How Genes Are Controlled Chapter 11 How Genes Are Controlled

Biology and Society: Tobacco’s Smoking Gun During the 1900s, doctors noticed that Smoking increased Lung cancer increased In 1996, researchers studying lung cancer found that, in human lung cells growing in the lab, a component of tobacco smoke, BPDE, binds to DNA within a gene called p53, which codes for a protein that normally helps suppress the formation of tumors. This work directly linked a chemical in tobacco smoke with the formation of human lung tumors. © 2010 Pearson Education, Inc.

Figure 11.00 Lung cancer x-ray

HOW AND WHY GENES ARE REGULATED Every somatic cell in an organism contains identical genetic instructions. They all share the same genome. So what makes them different? In cellular differentiation, cells become specialized in Structure Function Certain genes are turned on and off in the process of gene regulation. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Patterns of Gene Expression in Differentiated Cells In gene expression A gene is turned on and transcribed into RNA Information flows from Genes to proteins Genotype to phenotype Information flows from DNA to RNA to proteins. The great differences among cells in an organism must result from the selective expression of genes. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Pancreas cell White blood cell Nerve cell Key Active gene Gene for a Colorized TEM Colorized SEM Colorized TEM Pancreas cell White blood cell Nerve cell Gene for a glycolysis enzyme Key Antibody gene Figure 11.1 Patterns of gene expression in three types of human cells Active gene Insulin gene Hemoglobin gene Figure 11.1

Gene Regulation in Bacteria Natural selection has favored bacteria that express Only certain genes Only at specific times when the products are needed by the cell So how do bacteria selectively turn their genes on and off? An operon includes A cluster of genes with related functions The control sequences that turn the genes on or off The bacterium E. coli used the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacterium’s environment. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

The lac operon uses A promoter, a control sequence where the transcription enzyme initiates transcription An operator, a DNA segment that acts as a switch that is turned on or off A repressor, which binds to the operator and physically blocks the attachment of RNA polymerase Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Operon turned off (lactose absent) Regulatory gene Promoter Operator Genes for lactose enzymes DNA mRNA RNA polymerase cannot attach to promoter Protein Active repressor Figure 11.2a The Iac operon of E. coli: operan turned off Operon turned off (lactose absent) Figure 11.2a

Operon turned on (lactose inactivates repressor) Transcription DNA RNA polymerase bound to promoter mRNA Translation Protein Inactive repressor Lactose Figure 11.2b The Iac operon of E. coli: operan turned on Lactose enzymes Operon turned on (lactose inactivates repressor) Figure 11.2b

Gene Regulation in Eukaryotic Cells Eukaryotic cells have more complex gene regulating mechanisms with many points where the process can be regulated, as illustrated by this analogy to a water supply system with many control valves along the way. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Figure 11.3-7 Unpacking of DNA DNA Transcription of gene Processing Chromosome Unpacking of DNA DNA Gene Transcription of gene Intron Exon RNA transcript Processing of RNA Flow of mRNA through nuclear envelope Nucleus Cap Tail mRNA in nucleus Cytoplasm mRNA in cytoplasm Figure 11.3 The gene expression "pipeline" in a eukaryotic cell (Step 7) Breakdown of mRNA Translation of mRNA Polypeptide Various changes to polypeptide Active protein Breakdown of protein Figure 11.3-7

The Regulation of DNA Packing Cells may use DNA packing for long-term inactivation of genes. X chromosome inactivation Occurs in female mammals Is when one of the two X chromosomes in each cell is inactivated at random All of the descendants will have the same X chromosome turned off. If a female cat is heterozygous for a gene on the X chromosome About half her cells will express one allele The others will express the alternate allele Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Two cell populations in adult cat: Early embryo: Figure 11.4 Active X Orange fur Inactive X X chromosomes Cell division and X chromosome inactivation Allele for orange fur Allele for black fur Inactive X Black fur Figure 11.4 X chromosome inactivation: the tortoiseshell pattern on a cat Active X Figure 11.4

