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Molecular Biology of the Gene
Chapter 10 Molecular Biology of the Gene
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The Structure of the Genetic Material DNA Replication
Figure 10.0_1 Chapter 10: Big Ideas The Structure of the Genetic Material DNA Replication Figure 10.0_1 Chapter 10: Big Ideas The Flow of Genetic Information from DNA to RNA to Protein The Genetics of Viruses and Bacteria 2
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10.1 SCIENTIFIC DISCOVERY: Experiments showed that DNA is the genetic material
Until the 1940s, the case for proteins serving as the genetic material was stronger than the case for DNA. Proteins are made from 20 different amino acids. DNA was known to be made from just four kinds of nucleotides. Studies of bacteria and viruses ushered in the field of molecular biology, the study of heredity at the molecular level, and revealed the role of DNA in heredity. Student Misconceptions and Concerns 1. Understanding bacteriophage replication can be difficult for students with limited knowledge of cell biology or genetics. Therefore, understanding the methods, results, and significance of the Hershey and Chase experiments is even more problematic. Considerable time and attention to these details will be required for many of your students. 2. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. Teaching Tips 1. A phage functions like a needle and syringe, injecting a drug. The needle and syringe are analogous to the protein components of the phage. The drug to be injected is analogous to the phage DNA. 2. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). © 2012 Pearson Education, Inc. 3
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10.1 SCIENTIFIC DISCOVERY: Experiments showed that DNA is the genetic material
In 1928, Frederick Griffith discovered that a “transforming factor” could be transferred into a bacterial cell. He found that when he exposed heat-killed pathogenic bacteria to harmless bacteria, some harmless bacteria were converted to disease-causing bacteria and the disease-causing characteristic was inherited by descendants of the transformed cells. Student Misconceptions and Concerns 1. Understanding bacteriophage replication can be difficult for students with limited knowledge of cell biology or genetics. Therefore, understanding the methods, results, and significance of the Hershey and Chase experiments is even more problematic. Considerable time and attention to these details will be required for many of your students. 2. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. Teaching Tips 1. A phage functions like a needle and syringe, injecting a drug. The needle and syringe are analogous to the protein components of the phage. The drug to be injected is analogous to the phage DNA. 2. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). © 2012 Pearson Education, Inc. 4
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Griffith’s experiment
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10.1 SCIENTIFIC DISCOVERY: Experiments showed that DNA is the genetic material
In 1952, Alfred Hershey and Martha Chase used bacteriophages to show that DNA is the genetic material of T2, a virus that infects the bacterium Escherichia coli (E. coli). Bacteriophages (or phages for short) are viruses that infect bacterial cells. Phages were labeled with radioactive sulfur to detect proteins or radioactive phosphorus to detect DNA. Bacteria were infected with either type of labeled phage to determine which substance was injected into cells and which remained outside the infected cell. Student Misconceptions and Concerns 1. Understanding bacteriophage replication can be difficult for students with limited knowledge of cell biology or genetics. Therefore, understanding the methods, results, and significance of the Hershey and Chase experiments is even more problematic. Considerable time and attention to these details will be required for many of your students. 2. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. Teaching Tips 1. A phage functions like a needle and syringe, injecting a drug. The needle and syringe are analogous to the protein components of the phage. The drug to be injected is analogous to the phage DNA. 2. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). © 2012 Pearson Education, Inc. 6
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Animation: Hershey-Chase Experiment
10.1 SCIENTIFIC DISCOVERY: Experiments showed that DNA is the genetic material The sulfur-labeled protein stayed with the phages outside the bacterial cell, while the phosphorus-labeled DNA was detected inside cells. Cells with phosphorus-labeled DNA produced new bacteriophages with radioactivity in DNA but not in protein. Student Misconceptions and Concerns 1. Understanding bacteriophage replication can be difficult for students with limited knowledge of cell biology or genetics. Therefore, understanding the methods, results, and significance of the Hershey and Chase experiments is even more problematic. Considerable time and attention to these details will be required for many of your students. 2. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. Teaching Tips 1. A phage functions like a needle and syringe, injecting a drug. The needle and syringe are analogous to the protein components of the phage. The drug to be injected is analogous to the phage DNA. 2. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). Animation: Hershey-Chase Experiment © 2012 Pearson Education, Inc. 7
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Figure 10.1A Head DNA Tail Tail fiber Figure 10.1A Phage T2 8
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The radioactivity is in the liquid.
