CHAPTER 10 The Structure and Function of DNA 1. Hereditary information is stored in the chemical language of DNA. 2. DNA directs the biochemical, cellular, anatomical, and physiological activities of the human body. 3. Scientists can manipulate the DNA of cells to modify the traits of crops, transform the characteristics of cells, and treat and potentially prevent disease. 4. Viruses play a key role in the history of molecular biology and continue to be important pathogens in humans, bacteria, plants, and animals. 5. Treatments and cures for viral infections are likely to be the products of research into molecular biology. Biology and Society: Tracking a Killer 1. Explain how flu vaccines are produced and why flu vaccines are important. DNA: Structure and Replication 2. Explain what was and was not known about DNA by the early 1950s. 3. Describe and compare the chemical compositions of DNA and RNA. 4. Describe the key features of the overall shape of a DNA molecule. Explain how Watson and Crick determined the structure of DNA. 5. Describe the process of DNA replication. The Flow of Genetic Information from DNA to RNA to Protein 6. Define transcription and translation. Explain why the hypothesis “one gene-one enzyme” is not correct. 7. Explain how the language of DNA directs the production of polypeptides. 8. Explain how codons are used to construct polypeptides. Explain what the authors mean when they state “there is redundancy in the code but no ambiguity.” 9. Describe the steps of transcription and the processing of RNA before it leaves the nucleus. 10. Compare the structures and functions of mRNA, tRNA, and rRNA. 11. Describe in detail the process of translation. 12. Distinguish between insertion, deletion, and substitution mutations. Explain how mutations can be harmful or beneficial to organisms. Viruses and Other Noncellular Infectious Agents 13. Compare the lytic and lysogenic cycles of bacteriophages. 14. Compare the life cycles of RNA and DNA viruses. Describe the spread, symptoms, and prevention of viral diseases in plants and animals. 15. Describe the reproductive cycle of retroviruses such as HIV and the mechanisms by which AZT and protease inhibitors limit AIDS. 16. Explain how viroids and prions cause disease. Evolution Connection: Emerging Viruses 17. Describe the three processes that contribute to the emergence of viral disease. Key Terms adenine (A) AIDS bacteriophages cap codon cytosine (C) DNA DNA polymerase double helix emerging viruses exons genetic code guanine (G) HIV introns lysogenic cycle lytic cycle messenger RNA molecular biology mutagen mutation nucleotide phages polynucleotide prion promoter prophage provirus retrovirus reverse transcriptase ribosomal RNA (rRNA) RNA polymerase RNA splicing start codon stop codon sugar-phosphate backbone tail terminator thymine (T) transcription transfer RNA (tRNA) translation uracil (U) virus Word Roots muta = change; gen = producing (mutagen: a physical or chemical agent that causes mutations) phage = eat (bacteriophages: viruses that attack bacteria) poly = many (polynucleotide: a polymer of many nucleotides) pro = before (prophage: phage DNA inserted into the bacterial chromosome before viral replication) retro = backward (retrovirus: an RNA virus that reproduces by first transcribing its RNA into DNA then inserting the DNA molecule into a host’s DNA) trans = across; script = write (transcription: the transfer of genetic information from DNA into an RNA molecule) Student Media Activities The Hershey-Chase Experiment DNA and RNA Structure DNA Double Helix DNA Replication: An Overview Overview of Protein Synthesis Transcription RNA Processing Translation Simplified Viral Reproductive Cycle Phage Lytic Cycle Phage Lysogenic and Lytic Cycles Retrovirus (HIV) Reproductive Cycle BioFlix DNA Replication Protein Synthesis Biology Labs On-Line TranslationLab BLAST Animations Hydrogen Bonds in DNA Structure of DNA Double Helix Transcription Translation Roles of RNA HIV Structure AIDS Treatment Strategies MP3 Tutors DNA to RNA to Protein Process of Science What Is the Correct Model for DNA Replication? How Is a Metabolic Pathway Analyzed? How Do You Diagnose a Genetic Disorder? What Causes Infections in AIDS Patients? Why Do AIDS Rates Differ Across the U.S.? Videos Discovery Channel Video: Vaccines Discovery Channel Video: Emerging Diseases Relevant Current Issues in Biology Articles Current Issues in Biology, volume 2 (ISBN 0-8053-7108-7) Detecting Mad Cow Disease Tumor-Busting Viruses Current Issues in Biology, volume 3 (ISBN 0-8053-7527-9) Are Viruses Alive? Current Issues in Biology, volume 4 (ISBN 0-8053-3566-8) Preparing for a Pandemic Founder Mutations Current Issues in Biology, volume 5 (ISBN 0-321-54187-1) Cancer Clues from Pet Dogs Current Issues in Biology, volume 6 (ISBN 0-321-59849-0) Diet Advice From DNA Traces of a Distant Past Relevant Songs to Play in Class “The Jean Genie,” David Bowie “Billy Jean,” Michael Jackson “In Those Jeans,” Ginuwine “Cat DNA,” Ozric Tentacles Chapter Guide to Teaching Resources DNA: Structure and Replication Student Misconceptions and Concerns 1. If your class has not yet studied Chapter 3, consider assigning the Chapter 3 section on “Nucleic Acids” before addressing the contents of Chapter 10. 