The Initiation of Transcription The initiation of transcription is the most important stage for regulating gene expression. In prokaryotes and eukaryotes, regulatory proteins Bind to DNA Turn the transcription of genes on and off Unlike prokaryotic genes, transcription in eukaryotes is complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Enhancers (DNA control sequences) RNA polymerase Figure 11.5 A model for the turning on of a eukaryotic gene Bend in the DNA Transcription Transcription factor Promoter Gene Figure 11.5

Repressor proteins called silencers Bind to DNA Inhibit the start of transcription Activators are More typically used by eukaryotes Turn genes on by binding to DNA Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

RNA Processing and Breakdown The eukaryotic cell Localizes transcription in the nucleus Processes RNA in the nucleus RNA processing includes the Addition of a cap and tail to the RNA Removal of any introns Splicing together of the remaining exons In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Exons DNA RNA transcript RNA splicing or mRNA 1 2 3 4 5 1 2 3 4 5 1 2 Figure 11.6 Alternative RNA splicing: producting two different mRNAs from the same gene (Step 3) RNA splicing or mRNA 1 2 3 5 1 2 4 5 Figure 11.6-3

Eukaryotic mRNAs Can last for hours to weeks to months Are all eventually broken down and their parts recycled Small single-stranded RNA molecules, called microRNAs (miRNAs), bind to complementary sequences on mRNA molecules in the cytoplasm, and some trigger the breakdown of their target mRNA. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Protein Activation and Breakdown Post-translational control mechanisms Occur after translation Often involve cutting polypeptides into smaller, active final products The selective breakdown of proteins is another control mechanism operating after translation. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Insulin (active hormone) Cutting Figure 11.7 The formation of an active insulin molecule (Step 2) Initial polypeptide Insulin (active hormone) Figure 11.7-2

Cell Signaling In a multicellular organism, gene regulation can cross cell boundaries. A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Figure 11.8-6 SIGNALING CELL Secretion Signal molecule Plasma membrane Reception Receptor protein TARGET CELL Signal transduction pathway Transcription factor (activated) Nucleus Figure 11.8 A cell-signaling pathway that turns on a gene (Step 6) Response Transcription mRNA New protein Translation Figure 11.8-6

Homeotic genes Master control genes called homeotic genes regulate groups of other genes that determine what body parts will develop in which locations. Mutations in homeotic genes can produce bizarre effects. Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Mutant fly with extra wings Mutant fly with extra legs Normal fruit fly Normal head Figure 11.9 The effect of homeotic genes Mutant fly with extra wings Mutant fly with extra legs growing from head Figure 11.9

Fruit fly embryo (10 hours) Mouse embryo (12 days) Fruit fly chromosome Mouse chromosomes Fruit fly embryo (10 hours) Mouse embryo (12 days) Figure 11.10 Homeotic genes in two different animals Adult fruit fly Adult mouse Figure 11.10

