1. The Molecular Basis of Inheritance
Chapter 16
The Molecular Basis of Inheritance

2. Overview: Life’s Operating Instructions
In 1953, James Watson and Francis Crick introduced an elegant double-helical model for the structure of deoxyribonucleic acid, or DNA
DNA, the substance of inheritance, is the most celebrated molecule of our time
Hereditary information is encoded in DNA and reproduced in all cells of the body
This DNA program directs the development of biochemical, anatomical, physiological, and (to some extent) behavioral traits
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3. Fig. 16-1
Figure 16.1 How was the structure of DNA determined?

4. Concept 16.1: DNA is the genetic material
Early in the 20th century, the identification of the molecules of inheritance loomed as a major challenge to biologists
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5. The Search for the Genetic Material: Scientific Inquiry
When T. H. Morgan’s group showed that genes are located on chromosomes, the two components of chromosomes—DNA and protein—became candidates for the genetic material
The key factor in determining the genetic material was choosing appropriate experimental organisms
The role of DNA in heredity was first discovered by studying bacteria and the viruses that infect them
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6. Evidence That DNA Can Transform Bacteria
The discovery of the genetic role of DNA began with research by Frederick Griffith in 1928
Griffith worked with two strains of a bacterium, one pathogenic and one harmless
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7. When he mixed heat-killed remains of the pathogenic strain with living cells of the harmless strain, some living cells became pathogenic
He called this phenomenon transformation, now defined as a change in genotype and phenotype due to assimilation of foreign DNA
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8. EXPERIMENT RESULTS Fig. 16-2
Mixture of heat-killed S cells and living R cells
EXPERIMENT
Living S cells (control)
Living R cells (control)
Heat-killed S cells (control)
RESULTS
Figure 16.2 Can a genetic trait be transferred between different bacterial strains?
Mouse dies
Mouse healthy
Mouse healthy
Mouse dies
Living S cells

9. In 1944, Oswald Avery, Maclyn McCarty, and Colin MacLeod announced that the transforming substance was DNA
Their conclusion was based on experimental evidence that only DNA worked in transforming harmless bacteria into pathogenic bacteria
Many biologists remained skeptical, mainly because little was known about DNA
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10. Evidence That Viral DNA Can Program Cells
More evidence for DNA as the genetic material came from studies of viruses that infect bacteria
Such viruses, called bacteriophages (or phages), are widely used in molecular genetics research
Animation: Phage T2 Reproductive Cycle
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11. Phage head Tail sheath Tail fiber DNA 100 nm Bacterial cell Fig. 16-3
Figure 16.3 Viruses infecting a bacterial cell
DNA
100 nm
Bacterial
cell

12. Animation: Hershery-Chase Experiment
In 1952, Alfred Hershey and Martha Chase performed experiments showing that DNA is the genetic material of a phage known as T2
To determine the source of genetic material in the phage, they designed an experiment showing that only one of the two components of T2 (DNA or protein) enters an E. coli cell during infection
They concluded that the injected DNA of the phage provides the genetic information
Animation: Hershery-Chase Experiment
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13. Fig. 16-4-1 EXPERIMENT Radioactive protein Phage Bacterial cell DNA
Batch 1: radioactive sulfur (35S)
DNA
Radioactive DNA
Figure 16.4 Is protein or DNA the genetic material of phage T2?
Batch 2: radioactive phosphorus (32P)

14. Fig. 16-4-2 EXPERIMENT Empty protein shell Radioactive protein Phage
Bacterial cell
Batch 1: radioactive sulfur (35S)
DNA
Phage DNA
Radioactive DNA
Figure 16.4 Is protein or DNA the genetic material of phage T2?
Batch 2: radioactive phosphorus (32P)

15. Fig. 16-4-3 EXPERIMENT Empty protein shell
Radioactivity (phage protein) in liquid
Radioactive protein
Phage
Bacterial cell
Batch 1: radioactive sulfur (35S)
DNA
Phage DNA
Centrifuge
Radioactive DNA
Pellet (bacterial cells and contents)
Figure 16.4 Is protein or DNA the genetic material of phage T2?
Batch 2: radioactive phosphorus (32P)
Centrifuge
Radioactivity (phage DNA) in pellet
Pellet

16. Additional Evidence That DNA Is the Genetic Material
It was known that DNA is a polymer of nucleotides, each consisting of a nitrogenous base, a sugar, and a phosphate group
In 1950, Erwin Chargaff reported that DNA composition varies from one species to the next
This evidence of diversity made DNA a more credible candidate for the genetic material
Animation: DNA and RNA Structure
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17. Chargaff’s rules state that in any species there is an equal number of A and T bases, and an equal number of G and C bases
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18. Sugar–phosphate backbone 5 end Sugar (deoxyribose) 3 end
Fig. 16-5
Sugar–phosphate backbone  end
Nitrogenous bases
Thymine (T)
Adenine (A)
Figure 16.5 The structure of a DNA strand
Cytosine (C)
Phosphate
DNA nucleotide
Sugar (deoxyribose)  end
Guanine (G)

19. Building a Structural Model of DNA: Scientific Inquiry
After most biologists became convinced that DNA was the genetic material, the challenge was to determine how its structure accounts for its role
Maurice Wilkins and Rosalind Franklin were using a technique called X-ray crystallography to study molecular structure
Franklin produced a picture of the DNA molecule using this technique
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20. (b) Franklin’s X-ray diffraction photograph of DNA
Fig. 16-6
Figure 16.6 Rosalind Franklin and her X-ray diffraction photo of DNA
(a) Rosalind Franklin
(b) Franklin’s X-ray diffraction photograph of DNA