Figure 10.1B Radioactive protein Empty protein shell Phage The radioactivity is in the liquid. Bacterium Phage DNA Batch 1: Radioactive protein labeled in yellow DNA Centrifuge Pellet 1 2 3 4 Figure 10.1B The Hershey-Chase experiment Batch 2: Radioactive DNA labeled in green Radioactive DNA Centrifuge The radioactivity is in the pellet. Pellet 9
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10.2 DNA and RNA are polymers of nucleotides
DNA and RNA are nucleic acids. One of the two strands of DNA is a DNA polynucleotide, a nucleotide polymer (chain). A nucleotide is composed of a nitrogenous base, five-carbon sugar, and phosphate group. The nucleotides are joined to one another by a sugar-phosphate backbone. Student Misconceptions and Concerns 1. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. 2. Students often confuse the terms nucleic acids, nucleotides, and bases. It helps to note the hierarchy of relationships: nucleic acids consist of long chains of nucleotides (polynucleotides), while nucleotides include nitrogenous bases. Teaching Tips 1. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). 2. 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. © 2012 Pearson Education, Inc. 10
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10.2 DNA and RNA are polymers of nucleotides
Each type of DNA nucleotide has a different nitrogen-containing base: adenine (A), cytosine (C), thymine (T), and guanine (G). Student Misconceptions and Concerns 1. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. 2. Students often confuse the terms nucleic acids, nucleotides, and bases. It helps to note the hierarchy of relationships: nucleic acids consist of long chains of nucleotides (polynucleotides), while nucleotides include nitrogenous bases. Teaching Tips 1. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). 2. 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. © 2012 Pearson Education, Inc. 11
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10.2 DNA and RNA are Polymers of Nucleotides
RNA (ribonucleic acid) is unlike DNA in that it uses the sugar ribose (instead of deoxyribose in DNA) and RNA has the nitrogenous base uracil (U) instead of thymine. Student Misconceptions and Concerns 1. If your class has not yet studied Chapter 3, consider assigning module 3.15 on “Nucleic Acids” before addressing the contents of Chapter 10. 2. Students often confuse the terms nucleic acids, nucleotides, and bases. It helps to note the hierarchy of relationships: nucleic acids consist of long chains of nucleotides (polynucleotides), while nucleotides include nitrogenous bases. Teaching Tips 1. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). 2. 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. © 2012 Pearson Education, Inc. 12
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10.3 SCIENTIFIC DISCOVERY: DNA is a double-stranded helix
Watson and Crick reported that DNA consisted of two polynucleotide strands wrapped into a double helix. The sugar-phosphate backbone is on the outside. The nitrogenous bases are in the interior. Specific pairs of bases give the helix a uniform shape. A pairs with T, forming two hydrogen bonds, and G pairs with C, forming three hydrogen bonds. Student Misconceptions and Concerns Students often confuse the terms nucleic acids, nucleotides, and bases. It helps to note the hierarchy of relationships: nucleic acids consist of long chains of nucleotides (polynucleotides), while nucleotides include nitrogenous bases. Teaching Tips 1. The descriptions of the discovery of DNA’s structure are a good time to point out that science is a collaborative effort. Watson, Crick, and Wilkins earned Nobel prizes due to their historic conclusions based upon the work of many others (including Franklin, Griffith, Hershey, Chase, and Chargaff). 2. 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 pairs of nitrogenous bases joined by hydrogen bonds. Each rope represents a sugar-phosphate backbone. © 2012 Pearson Education, Inc. 13
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Partial chemical structure
Figure 10.3D Hydrogen bond Base pair Figure 10.3D Three representations of DNA Ribbon model Partial chemical structure Computer model 14
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10.4 DNA replication depends on specific base pairing
DNA replication follows a semiconservative model. The two DNA strands separate. Each strand is used as a pattern to produce a complementary strand, using specific base pairing. Each new DNA helix has one old strand with one new strand. DNA replication ensures that all the somatic cells in a multicellular organism carry the same genetic information. Student Misconceptions and Concerns The authors note that although the general process of semiconservative DNA replication is relatively simple, it involves complex biochemical gymnastics. The DNA molecule is unwound, each strand is copied simultaneously, the correct bases are inserted, and the product is proofread and corrected. Before discussing these details, be sure that your students understand the overall process, what is accomplished, and why each step is important. Teaching Tips 1. 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 complimentary strand. For some students, these sorts of quick practice are necessary to reinforce a concept and break up a lecture. 2. The semiconservative model of DNA replication is like making a photo from a negative and then a new negative from the photo. In each new negative and photo pair, the new item was made from an old item. Animation: DNA Replication Overview © 2012 Pearson Education, Inc. 15
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A parental molecule of DNA