2. The text describes but does not specifically point out that DNA replication is semiconservative. Tell your students about an experiment in which a DNA molecule is labeled, then replicated. How will the two DNA molecules compare with regard to the location/distribution of the original DNA molecule? Will one DNA molecule be the original and the other the new copy? Or is there another possibility? Half of each of the two DNA molecules is new and half is the original, thus it used semiconservative replication. Analogies for semiconservative replication can be a challenge. But in a sense, DNA replication is similar to parents getting divorced and then each parent remarrying someone else. The two new couples represent “half old parent and half new person.” 3. Students often confuse the terms nucleic acids, nucleotides, and bases. It helps just to note the hierarchy of relationships: nucleic acids consist of long chains of nucleotides, and nucleotides include bases as part of their structure. Teaching Tips 1. Consider comparing DNA, RNA, and proteins to a train (polymer). DNA and RNA are like a train of various lengths and combinations of four types of train cars (monomers). Proteins are also “trains” of various lengths but made of a combination of 20 types of train cars. 2. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. You might remind your class of all the prior research (identifying DNA as the genetic material and clues to its structure) that brought Watson and Crick to their historic conclusions. 3. The authors note that the structure of DNA is analogous to a twisted rope ladder. In class, challenge your students to explain what the parts of the ladder represent. The wooden rungs represent a base pair and each rope the sugar-phosphate backbone. 4. Demonstrate the complementary base pairing within DNA. Present students with the base sequence to one side of a DNA molecule and have them work quickly at their seats to determine the sequence of the complementary strand. For some students, these sorts of quick practice are necessary to reinforce a concept and break up a lecture. 5. To explain the adaptive advantage of multiple replication sites over a single site of replication, ask your students to imagine copying, by hand, the first ten chapters of your biology textbook. The task would certainly go faster if ten students each copied a different chapter! 6. There are about 2 million characters (letters or numbers) in the Campbell Essential Biology with Physiology textbook. The accuracy of DNA replication would be like copying every letter and number in this textbook by hand 500 times and writing just one letter or number incorrectly, making one error in every 1 billion characters! The Flow of Genetic Information from DNA to RNA to Protein Student Misconceptions and Concerns 1. Less experienced students are often intensely focused on writing detailed notes. The risk is that they miss the overall patterns and the broader significance of the topics discussed. Consider a gradual approach to the subjects of transcription and translation, beginning quite generally and testing comprehension, before venturing into the finer mechanics of each process. 2. Consider placing on the board the basic content from Figure 10.9, noting the sequence, products, and locations of transcription and translation in eukaryotic cells. This reminder can create a quick concept check for students as they learn additional detail. 3. Mutations are often discussed as part of evolution mechanisms. In this sense, mutations may be considered a part of a positive creative process. The dual nature of mutations, potentially deadly yet potentially innovative, should be clarified. Teaching Tips 1. It has been said that, “Everything about an organism is an interaction between the genome and the environment.” You might wish to challenge your students to explain the significance and validity of this statement. 2. The authors note that the sequential information in DNA and RNA is analogous to the sequential information in the letters of a sentence. This analogy is also helpful when explaining the impact of insertion or deletion mutations that cause a shift in the reading frame. 3. The transcription of DNA into RNA is like a reporter who transcribes a political speech. In both situations, the language remains the same, although in the case of the reporter, it changes its form from spoken to written. 4. A parallel can be drawn between the discovery in 1799 of the Rosetta stone, which provided the key that enabled scholars to crack the previously indecipherable hieroglyphic code, and the cracking of the genetic code in 1961. Consider challenging your students to explain what part of the genetic code is similar to the Rosetta stone. This could be a short in-class activity for small groups. 5. Another advantage to the use of RNA to direct protein synthesis is that the original code (DNA) remains safely within the nucleus, away from the many potentially damaging chemicals in the cytoplasm. This is like making photocopies of important documents for study, keeping the originals safely stored away. 6. The production of proteins is like a machine requiring fuel. The molecular machinery (ribosomes and tRNA) used in many cellular processes also requires an input of energy in the form of ATP. 7. If you were using a train analogy for the assembly of monomers into polymers, at this point the DNA and RNA “trains” are traded in 3 for 1 for the polypeptide “train.” Thus, in general, polypeptides have about 1/3 as many monomers as the mRNA that coded for them. 8. After translation is addressed, consider asking your students (working singly or in small groups) to list all of the places where base pairing is used (in the construction of a DNA molecule during DNA replication, in transcription, and during translation when the tRNA attaches). 9. Students might want to think of the A and P sites as stages in an assembly line. The A site is where a new amino acid is brought in, according to the blueprint of the codon on the mRNA. The P site is where the growing product/polypeptide is anchored as it is being built. To help them better remember details of translation, students might think of the letters for the two sites to mean “A” for addition, where an amino acid is added, and “P” for polypeptide, where the growing polypeptide is located. 10. A simple way to demonstrate the effect of a reading frame shift is to have students compare the following three sentences. The first is a simple sentence. But look what happens when a letter is added (2) or deleted (3). The “reading frame,” or triplet groupings, are re-formed into nonsense. (1) The big red pig ate the red rag. (2) The big res dpi gat eth ere dra g. (3) The big rep iga tet her edr ag. 11. The authors have noted elsewhere that “A random mutation is like a shot in the dark. It is not likely to improve a genome any more than shooting a bullet through the hood of a car is likely to improve engine performance!” Viruses and Other Noncellular Infectious Agents Student Misconceptions and Concerns 1. Students and many parents with young children expect a treatment of antibiotics for many respiratory infections, even though such infections may result from a virus. Students will benefit by a thorough explanation of the inappropriate use of antibiotics for viral infections and the risks of overuse of antibiotics leading to increased numbers of antibioticresistant bacteria. 2. The success of modern medicine has perhaps led to an overconfidence in our ability to treat disease. Students often do not understand that there are few successful treatments for viral infections. Instead, the best defense against viruses is prevention by reducing the chances of contacting the virus and the use of vaccines. Teaching Tips 1. Students (and instructors) might enjoy thinking of a prophage as a smudge mark on the master copy of a class handout. The smudge is replicated every time the original is copied! 2. Viruses can spread throughout a plant by moving through plasmodesmata (not specifically discussed in this chapter). This is like smoke spreading throughout a building by moving through air ducts. 3. There is an interesting relationship between the speed at which a virus kills or debilitates a host and the extent to which it spreads from one organism to another. This is something to consider for a class discussion. Compare two viral infections. Infection A multiplies within the host, is spread by the host to other people through casual contact, but does not cause its lethal symptoms until 5–10 years after infection. Virus B kills the host within 1–2 days of infection, is easily transmitted, and causes severe symptoms within hours of contact. Which virus is likely to spread the fastest through the human population on Earth? Which might be considered the most dangerous to humans? 4. Students often do not understand the disproportionate distribution of HIV infections and AIDS in our world. Consider an Internet assignment, asking students to identify the regions of the world most affected by HIV-AIDS. The Centers for Disease Control and Prevention has extensive information about AIDS at www.cdc.gov/hiv/. Answers to End-of-Chapter Questions The Process of Science 12. Suggested answer: In this case, two of the daughter cells will have a double helix in which both strands are radioactive. The other two daughter cells will have a double helix in which one strand is radioactive and the other is nonradioactive. 13. Suggested answer: In this experiment one would expect to find the proteins (tagged with radioactive sulfur) outside of the bacterial cells, whereas the viral DNA (tagged with radioactive phosphorous) would be found inside the bacterial cells. This experiment indicates that the viral DNA is the infectious particle as it was the only thing to enter the bacterial cells. Biology and Society 14. Some issues and questions to consider: Is it fair to issue a patent for a gene or gene product that occurs naturally in every human being? Or, should a patent be issued only for something new that is invented rather than found? Suppose another scientist slightly modifies the gene or protein. How different does the gene or protein have to be so that the patent is not infringed? Might patents encourage secrecy and interfere with the free flow of scientific information? What are the benefits to the holder of a patent? When research discoveries cannot be patented, what are the scientists’ incentives for doing the research? What are the incentives for the institution or company that is providing financial support? 15. Tanning by exposure to ultraviolet light causes mutations in skin cells exposed to the light. These mutations increase the risks of developing skin cancer. Additional Critical Thinking Questions The Process of Science 1. What would be the effect of the following mutations on the production of the protein for which a gene codes? a. a mutation in the promoter of a gene, so that RNA polymerase cannot bind to it b. a mutation in an intron of a gene c. a mutation of codon CGA to codon AGA in an exon d. a mutation of a stop codon to one coding for an amino acid Suggested answers: a. A mutation in the promoter, preventing RNA polymerase binding, would mean that the gene is never transcribed, and the protein is never made. b. Since an intron is cut out of mRNA before it is translated, a mutation in an intron of a gene would have no effect on the protein or its production. c. Both of these codons correspond to the amino acid arginine, so there would be no effect on the protein or its production. d. The translation of the protein would not terminate properly but would continue until a stop codon is reached. This would likely produce a protein with an altered function or no function. 2. The base sequence of the gene coding for a short polypeptide is T A C G C T A G G C G A T T G A C T. What would be the base sequence of the mRNA transcribed from this gene? Using the genetic code in Figure 10.10, state the amino acid sequence of the polypeptide translated from this mRNA. Suggested answer: mRNA: AUGCGAUCCGCUAACUGA. Amino acids: Met-ArgSer-Ala-Asn. 3. In the early 1950s, scientists considered several different hypotheses about how DNA is replicated. One hypothesis, called conservative replication, was that the doublestranded parental DNA molecule is conserved intact but somehow directs the synthesis of a daughter DNA molecule consisting of two entirely new strands. Another hypothesis, semiconservative replication, was that the two strands of the parental DNA separate and each acts as a template for the construction of a new strand, yielding two daughter molecules, that each have one old and one new strand. This hypothesis turned out to be correct. Assume you grow bacteria in a medium containing radioactive phosphorus, so all their DNA is labeled, and then you transfer them to a medium containing only nonradioactive phosphorus. After precisely one cell division in the nonradioactive medium, you test the bacterial DNA for radioactivity. a. The results that would support the conservative replication hypothesis would be that: b. The results that would support the semiconservative replication hypothesis would be that: (For the two questions above, select one of the answers below, state why you chose it, and state why you rejected each of the other choices.) a. none of the DNA would be radioactive; all the DNA would be radioactive b. all the DNA would be radioactive; half the DNA would be radioactive c. half the DNA would be radioactive; all the DNA would be radioactive d. None of these. This experiment would not be able to distinguish between the two hypotheses. Suggested answers: a. No. The conservative replication theory would predict that after one cell division, the DNA of half the cells would be entirely radioactive, and the DNA of the other half of the cells would be all new and completely nonradioactive. b. No. This is the reverse of the correct answer; see answer c. c. Correct. The conservative replication hypothesis predicts that after one cell division, half the cells will contain entirely new, nonradioactive DNA, and half the cells will contain entirely old, radioactive DNA. The semiconservative replication hypothesis predicts that each cell will have DNA consisting of one old strand (radioactive) and one new strand (nonradioactive) and therefore that all the DNA molecules in all the cells will contain some radioactivity. d. No. This experiment could distinguish very well between the hypotheses. Biology and Society 4. Our civilization generates many potentially mutagenic chemicals (pesticides, for example) and modifies the environment in ways that increase exposure to other mutagens, notably ultraviolet (UV) radiation. What role should government play in identifying mutagens and regulating their release to the environment? Some issues and questions to consider: Does the government have an obligation to protect the health of its citizens? Can too much government regulation stifle the economy? What is the proper balance between protection from harm and government regulation? Is it possible to identify and monitor every possible mutagen? Should we try? 5. There are many environmental mutagens whose effects have been clearly noted in humans. Some examples include the chemicals in cigarette smoke and UV exposure. Knowing that the risks of exposure carry such high odds of a dangerous outcome such as cancer, many people still voluntarily expose themselves to these mutagens. Should people be responsible for regulating their own activities, or should there be more legislation to prevent this? If people choose to smoke and then develop lung cancer or choose to overexpose themselves to the sun and develop malignant melanoma, should they be held accountable for their actions? If so, should they foot the bill for health care? Should their insurance cover the expense? Should these people be able to sue others for financial gain when they were fully aware of the dangers associated with the exposure? Some issues and questions to consider: How responsible is a person for his or her own actions? If the dangers are clearly indicated and the person makes their own choice, should they suffer the consequences? Should insurance companies be responsible for paying for claims that were derived in this manner? Should they be allowed to deny coverage for these people? If so, where do they draw the line? Are you willing to pay higher insurance premiums to cover these costs? Should the government do more to deter people from habits such as smoking?