21. (a) Rosalind Franklin Fig. 16-6a
Figure 16.6 Rosalind Franklin and her X-ray diffraction photo of DNA
(a) Rosalind Franklin

22. (b) Franklin’s X-ray diffraction photograph of DNA
Fig. 16-6b
Figure 16.6 Rosalind Franklin and her X-ray diffraction photo of DNA
(b) Franklin’s X-ray diffraction photograph of DNA

23. Animation: DNA Double Helix
Franklin’s X-ray crystallographic images of DNA enabled Watson to deduce that DNA was helical
The X-ray images also enabled Watson to deduce the width of the helix and the spacing of the nitrogenous bases
The width suggested that the DNA molecule was made up of two strands, forming a double helix
Animation: DNA Double Helix
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24. (a) Key features of DNA structure (b) Partial chemical structure
Fig. 16-7
5 end
Hydrogen bond
3 end
1 nm
3.4 nm
Figure 16.7 The double helix
For the Cell Biology Video Stick Model of DNA (Deoxyribonucleic Acid), go to Animation and Video Files.
For the Cell Biology Video Surface Model of DNA (Deoxyribonucleic Acid), go to Animation and Video Files.
3 end
0.34 nm
5 end
(a) Key features of DNA structure
(b) Partial chemical structure
(c) Space-filling model

25. Fig. 16-7a 5 end Hydrogen bond 3 end 1 nm 3.4 nm 3 end 0.34 nm
Figure 16.7 The double helix
3 end
0.34 nm
5 end
(a) Key features of DNA structure
(b) Partial chemical structure

26. (c) Space-filling model
Fig. 16-7b
Figure 16.7 The double helix
(c) Space-filling model

27. Watson and Crick built models of a double helix to conform to the X-rays and chemistry of DNA
Franklin had concluded that there were two antiparallel sugar-phosphate backbones, with the nitrogenous bases paired in the molecule’s interior
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28. At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width
Instead, pairing a purine with a pyrimidine resulted in a uniform width consistent with the X-ray
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29. Purine + purine: too wide
Fig. 16-UN1
Purine + purine: too wide
Pyrimidine + pyrimidine: too narrow
Purine + pyrimidine: width consistent with X-ray data

30. Watson and Crick reasoned that the pairing was more specific, dictated by the base structures
They determined that adenine (A) paired only with thymine (T), and guanine (G) paired only with cytosine (C)
The Watson-Crick model explains Chargaff’s rules: in any organism the amount of A = T, and the amount of G = C
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31. Fig. 16-8 Adenine (A) Thymine (T) Guanine (G) Cytosine (C)
Figure 16.8 Base pairing in DNA
Guanine (G)
Cytosine (C)

32. Concept 16.2: Many proteins work together in DNA replication and repair
The relationship between structure and function is manifest in the double helix
Watson and Crick noted that the specific base pairing suggested a possible copying mechanism for genetic material
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33. The Basic Principle: Base Pairing to a Template Strand
Since the two strands of DNA are complementary, each strand acts as a template for building a new strand in replication
In DNA replication, the parent molecule unwinds, and two new daughter strands are built based on base-pairing rules
Animation: DNA Replication Overview
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34. Fig. 16-9-1 A T C G T A A T G C (a) Parent molecule
Figure 16.9 A model for DNA replication: the basic concept

35. (b) Separation of strands
Fig A T A T C G C G T A T A A T A T G C G C
(a) Parent molecule
(b) Separation of strands
Figure 16.9 A model for DNA replication: the basic concept

36. (b) Separation of strands
Fig A T A T A T A T C G C G C G C G T A T A T A T A A T A T A T A T G C G C G C G C
(a) Parent molecule
(b) Separation of strands
(c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand
Figure 16.9 A model for DNA replication: the basic concept

37. Watson and Crick’s semiconservative model of replication predicts that when a double helix replicates, each daughter molecule will have one old strand (derived or “conserved” from the parent molecule) and one newly made strand
Competing models were the conservative model (the two parent strands rejoin) and the dispersive model (each strand is a mix of old and new)
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38. (a) Conservative model
Fig
First replication
Second replication
Parent cell
(a) Conservative model
(b) Semiconserva- tive model
Figure Three alternative models of DNA replication
(c) Dispersive model

39. Experiments by Matthew Meselson and Franklin Stahl supported the semiconservative model
They labeled the nucleotides of the old strands with a heavy isotope of nitrogen, while any new nucleotides were labeled with a lighter isotope
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40. The first replication produced a band of hybrid DNA, eliminating the conservative model
A second replication produced both light and hybrid DNA, eliminating the dispersive model and supporting the semiconservative model
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41. Bacteria transferred to medium containing 14N
Fig
EXPERIMENT 1 2
Bacteria transferred to medium containing 14N
Bacteria cultured in medium containing 15N
RESULTS 3 4
Less dense
DNA sample centrifuged after 20 min (after first application)
More dense
DNA sample centrifuged after 40 min (after second replication)
CONCLUSION
First replication
Second replication
Conservative model
Figure Does DNA replication follow the conservative, semiconservative, or dispersive model?
Semiconservative model
Dispersive model

42. Bacteria cultured in medium containing 15N 2
Fig a
EXPERIMENT 1
Bacteria cultured in medium containing 15N 2
Bacteria transferred to medium containing 14N
RESULTS 3
DNA sample centrifuged after 20 min (after first application) 4
DNA sample centrifuged after 20 min (after second replication)
Less dense
Figure Does DNA replication follow the conservative, semiconservative, or dispersive model?
More dense

43. Semiconservative model
Fig b
CONCLUSION
First replication
Second replication
Conservative model
Semiconservative model
Figure Does DNA replication follow the conservative, semiconservative, or dispersive model?
Dispersive model