Figure 10.4A_s3 A T T A A T A T A T C G C G G C G C G C G C G C C G C G C A A T A T A T A T Free nucleotides T A T A T A T A A parental molecule of DNA The parental strands separate and serve as templates Two identical daughter molecules of DNA are formed Figure 10.4A-s3 A template model for DNA replication (step 3) 16
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Daughter DNA molecules
Figure 10.4B A T G C A T Parental DNA molecule A T T A C G C G T Daughter strand A C G C G C G Parental strand T C G A Figure 10.4B The untwisting and replication of DNA C G A T T A A T C G G C A T T A T A A T G C Daughter DNA molecules 17
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10.5 DNA replication proceeds in two directions at many sites simultaneously
DNA replication begins at the origins of replication where DNA unwinds at the origin to produce a “bubble,” replication proceeds in both directions from the origin, and replication ends when products from the bubbles merge with each other. Student Misconceptions and Concerns The authors note that although the general process of semiconservative DNA replication is relatively simple, it involves complex biochemical gymnastics. The DNA molecule is unwound, each strand is copied simultaneously, the correct bases are inserted, and the product is proofread and corrected. Before discussing these details, be sure that your students understand the overall process, what is accomplished, and why each step is important. Teaching Tips 1. To explain the adaptive advantage of multiple replication sites over a single site of replication, ask the 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. 2. There are about 500,000 words in the Biology: Concepts & Connections textbook. The accuracy of DNA replication would be like copying every word in this textbook by hand 2,000 times and writing just one word incorrectly, making one error in every 1 billion words. © 2012 Pearson Education, Inc. 18
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Two daughter DNA molecules
Figure 10.5A Parental DNA molecule Origin of replication Parental strand Daughter strand “Bubble” Figure 10.5A Multiple bubbles in replicating DNA Two daughter DNA molecules 19
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10.5 DNA replication proceeds in two directions at many sites simultaneously
DNA replication occurs in the 5 to 3 direction. Replication is continuous on the 3 to 5 template. Replication is discontinuous on the 5 to 3 template, forming short segments. Student Misconceptions and Concerns The authors note that although the general process of semiconservative DNA replication is relatively simple, it involves complex biochemical gymnastics. The DNA molecule is unwound, each strand is copied simultaneously, the correct bases are inserted, and the product is proofread and corrected. Before discussing these details, be sure that your students understand the overall process, what is accomplished, and why each step is important. Teaching Tips 1. To explain the adaptive advantage of multiple replication sites over a single site of replication, ask the 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. 2. There are about 500,000 words in the Biology: Concepts & Connections textbook. The accuracy of DNA replication would be like copying every word in this textbook by hand 2,000 times and writing just one word incorrectly, making one error in every 1 billion words. © 2012 Pearson Education, Inc. 20
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10.5 DNA replication proceeds in two directions at many sites simultaneously
Two key proteins are involved in DNA replication. DNA ligase joins small fragments into a continuous chain. DNA polymerase adds nucleotides to a growing chain and proofreads and corrects improper base pairings. Animation: Origins of Replication Student Misconceptions and Concerns The authors note that although the general process of semiconservative DNA replication is relatively simple, it involves complex biochemical gymnastics. The DNA molecule is unwound, each strand is copied simultaneously, the correct bases are inserted, and the product is proofread and corrected. Before discussing these details, be sure that your students understand the overall process, what is accomplished, and why each step is important. Teaching Tips 1. To explain the adaptive advantage of multiple replication sites over a single site of replication, ask the 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. 2. There are about 500,000 words in the Biology: Concepts & Connections textbook. The accuracy of DNA replication would be like copying every word in this textbook by hand 2,000 times and writing just one word incorrectly, making one error in every 1 billion words. Animation: Leading Strand Animation: Lagging Strand Animation: DNA Replication Review © 2012 Pearson Education, Inc. 21
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DNA polymerase molecule
Figure 10.5C 3 DNA polymerase molecule This daughter strand is synthesized continuously 5 Parental DNA 5 3 Replication fork This daughter strand is synthesized in pieces 3 5 Figure 10.5C How daughter DNA strands are synthesized 5 3 DNA ligase Overall direction of replication 22
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10.6 The DNA genotype is expressed as proteins, which provide the molecular basis for phenotypic traits DNA specifies traits by dictating protein synthesis. The molecular chain of command is from DNA in the nucleus to RNA and RNA in the cytoplasm to protein. Transcription is the synthesis of RNA under the direction of DNA. Translation is the synthesis of proteins under the direction of RNA. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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 the basic content from Figure 10.6A on the board, 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. 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 evaluate the validity of this statement. 2. The information in DNA is used to direct the production of RNA, which in turn directs the production of proteins. However, in Chapter 3, four different types of biological molecules were noted as significant components of life. Students who think this through might wonder, and you could point out, that DNA does not directly control the production of carbohydrates and lipids. So how does DNA exert its influence over the synthesis of these two chemical groups? The answer is largely by way of enzymes, proteins with the ability to promote the production of carbohydrates and lipids. © 2012 Pearson Education, Inc. 23
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DNA Transcription RNA NUCLEUS CYTOPLASM Translation Protein
Figure 10.6A_s3 DNA Transcription RNA NUCLEUS CYTOPLASM Translation Figure 10.6A_s3 The flow of genetic information in a eukaryotic cell (step 3) Protein 24
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10.7 Genetic information written in codons is translated into amino acid sequences
The sequence of nucleotides in DNA provides a code for constructing a protein. Protein construction requires a conversion of a nucleotide sequence to an amino acid sequence. Transcription rewrites the DNA code into RNA, using the same nucleotide “language.” Translation involves switching from the nucleotide “language” to the amino acid “language.” Each amino acid is specified by a codon. 64 codons are possible. Some amino acids have more than one possible codon. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. The transcription of DNA into RNA is like a reporter’s transcription of 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 language. 2. 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 (see Module 10.16). © 2012 Pearson Education, Inc. 25
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10.9 Transcription produces genetic messages in the form of RNA
Overview of transcription An RNA molecule is transcribed from a DNA template by a process that resembles the synthesis of a DNA strand during DNA replication. RNA nucleotides are linked by the transcription enzyme RNA polymerase. Specific sequences of nucleotides along the DNA mark where transcription begins and ends. The “start transcribing” signal is a nucleotide sequence called a promoter. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. As students learn about transcription, they might wonder which of the two strands of DNA is read. This uncertainty may add to the confusion about the details of the process, and students might not even think to ask. As noted in Module 10.9, the location of the promoter, a specific binding site for RNA polymerase, determines which strand is read. Teaching Tips 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. © 2012 Pearson Education, Inc. 26
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T A C T T C A A A A T C A T G A A G T T T T A G A U G A A G U U U U A
Figure 10.8B_s3 Strand to be transcribed T A C T T C A A A A T C DNA A T G A A G T T T T A G Transcription RNA A U G A A G U U U U A G Figure 10.8B_s3 Deciphering the genetic information in DNA (step 3) Start codon Stop codon Translation Polypeptide Met Lys Phe 27
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10.9 Transcription produces genetic messages in the form of RNA
Transcription begins with initiation, as the RNA polymerase attaches to the promoter. During the second phase, elongation, the RNA grows longer. As the RNA peels away, the DNA strands rejoin. Finally, in the third phase, termination, the RNA polymerase reaches a sequence of bases in the DNA template called a terminator, which signals the end of the gene. The polymerase molecule now detaches from the RNA molecule and the gene. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. As students learn about transcription, they might wonder which of the two strands of DNA is read. This uncertainty may add to the confusion about the details of the process, and students might not even think to ask. As noted in Module 10.9, the location of the promoter, a specific binding site for RNA polymerase, determines which strand is read. Teaching Tips 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. Animation: Transcription © 2012 Pearson Education, Inc. 28
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Direction of transcription Template strand of DNA
Figure 10.9A Free RNA nucleotides RNA polymerase T C C A A T A U T C T G U G A C C A U C C A C A G T A G G T T A Figure 10.9A A close-up view of transcription Direction of transcription Template strand of DNA Newly made RNA 29
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Terminator DNA RNA polymerase DNA of gene Promoter DNA Initiation
Figure 10.9B RNA polymerase Terminator DNA DNA of gene Promoter DNA 1 Initiation 2 Elongation Area shown in Figure 10.9A Figure 10.9B The transcription of a gene Growing RNA 3 Termination Completed RNA RNA polymerase 30
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10.10 Eukaryotic RNA is processed before leaving the nucleus as mRNA
Messenger RNA (mRNA) conveys genetic messages from DNA to the translation machinery of the cell Eukaryotic mRNA has introns, interrupting sequences that separate exons, the coding regions. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips Many analogies can be developed to represent the selective expression of a gene requiring the deletion of introns. Instructors that only assign some modules of a chapter are treating the chapters like sections of exons and introns, portions to be read and portions to be skipped. Alternately, students who highlight a chapter might be thought of as editing the book into exons, portions to be reviewed, and introns, nonhighlighted sections that will not be studied. Both analogies are imperfect, but may still convey the concept of selective reading. © 2012 Pearson Education, Inc. 31
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10.10 Eukaryotic RNA is processed before leaving the nucleus as mRNA
Eukaryotic mRNA undergoes processing before leaving the nucleus. RNA splicing removes introns and joins exons to produce a continuous coding sequence. A cap and tail of extra nucleotides are added to the ends of the mRNA Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips Many analogies can be developed to represent the selective expression of a gene requiring the deletion of introns. Instructors that only assign some modules of a chapter are treating the chapters like sections of exons and introns, portions to be read and portions to be skipped. Alternately, students who highlight a chapter might be thought of as editing the book into exons, portions to be reviewed, and introns, nonhighlighted sections that will not be studied. Both analogies are imperfect, but may still convey the concept of selective reading. © 2012 Pearson Education, Inc. 32
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Transcription Addition of cap and tail Cap
Figure 10.10 Exon Intron Exon Intron Exon DNA Transcription Addition of cap and tail Cap RNA transcript with cap and tail Introns removed Tail Exons spliced together mRNA Coding sequence Figure The production of eukaryotic mRNA NUCLEUS CYTOPLASM 33
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10.8 The genetic code dictates how codons are translated into amino acids
Characteristics of the genetic code Three nucleotides specify one amino acid. 61 codons correspond to amino acids. AUG codes for methionine and signals the start of transcription. 3 “stop” codons signal the end of translation. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. You may want to note the parallel 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 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. 2. The authors note the universal use of the genetic code in all forms of life. The evolutionary significance of this fundamental, universal language is a reminder of the shared ancestry of all life. The universal genetic code is part of the overwhelming evidence for evolution. © 2012 Pearson Education, Inc. 34
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Second base First base Third base Figure 10.8A
Figure 10.8A Dictionary of the genetic code (RNA codons) 35
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10.11 Transfer RNA molecules serve as interpreters during translation
Transfer RNA (tRNA) converts the genetic message of mRNA into the language of proteins. Transfer RNA molecules pick up the appropriate amino acid using a special triplet of bases, called an anticodon, recognize the appropriate codons in the mRNA. Translation occurs on the surface of the ribosome. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips The unique structure of tRNA, with binding sites for an amino acid and its codon, permits the translation of the genetic code. Like an interpreter who speaks two languages, the tRNA molecules match codons to the specified amino acid. © 2012 Pearson Education, Inc. 36
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tRNA binding sites Large subunit P site A site Small subunit
Figure 10.12B tRNA binding sites Large subunit P site A site Small subunit Figure 10.12B A ribosome with empty binding sites mRNA binding site 37
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The next amino acid to be added to the polypeptide Growing polypeptide
Figure 10.12C The next amino acid to be added to the polypeptide Growing polypeptide mRNA tRNA Codons Figure 10.12C A ribosome with occupied binding sites 38
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10.13 An initiation codon marks the start of an mRNA message
Translation can be divided into the same three phases as transcription: initiation, elongation, and termination. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. Ribosomal RNA is transcribed in the nucleolus of eukaryotic cells. The ribosomal subunits are assembled in the nucleus using proteins imported from the cytosol. These subunits are then exported to the cytosol, where they are only assembled into a functional ribosome when they attach to an mRNA molecule. Some of these details are not specifically noted in the text, but may be required to fill out your explanations. 2. If you use a train analogy for the assembly of monomers into polymers, the DNA and RNA trains are traded in on a three-for-one basis for the polypeptide train during translation. In general, this produces polypeptides that have about one-third as many monomers as the mRNA that coded for them. © 2012 Pearson Education, Inc. 39
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10.13 An initiation codon marks the start of an mRNA message
Initiation establishes where translation will begin. Initiation occurs in two steps. An mRNA molecule binds to a small ribosomal subunit and the first tRNA binds to mRNA at the start codon. The start codon reads AUG and codes for methionine. The first tRNA has the anticodon UAC. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. Ribosomal RNA is transcribed in the nucleolus of eukaryotic cells. The ribosomal subunits are assembled in the nucleus using proteins imported from the cytosol. These subunits are then exported to the cytosol, where they are only assembled into a functional ribosome when they attach to an mRNA molecule. Some of these details are not specifically noted in the text, but may be required to fill out your explanations. 2. If you use a train analogy for the assembly of monomers into polymers, the DNA and RNA trains are traded in on a three-for-one basis for the polypeptide train during translation. In general, this produces polypeptides that have about one-third as many monomers as the mRNA that coded for them. © 2012 Pearson Education, Inc. 40
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Large ribosomal subunit
Figure 10.13B Met Met Initiator tRNA Large ribosomal subunit P site A site mRNA U A C U A C A U G A U G Start codon Figure 10.13B The initiation of translation Small ribosomal subunit 1 2 41
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10.14 Elongation adds amino acids to the polypeptide chain until a stop codon terminates translation
Each cycle of elongation has three steps. Codon recognition: The anticodon of an incoming tRNA molecule, carrying its amino acid, pairs with the mRNA codon in the A site of the ribosome. Peptide bond formation: The new amino acid is joined to the chain. Translocation: tRNA is released from the P site and the ribosome moves tRNA from the A site into the P site. Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. 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 students better remember details of translation, they might think of the letters for the two sites as meaning A for addition, where an amino acid is added, and P for polypeptide, where the growing polypeptide is located. 2. If you use a train analogy for the assembly of monomers into polymers, the DNA and RNA trains are traded in on a three-for-one basis for the polypeptide train during translation. In general, this produces polypeptides that have about one-third as many monomers as the mRNA that coded for them. © 2012 Pearson Education, Inc. 42
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Animation: Translation
10.14 Elongation adds amino acids to the polypeptide chain until a stop codon terminates translation Elongation continues until the termination stage of translation, when the ribosome reaches a stop codon, the completed polypeptide is freed from the last tRNA, Student Misconceptions and Concerns Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Teaching Tips 1. 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 students better remember details of translation, they might think of the letters for the two sites as meaning A for addition, where an amino acid is added, and P for polypeptide, where the growing polypeptide is located. 2. If you use a train analogy for the assembly of monomers into polymers, the DNA and RNA trains are traded in on a three-for-one basis for the polypeptide train during translation. In general, this produces polypeptides that have about one-third as many monomers as the mRNA that coded for them. Animation: Translation © 2012 Pearson Education, Inc. 43
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Polypeptide Amino acid Anticodon mRNA Codons Codon recognition
Figure 10.14_s4 Polypeptide Amino acid P site A site Anticodon mRNA Codons 1 Codon recognition mRNA movement Stop codon Figure 10.14_s4 Polypeptide elongation (step 4) 2 Peptide bond formation New peptide bond 3 Translocation 44
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Figure 10.15 A summary of transcription and translation
DNA mRNA 1 Transcription RNA polymerase Translation CYTOPLASM Amino acid Amino acid 2 attachment Enzyme tRNA ATP Anticodon Initiator tRNA Large ribosomal subunit 3 Initiation of polypeptide synthesis Start Codon Small ribosomal subunit mRNA New peptide bond forming Growing polypeptide Figure A summary of transcription and translation 4 Elongation Codons mRNA Polypeptide 5 Termination Stop codon 45
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10.16 Mutations can change the meaning of genes
A mutation is any change in the nucleotide sequence of DNA. Mutations can involve large chromosomal regions or just a single nucleotide pair. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Mutations are often discussed as part of evolutionary mechanisms. In this sense, mutations may be considered a part of a creative process. The dual nature of mutations, potentially deadly yet potentially innovative, should be clarified. Teaching Tips 1. 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. However, look what happens when a letter is added (2) or deleted (3). The reading frame, or words, 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. 2. The authors have noted elsewhere that “A random mutation is like a random 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!” © 2012 Pearson Education, Inc. 46
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10.16 Mutations can change the meaning of genes
Mutations within a gene can be divided into two general categories. Base substitutions involve the replacement of one nucleotide with another. Base substitutions may have no effect at all, producing a silent mutation, change the amino acid coding, producing a missense mutation, which produces a different amino acid, lead to a base substitution that produces an improved protein that enhances the success of the mutant organism and its descendant, or change an amino acid into a stop codon, producing a nonsense mutation. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Mutations are often discussed as part of evolutionary mechanisms. In this sense, mutations may be considered a part of a creative process. The dual nature of mutations, potentially deadly yet potentially innovative, should be clarified. Teaching Tips 1. 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. However, look what happens when a letter is added (2) or deleted (3). The reading frame, or words, 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. 2. The authors have noted elsewhere that “A random mutation is like a random 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!” © 2012 Pearson Education, Inc. 47
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Sickle-cell hemoglobin
Figure 10.16A Normal hemoglobin DNA Mutant hemoglobin DNA C T T C A T mRNA mRNA G A A G U A Normal hemoglobin Figure 10.16A The molecular basis of sickle-cell disease Sickle-cell hemoglobin Glu Val 48
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10.16 Mutations can change the meaning of genes
Mutations can result in deletions or insertions that may alter the reading frame (triplet grouping) of the mRNA, so that nucleotides are grouped into different codons, lead to significant changes in amino acid sequence downstream of the mutation, and produce a nonfunctional polypeptide. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Mutations are often discussed as part of evolutionary mechanisms. In this sense, mutations may be considered a part of a creative process. The dual nature of mutations, potentially deadly yet potentially innovative, should be clarified. Teaching Tips 1. 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. However, look what happens when a letter is added (2) or deleted (3). The reading frame, or words, 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. 2. The authors have noted elsewhere that “A random mutation is like a random 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!” © 2012 Pearson Education, Inc. 49
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10.16 Mutations can change the meaning of genes
Mutations can be caused by spontaneous errors that occur during DNA replication or recombination or mutagens, which include high-energy radiation such as X-rays and ultraviolet light and chemicals. Student Misconceptions and Concerns 1. Beginning college students are often intensely focused on writing detailed notes. The risk is that they will 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. Mutations are often discussed as part of evolutionary mechanisms. In this sense, mutations may be considered a part of a creative process. The dual nature of mutations, potentially deadly yet potentially innovative, should be clarified. Teaching Tips 1. 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. However, look what happens when a letter is added (2) or deleted (3). The reading frame, or words, 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. 2. The authors have noted elsewhere that “A random mutation is like a random 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!” © 2012 Pearson Education, Inc. 50
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Nucleotide substitution
Figure 10.16B Normal gene A U G A A G U U U G G C G C A mRNA Protein Met Lys Phe Gly Ala Nucleotide substitution A U G A A G U U U A G C G C A Met Lys Phe Ser Ala U Deleted Nucleotide deletion A U G A A G U U G G C G C A U Figure 10.16B Types of mutations and their effects Met Lys Leu Ala His Inserted Nucleotide insertion A U G A A G U U G U G G C G C Met Lys Leu Ala His 51
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Viruses Viruses are not generally considered alive because they
Viruses are not generally considered alive because they are not cellular and cannot reproduce on their own. © 2012 Pearson Education, Inc. 52
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10.17 Viral DNA may become part of the host chromosome
A virus is essentially “genes in a box,” an infectious particle consisting of a bit of nucleic acid, wrapped in a protein coat called a capsid Viruses have two types of reproductive cycles. In the lytic cycle, viral particles are produced using host cell components, the host cell lyses, and viruses are released. Student Misconceptions and Concerns 1. Students and many parents with young children expect antibiotics to be used to treat many respiratory infections, even though such infections may result from a virus. Students will benefit from a thorough explanation of why antibiotics are inappropriate for viral infections as well as the rising numbers of antibiotic-resistant bacteria that have evolved as a result of the overuse of antibiotics. 2. The success of modern medicine has perhaps led to 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 through the use of vaccines. Teaching Tips 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! © 2012 Pearson Education, Inc. 53
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10.17 Viral DNA may become part of the host chromosome
2. In the Lysogenic cycle Viral DNA is inserted into the host chromosome by recombination. Viral DNA is duplicated along with the host chromosome during each cell division. Student Misconceptions and Concerns 1. Students and many parents with young children expect antibiotics to be used to treat many respiratory infections, even though such infections may result from a virus. Students will benefit from a thorough explanation of why antibiotics are inappropriate for viral infections as well as the rising numbers of antibiotic-resistant bacteria that have evolved as a result of the overuse of antibiotics. 2. The success of modern medicine has perhaps led to 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 through the use of vaccines. Teaching Tips 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! Animation: Phage Lambda Lysogenic and Lytic Cycles © 2012 Pearson Education, Inc. 54
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The phage DNA circularizes
Figure 10.17_1 Phage Attaches to cell Bacterial chromosome Phage DNA 4 The cell lyses, releasing phages 1 The phage injects its DNA Lytic cycle Figure 10.17_1 Two types of phage replication cycles (part 1) Phages assemble 2 The phage DNA circularizes 3 New phage DNA and proteins are synthesized 55
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The phage DNA circularizes
Figure 10.17_2 Phage Attaches to cell Phage DNA Bacterial chromosome The phage injects its DNA 1 7 Environmental stress Many cell divisions Lysogenic cycle Figure 10.17_2 Two types of phage replication cycles (part 2) 2 The phage DNA circularizes 6 The lysogenic bacterium replicates normally, copying the prophage at each cell division Prophage 5 Phage DNA inserts into the bacterial chromosome by recombination 56
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10.19 EVOLUTION CONNECTION: Emerging viruses threaten human health
Viruses that appear suddenly or are new to medical scientists are called emerging viruses. These include the AIDS virus, Ebola virus, West Nile virus, and SARS virus. Student Misconceptions and Concerns 1. Students and many parents with young children expect antibiotics to be used to treat many respiratory infections, even though such infections may result from a virus. Students will benefit from a thorough explanation of why antibiotics are inappropriate for viral infections as well as the rising numbers of antibiotic-resistant bacteria that have evolved as a result of the overuse of antibiotics. 2. The success of modern medicine has perhaps led to 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 through the use of vaccines. Teaching Tips 1. 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? 2. Students might wonder why a person needs to get a new seasonal flu vaccination every year. The annual mutations and variations in flu viruses require the production of a new flu vaccine annually. The Centers for Disease Control and Prevention monitors patterns of flu outbreaks, especially in Asia (where many variations of flu viruses originate). They must predict which strains are most likely to be dangerous in the coming year and then synthesize an appropriate vaccine. © 2012 Pearson Education, Inc. 57
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10.19 EVOLUTION CONNECTION: Emerging viruses threaten human health
Three processes contribute to the emergence of viral diseases: mutation—RNA viruses mutate rapidly. contact between species—viruses from other animals spread to humans. spread from isolated human populations to larger human populations, often over great distances. Student Misconceptions and Concerns 1. Students and many parents with young children expect antibiotics to be used to treat many respiratory infections, even though such infections may result from a virus. Students will benefit from a thorough explanation of why antibiotics are inappropriate for viral infections as well as the rising numbers of antibiotic-resistant bacteria that have evolved as a result of the overuse of antibiotics. 2. The success of modern medicine has perhaps led to 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 through the use of vaccines. Teaching Tips 1. 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? 2. Students might wonder why a person needs to get a new seasonal flu vaccination every year. The annual mutations and variations in flu viruses require the production of a new flu vaccine annually. The Centers for Disease Control and Prevention monitors patterns of flu outbreaks, especially in Asia (where many variations of flu viruses originate). They must predict which strains are most likely to be dangerous in the coming year and then synthesize an appropriate vaccine. © 2012 Pearson Education, Inc. 58
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10.22 Bacteria can transfer DNA in three ways
Bacteria are also valuable. Bacterial DNA is found in a single, closed loop, chromosome. Bacterial cells divide by replication of the bacterial chromosome and then by binary fission. Because binary fission is an asexual process, bacteria in a colony are genetically identical to the parent cell. Student Misconceptions and Concerns 1. Students and many parents with young children expect antibiotics to be used to treat many respiratory infections, even though such infections may result from a virus. Students will benefit from a thorough explanation of why antibiotics are inappropriate for viral infections as well as the rising numbers of antibiotic-resistant bacteria that have evolved as a result of the overuse of antibiotics. 2. The success of modern medicine has perhaps led to 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 through the use of vaccines. Teaching Tips 1. The authors note that the figures in Module represent the size of the bacterial chromosome as much smaller than they actually are. They note that a bacterial chromosome is hundreds of times longer than the cell. These chromosomes use extensive folding to fit inside the cell. 2. You might challenge students to explain why conjugation is sometimes called bacterial sex. Students might note that two organisms cooperate to produce a new, genetically unique bacterium. © 2012 Pearson Education, Inc. 59
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Recipient cell’s chromosome Recombinant chromosome
Figure 10.22D Donated DNA Crossovers Degraded DNA Figure 10.22D The integration of donated DNA into the recipient cell’s chromosome Recipient cell’s chromosome Recombinant chromosome 60
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You should now be able to
Describe the experiments of Griffith, Hershey, and Chase, which supported the idea that DNA was life’s genetic material. Compare the structures of DNA and RNA. Explain how the structure of DNA facilitates its replication. Describe the process of DNA replication. Describe the locations, reactants, and products of transcription and translation. Explain how the “languages” of DNA and RNA are used to produce polypeptides. Explain how mRNA is produced using DNA. Explain how eukaryotic RNA is processed before leaving the nucleus. Relate the structure of tRNA to its functions in the process of translation. Describe the structure and function of ribosomes. Describe the step-by-step process by which amino acids are added to a growing polypeptide chain. Diagram the overall process of transcription and translation. Describe the major types of mutations, causes of mutations, and potential consequences. Compare the lytic and lysogenic reproductive cycles of a phage. Describe three processes that contribute to the emergence of viral disease. Define a plasmid © 2012 Pearson Education, Inc. 61
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