRNA) • Translation – Is the actual synthesis of a polypeptide, which occurs under the direction of mRNA – Occurs on ribosomes http://vcell.ndsu.nodak.edu/animations/ transcription/index.htm - animations
  44. 44. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In prokaryotes – Transcription and translation occur together Figure 17.3a Prokaryotic cell. In a cell lacking a nucleus, mRNA produced by transcription is immediately translated without additional processing. (a) TRANSLATION TRANSCRIPTION DNA mRNA Ribosome Polypeptide
  45. 45. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Prokaryote/Eukaryote differences animation • In eukaryotes – RNA transcripts are modified before becoming true mRNA Figure 17.3b Eukaryotic cell. The nucleus provides a separate compartment for transcription. The original RNA transcript, called pre-mRNA, is processed in various ways before leaving the nucleus as mRNA. (b) TRANSCRIPTION RNA PROCESSING TRANSLATION mRNA DNA Pre-mRNA Polypeptide Ribosome Nuclear envelope
  46. 46. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Cells are governed by a cellular chain of command – DNA → RNA → protein • Genetic information – Is encoded as a sequence of nonoverlapping base triplets, or codons
  47. 47. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • During transcription – The gene determines the sequence of bases along the length of an mRNA molecule Figure 17.4 DNA molecule Gene 1 Gene 2 Gene 3 DNA strand (template) TRANSCRIPTION mRNA Protein TRANSLATION Amino acid A C C A A A C C G A G T U G G U U U G G C U C A Trp Phe Gly Ser Codon 3 5 35
  48. 48. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Cracking the Code • A codon in messenger RNA – Is either translated into an amino acid or serves as a translational stop signal Second mRNA base U C A G U C A G UUU UUC UUA UUG CUU CUC CUA CUG AUU AUC AUA AUG GUU GUC GUA GUG Met or start Phe Leu Leu lle Val UCU UCC UCA UCG CCU CCC CCA CCG ACU ACC ACA ACG GCU GCC GCA GCG Ser Pro Thr Ala UAU UAC UGU UGC Tyr Cys CAU CAC CAA CAG CGU CGC CGA CGG AAU AAC AAA AAG AGU AGC AGA AGG GAU GAC GAA GAG GGU GGC GGA GGG UGG UAA UAG Stop Stop UGA Stop Trp His Gln Asn Lys Asp Arg Ser Arg Gly U C A G U C A G U C A G U C A G FirstmRNAbase(5end) ThirdmRNAbase(3end) Glu Codons must be read in the correct reading frame For the specified polypeptide to be produced
  49. 49. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Molecular Components of Transcription • RNA synthesis – Is catalyzed by RNA polymerase, which pries the DNA strands apart and hooks together the RNA nucleotides – Follows the same base-pairing rules as DNA, except that in RNA, uracil substitutes for thymine
  50. 50. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Synthesis of an RNA Transcript • The stages of transcription are – Initiation – Elongation – Termination Figure 17.7 Promoter Transcription unit RNA polymerase Start point 5 3 3 5 3 5 5 3 5 3 3 5 5 3 3 5 5 5 Rewound RNA RNA transcript 3 3 Completed RNA transcript Unwound DNA RNA transcript Template strand of DNA DNA 1 Initiation. After RNA polymerase binds to the promoter, the DNA strands unwind, and the polymerase initiates RNA synthesis at the start point on the template strand. 2 Elongation. The polymerase moves downstream, unwinding the DNA and elongating the RNA transcript 5  3 . In the wake of transcription, the DNA strands re-form a double helix. 3 Termination. Eventually, the RNA transcript is released, and the polymerase detaches from the DNA.
  51. 51. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Elongation RNA polymerase Non-template strand of DNA RNA nucleotides 3 end C A E G C A A U T A G G T T A A C G U A T C A T C C A A T T G G 3 5 5 Newly made RNA Direction of transcription (“downstream”) Template strand of DNA
  52. 52. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings RNA Polymerase Binding and Initiation of Transcription • Promoters signal the initiation of RNA synthesis • Transcription factors – Help eukaryotic RNA polymerase recognize promoter sequences Figure 17.8Figure 17.8 TRANSCRIPTION RNA PROCESSING TRANSLATION DNA Pre-mRNA mRNA Ribosome Polypeptide T A T AAA A ATAT T T T TATA box Start point Template DNA strand 5 3 3 5 Transcription factors 5 3 3 5 Promoter 5 3 3 55 RNA polymerase II Transcription factors RNA transcript Transcription initiation complex Eukaryotic promoters1 Several transcription factors 2 Additional transcription factors 3
  53. 53. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Elongation of the RNA Strand • As RNA polymerase moves along the DNA – It continues to untwist the double helix, exposing about 10 to 20 DNA bases at a time for pairing with RNA nucleotides • The mechanisms of termination – Are different in prokaryotes and eukaryotes
  54. 54. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Eukaryotic cells modify RNA after transcription • Enzymes in the eukaryotic nucleus – Modify pre-mRNA in specific ways before the genetic messages are dispatched to the cytoplasm
  55. 55. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Alteration of mRNA Ends • Each end of a pre-mRNA molecule is modified in a particular way – The 5′ end receives a modified nucleotide cap – The 3′ end gets a poly-A tail Figure 17.9 A modified guanine nucleotide added to the 5 end 50 to 250 adenine nucleotides added to the 3 end Protein-coding segment Polyadenylation signal Poly-A tail3 UTR Stop codonStart codon 5 Cap 5 UTR AAUAAA AAA…AAA TRANSCRIPTION RNA PROCESSING DNA Pre-mRNA mRNA TRANSLATION Ribosome Polypeptide G P P P 5 3 Video clip
  56. 56. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Split Genes and RNA Splicing • RNA splicing – Removes introns (supposed “Junk-DNA”) and joins exons Figure 17.10 TRANSCRIPTION RNA PROCESSING DNA Pre-mRNA mRNA TRANSLATION Ribosome Polypeptide 5 Cap Exon Intron 1 5 30 31 Exon Intron 104 105 146 Exon 3 Poly-A tail Poly-A tail Introns cut out and exons spliced together Coding segment 5 Cap 1 146 3 UTR3 UTR Pre-mRNA mRNA
  57. 57. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Is carried out by spliceosomes in some cases Figure 17.11 RNA transcript (pre-mRNA) Exon 1 Intron Exon 2 Other proteins Protein snRNA snRNPs Spliceosome Spliceosome components Cut-out intron mRNA Exon 1 Exon 2 5 5 5 1 2 3 Animation Ribozymes Are catalytic RNA molecules that function as enzymes and can splice RNA
  58. 58. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Proteins often have a modular architecture – Consisting of discrete structural and functional regions called domains • In many cases – Different exons code for the different domains in a protein Figure 17.12 Gene DNA Exon 1 Intron Exon 2 Intron Exon 3 Transcription RNA processing Translation Domain 3 Domain 1 Domain 2 Polypeptide
  59. 59. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • A cell translates an mRNA message into protein – With the help of transfer RNA (tRNA) Figure 17.13 TRANSCRIPTION TRANSLATION DNA mRNA Ribosome Polypeptide Polypeptide Amino acids tRNA with amino acid attachedRibosome tRNA Anticodon mRNA Trp Phe Gly A G C A A A C C G U G G U U U G G C Codons5 3
  60. 60. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Molecules of tRNA are not all identical – Each carries a specific amino acid on one end – Each has an anticodon on the other end (b) Three-dimensional structure Symbol used in this book Amino acid attachment site Hydrogen bonds Anticodon Anticodon A AG 5 3 3 5 (c)
  61. 61. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Structure and Function of Transfer RNA A C C • A tRNA molecule – Consists of a single RNA strand that is only about 80 nucleotides long Figure 17.14a Two-dimensional structure. The four base-paired regions and three loops are characteristic of all tRNAs, as is the base sequence of the amino acid attachment site at the 3 end. The anticodon triplet is unique to each tRNA type. (The asterisks mark bases that have been chemically modified, a characteristic of tRNA.) (a) 3 C C A C G C U U A A GACAC CU * G C * * G U G U *CU * G AG G U * *A * A A G U C A G A C C * C G A G A G G G * * GA CUC*A U U U A G G C G 5 Amino acid attachment site Hydrogen bonds Anticodon A
  62. 62. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • A specific enzyme called an aminoacyl-tRNA synthetase – Joins each amino acid to the correct tRNA Figure 17.15 Amino acid ATP Adenosine Pyrophosphate Adenosine Adenosine Phosphates tRNA P P P P P Pi Pi Pi P AMP Aminoacyl tRNA (an “activated amino acid”) Aminoacyl-tRNA synthetase (enzyme) Active site binds the amino acid and ATP. 1 ATP loses two P groups and joins amino acid as AMP. 2 3 Appropriate tRNA covalently Bonds to amino Acid, displacing AMP. Activated amino acid is released by the enzyme. 4
  63. 63. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ribosomes • Ribosomes – Facilitate the specific coupling of tRNA anticodons with mRNA codons during protein synthesis
  64. 64. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The ribosomal subunits – Are constructed of proteins and RNA molecules named ribosomal RNA or rRNA Figure 17.16a TRANSCRIPTION TRANSLATION DNA mRNA Ribosome Polypeptide Exit tunnel Growing polypeptide tRNA molecules E P A Large subunit Small subunit mRNA Computer model of functioning ribosome. This is a model of a bacterial ribosome, showing its overall shape. The eukaryotic ribosome is roughly similar. A ribosomal subunit is an aggregate of ribosomal RNA molecules and proteins. (a) 5 3
  65. 65. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The ribosome has three binding sites for tRNA – The P site – The A site – The E site Figure 17.16b E P A P site (Peptidyl-tRNA binding site) E site (Exit site) mRNA binding site A site (Aminoacyl- tRNA binding site) Large subunit Small subunit Schematic model showing binding sites. A ribosome has an mRNA binding site and three tRNA binding sites, known as the A, P, and E sites. This schematic ribosome will appear in later diagrams. (b)
  66. 66. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 17.16c Amino end Growing polypeptide Next amino acid to be added to polypeptide chain tRNA mRNA Codons 3 5 Schematic model with mRNA and tRNA. A tRNA fits into a binding site when its anticodon base-pairs with an mRNA codon. The P site holds the tRNA attached to the growing polypeptide. The A site holds the tRNA carrying the next amino acid to be added to the polypeptide chain. Discharged tRNA leaves via the E site. (c)
  67. 67. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Building a Polypeptide • We can divide translation into three stages – Initiation – Elongation – Termination
  68. 68. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Ribosome Association and Initiation of Translation • The initiation stage of translation – Brings together mRNA, tRNA bearing the first amino acid of the polypeptide, and two subunits of a ribosome Large ribosomal subunit The arrival of a large ribosomal subunit completes the initiation complex. Proteins called initiation factors (not shown) are required to bring all the translation components together. GTP provides the energy for the assembly. The initiator tRNA is in the P site; the A site is available to the tRNA bearing the next amino acid. 2 Initiator tRNA mRNA mRNA binding site Small ribosomal subunit Translation initiation complex P site GDPGTP Start codon A small ribosomal subunit binds to a molecule of mRNA. In a prokaryotic cell, the mRNA binding site on this subunit recognizes a specific nucleotide sequence on the mRNA just upstream of the start codon. An initiator tRNA, with the anticodon UAC, base-pairs with the start codon, AUG. This tRNA carries the amino acid methionine (Met). 1 Met Met U A C A U G E A 3 5 5 3 35 35 Figure 17.17
  69. 69. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Elongation of the Polypeptide Chain • In the elongation stage of translation – Amino acids are added one by one to the preceding amino acid Figure 17.18 Amino end of polypeptide mRNA Ribosome ready for next aminoacyl tRNA E P A E P A E P A E P A GDP GTP GTP GDP 2 2 site site5 3 TRANSCRIPTION TRANSLATION DNA mRNA Ribosome Polypeptide Codon recognition. The anticodon of an incoming aminoacyl tRNA base-pairs with the complementary mRNA codon in the A site. Hydrolysis of GTP increases the accuracy and efficiency of this step. 1 Peptide bond formation. An rRNA molecule of the large subunit catalyzes the formation of a peptide bond between the new amino acid in the A site and the carboxyl end of the growing polypeptide in the P site. This step attaches the polypeptide to the tRNA in the A site. 2 Translocation. The ribosome translocates the tRNA in the A site to the P site. The empty tRNA in the P site is moved to the E site, where it is released. The mRNA moves along with its bound tRNAs, bringing the next codon to be translated into the A site. 3
  70. 70. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Termination of Translation • The final stage of translation is termination – When the ribosome reaches a stop codon in the mRNA Figure 17.19 Release factor Free polypeptide Stop codon (UAG, UAA, or UGA) 5 3 3 5 3 5 When a ribosome reaches a stop codon on mRNA, the A site of the ribosome accepts a protein called a release factor instead of tRNA. 1 The release factor hydrolyzes the bond between the tRNA in the P site and the last amino acid of the polypeptide chain. The polypeptide is thus freed from the ribosome. 2 3 The two ribosomal subunits and the other components of the assembly dissociate. Protein Synthesis Animation
  71. 71. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Polyribosomes • A number of ribosomes can translate a single mRNA molecule simultaneously – Forming a polyribosome Figure 17.20a, b Growing polypeptides Completed polypeptide Incoming ribosomal subunits Start of mRNA (5 end) End of mRNA (3 end) Polyribosome An mRNA molecule is generally translated simultaneously by several ribosomes in clusters called polyribosomes. (a) Ribosomes mRNA This micrograph shows a large polyribosome in a prokaryotic cell (TEM). 0.1 µm (b)
  72. 72. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Protein Folding and Post-Translational Modifications • After translation – Proteins may be modified in ways that affect their three-dimensional shape
  73. 73. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Targeting Polypeptides to Specific Locations • Two populations of ribosomes are evident in cells – Free and bound • Free ribosomes in the cytosol – Initiate the synthesis of all proteins
  74. 74. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Proteins destined for the endomembrane system or for secretion – Must be transported into the ER – Have signal peptides to which a signal- recognition particle (SRP) binds, enabling the translation ribosome to bind to the ER
  75. 75. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 17.21 Ribosome mRNA Signal peptide Signal- recognition particle (SRP) SRP receptor protein Translocation complex CYTOSOL Signal peptide removed ER membrane Protein ERLUMEN • The signal mechanism for targeting proteins to the ER Polypeptide synthesis begins on a free ribosome in the cytosol. 1 An SRP binds to the signal peptide, halting synthesis momentarily. 2 The SRP binds to a receptor protein in the ER membrane. This receptor is part of a protein complex (a translocation complex) that has a membrane pore and a signal-cleaving enzyme. 3 The SRP leaves, and the polypeptide resumes growing, meanwhile translocating across the membrane. (The signal peptide stays attached to the membrane.) 4 The signal- cleaving enzyme cuts off the signal peptide. 5 The rest of the completed polypeptide leaves the ribosome and folds into its final conformation. 6
  76. 76. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • RNA plays multiple roles in the cell: a review • RNA – Can hydrogen-bond to other nucleic acid molecules – Can assume a specific three-dimensional shape – Has functional groups that allow it to act as a catalyst
  77. 77. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Types of RNA in a Eukaryotic Cell Table 17.1
  78. 78. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Comparing gene expression in prokaryotes and eukaryotes reveals key differences • Prokaryotic cells lack a nuclear envelope – Allowing translation to begin while transcription is still in progress Figure 17.22 DNA Polyribosome mRNA Direction of transcription 0.25 mRNA polymerase Polyribosome Ribosome DNA mRNA (5 end) RNA polymerase Polypeptide (amino end)
  79. 79. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • In a eukaryotic cell – The nuclear envelope separates transcription from translation – Extensive RNA processing occurs in the nucleus
  80. 80. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings What is a gene? revisiting the question • A gene – Is a region of DNA whose final product is either a polypeptide or an RNA molecule
  81. 81. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • A summary of transcription and translation in a eukaryotic cell Figure 17.26 TRANSCRIPTION RNA is transcribed from a DNA template. DNA RNA polymerase RNA transcript RNA PROCESSING In eukaryotes, the RNA transcript (pre- mRNA) is spliced and modified to produce mRNA, which moves from the nucleus to the cytoplasm. Exon Poly-A RNA transcript (pre-mRNA) Intron NUCLEUS Cap FORMATION OF INITIATION COMPLEX After leaving the nucleus, mRNA attaches to the ribosome. CYTOPLASM mRNA Poly-A Growing polypeptide Ribosomal subunits Cap Aminoacyl-tRNA synthetase Amino acid tRNA AMINO ACID ACTIVATION Each amino acid attaches to its proper tRNA with the help of a specific enzyme and ATP. Activated amino acid TRANSLATION 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. (When completed, the polypeptide is released from the ribosome.) Anticodon A CC A A A UG GUU UA U G UACE A Ribosome 1 Poly-A 5 5 3 Codon 2 3 4 5
  82. 82. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • Point mutations can affect protein structure and function • Mutations – Are changes in the genetic material of a cell • Point mutations – Are changes in just one base pair of a gene
  83. 83. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings • The change of a single nucleotide in the DNA’s template strand – Leads to the production of an abnormal protein Figure 17.23 In the DNA, the mutant template strand has an A where the wild-type template has a T. The mutant mRNA has a U instead of an A in one codon. The mutant (sickle-cell) hemoglobin has a valine (Val) instead of a glutamic acid (Glu). Mutant hemoglobin DNAWild-type hemoglobin DNA mRNA mRNA Normal hemoglobin Sickle-cell hemoglobin Glu Val C T T C A T G A A G U A 3 5 3 5 5 35 3
  84. 84. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Types of Point Mutations • Point mutations within a gene can be divided into two general categories – Base-pair substitutions – Base-pair insertions or deletions (indels)
  85. 85. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Substitutions • A base-pair substitution – Is the replacement of one nucleotide and its partner with another pair of nucleotides – Can cause missense or nonsense Figure 17.24 Wild type A U G A A G U U U G G C U A A mRNA 5 Protein Met Lys Phe Gly Stop Carboxyl end Amino end 3 A U G A A G U U U G G U U A A Met Lys Phe Gly Base-pair substitution No effect on amino acid sequence U instead of C Stop A U G A A G U U U A G U U A A Met Lys Phe Ser Stop A U G U A G U U U G G C U A A Met Stop Missense A instead of G Nonsense U instead of A
  86. 86. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Insertions and Deletions • Insertions and deletions – Are additions or losses of nucleotide pairs in a gene – May produce frameshift mutations Figure 17.25 mRNA Protein Wild type A U G A A G U U U G G C U A A 5 Met Lys Phe Gly Amino end Carboxyl end Stop Base-pair insertion or deletion Frameshift causing immediate nonsense A U G U A A G U U U G G C U A A U G A A G U U G G C U A A A U G U U U G G C U A A Met Stop U Met Lys Leu Ala Met Phe Gly Stop MissingA A G Missing Extra U Frameshift causing extensive missense Insertion or deletion of 3 nucleotides: no frameshift but extra or missing amino acid 3
  87. 87. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Mutagens • Spontaneous mutations – Can occur during DNA replication, recombination, or repair • Mutagens – Are physical or chemical agents that can cause mutations
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