DNA Microarrays: Visualizing Gene Expression A DNA microarray allows visualization of gene expression. The pattern of glowing spots enables the researcher to determine which genes were being transcribed in the starting cells. Researchers can thus learn which genes are active in different tissues or in tissues from individuals in different states of health. Student Misconceptions and Concerns The broad concept of selective “reading” of the genetic code associated with differentiation and types of cellular activity can be missed when concentrating on the extensive details of regulation. Analogies, noted below in the teaching tips, can help students relate this overall selective process to their own experiences. Students already understand the selective reading of relevant chapters in textbooks and the selective referencing of software manuals to get answers to different questions. These experiences are similar in many ways to the broad processes of gene regulation. 2. The many levels of gene regulation in eukaryotic cells can be confusing and frustrating. The water pipe analogy depicted in Figure 11.3 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. Cellular differentiation is analogous to buying a book about how to build birdhouses and reading only the plans needed to build one particular model. Although the book contains directions to build many different birdhouses, you read and follow only the directions for the particular birdhouse you choose to build. The pages and directions for the other birdhouses remain intact. When cells differentiate, they read, or express, only the genes that are needed in that particular cell type. 2. The lactose operon is turned on by removing the repressor . . . a sort of double negative. Students might enjoy various analogies to other types of “double negatives,” such as “when the cat’s away, the mice will play.” In another analogy, if mom keeps the kids away from the cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. In this last analogy, the person occupying mom’s attention functions most like lactose binding to the repressor. 3. A key advantage of an operon system is the ability to turn off or on a set of genes with a single “switch”. You can demonstrate this relationship in your classroom by turning off or on a set of lights with a single switch. 4. The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from your local water supply, perhaps a reservoir, to a faucet in your home. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.3 illustrates the “flow” of genetic information from a chromosome—a reservoir of genetic information—to an active protein that has been made in the cell’s cytoplasm. The multiple mechanisms that control gene expression are analogous to the control valves in water pipes. In the figure, a possible control knob indicates each gene expression “valve.” In the figure, the large size of the transcription control knob highlights its crucial role. 5. Just as a folded map is difficult to read, DNA packaging tends to prevent gene “reading” or expression. 6. Just as boxes of your things that will be little used are packed deeper into a closet, attic, or basement, chromatin that is not expressed is highly compacted and is stored deeply packed away. 7. Alternative RNA splicing is like remixing music to produce a new song or reediting a movie for a different ending. 8. The action of an extracellular signal reaching a cell’s surface is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell) and activities within the house change as someone comes to answer the door. 9. Students might wonder why a patch of color is all the same on the cat’s skin in Figure 11.4, if every cell has an equal chance of being one of the two color forms. The answer is that X chromosome inactivation occurs early in development. Thus, the patch of one color represents the progeny of one embryonic cell after X chromosome inactivation. 10. Homeotic genes are often called “master control genes”. The relationship between homeotic genes and structural genes is like the relationship between a construction supervisor and the workers. Major rearrangements can result from a few simple changes in the directions for construction. 11. There is much hope in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was too often met with general treatments that benefited only a fraction of the patients. Physicians were left to wonder why some people with breast cancer or lung cancer responded to therapy while others did not. DNA microarrays allow us to identify differences between patients the same apparent type of cancer (breast, lung, prostate, etc.). Consider sharing this important avenue of hope. It is likely that some of your students will soon have a family member facing these battles.

Figure 11.11-4 mRNA isolated Reverse transcriptase and fluorescently labeled DNA nucleotides Fluorescent cDNA cDNA made from mRNA DNA microarray cDNA mixture added to wells Unbound cDNA rinsed away Nonfluorescent spot Figure 11.11 Visualizing gene expression using a DNA microarray (Step 4) Fluorescent spot Fluorescent cDNA DNA microarray (6,400 genes) DNA of an expressed gene DNA of an unexpressed gene Figure 11.11-4

CLONING PLANTS AND ANIMALS The Genetic Potential of Cells Differentiated cells All contain a complete genome Have the potential to express all of an organism’s genes Differentiated plant cells can develop into a whole new organism. Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact. © 2010 Pearson Education, Inc.

Single cell Root of carrot plant Root cells in growth medium Figure 11.12 Test-tube cloning of a carrot plant (Step 5) Root of carrot plant Root cells in growth medium Cell division in culture Young plant Adult plant Figure 11.12-5

The somatic cells of a single plant can be used to produce hundreds of thousands of clones. Plant cloning Demonstrates that cell differentiation in plants does not cause irreversible changes in the DNA Is now used extensively in agriculture Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Regeneration Is the regrowth of lost body parts Occurs, for example, in the regrowth of the legs of salamanders Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Reproductive Cloning of Animals Nuclear transplantation Involves replacing nuclei of egg cells with nuclei from differentiated cells Has been used to clone a variety of animals In 1997, Scottish researchers produced Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell in a procedure called reproductive cloning, because it results in the birth of a new animal. Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Reproductive cloning Therapeutic cloning Donor cell Nucleus from Implant embryo in surrogate mother Clone of donor is born Therapeutic cloning Remove nucleus from egg cell Add somatic cell from adult donor Grow in culture to produce an early embryo Figure 11.13 Cloning by nuclear transplantation (Step 5) Remove embryonic stem cells from embryo and grow in culture Induce stem cells to form specialized cells for therapeutic use Figure 11.13-5

Figure 11.13a Dolly and her surrogate mother

Practical Applications of Reproductive Cloning Other mammals have since been produced using this technique including Farm animals Control animals for experiments Rare animals in danger of extinction Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

(a) The first cloned cat (right) