1. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings PowerPoint Lectures for Biology, Seventh Edition Neil Campbell and Jane Reece Lectures by Chris Romero DNA: The Molecular Basis of Inheritance

2. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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

3. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA, the substance of inheritance – Is the most celebrated molecule of our time Hereditary information – Is encoded in the chemical language of DNA and reproduced in all the cells of your body

4. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings The Search for the Genetic Material: Scientific Inquiry The role of DNA in heredity – Was first worked out by studying bacteria and the viruses that infect them

5. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Evidence That DNA Can Transform Bacteria 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 Pathogenic- capable of causing disease Nonpathogenic- incapable of causing disease

6. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Results from Griffith’s experiments. 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 diesMouse healthy Mouse dies Living S cells are found in blood sample.

7. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Tranformation Griffith called the phenomenon transformation – Now defined as a change in genotype and phenotype due to the assimilation or integration of external DNA by a cell

8. 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

9. 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 100 nm

10. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Additional Evidence That DNA Is the Genetic Material 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– O P O CH 2 5 4 O–O– H H O H H H 3 1 H O CH 3 N O N H Thymine (T) O OP O O–O– CH 2 H H O H H H H N N N H N H H Adenine (A) O O P O O–O– CH 2 H H O H H H H H H H N N N O Cytosine (C) O O P O CH 2 5 4 O–O– H O H H 3 1 OH 2 H N N N H O N N H H H H Sugar (deoxyribose) 3 end Phosphate Guanine (G) DNA nucleotide 2 N Figure 16.5

11. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Watson and Crick deduced that DNA was a double helix Figure 16.7a, c C T A A T C G GC A C G A T A T AT T A C T A 0.34 nm 3.4 nm (a) Key features of DNA structure G 1 nm G (c) Space-filling model T – Through observations of the X-ray crystallographic images of DNA

13. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA double- helical structure DNA – 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 – A goes with T, and C goes with G

14. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Hydrogen Bonding between bases: O –O–O O OH O –O–O O O H2CH2C O –O–O O O H2CH2C O –O–O O O O O O T A C G C A T O O O CH 2 O O–O– O O 5 end Hydrogen bond 3 end G P P P P O OH O–O– O O O P P O–O– O O O P O–O– O O O P (b) Partial chemical structure H2CH2C 5 end Figure 16.7b O

15. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Purine- A & GPyramidine- C & T N H O CH 3 N N O N N N NH Sugar Adenine (A) Thymine (T) N N N N Sugar O H N H N H N O H H N Guanine (G) Cytosine (C) Figure 16.8 H

16. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings 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

17. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings In DNA replication – The parent molecule unwinds, each strand is now a template, 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

18. 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

19. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Getting Started: Origins of Replication The replication of a DNA molecule – Begins at special sites called origins of replication, where the two strands are separated

20. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 16.13 New strandTemplate 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 A T C G G C A C T 3 end Pyrophosphate 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 from the 5’ to 3’ direction on the new strand. Nucleoside triphosphate

21. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings DNA polymerases add nucleotides to complete strands DNA Polymerase can synthesize a complementary strand continuously, moving toward the replication fork

22. 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

23. 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

24. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Telomeres: http://learn.genetics.utah.edu/content/begin/traits/telomeres/

25. 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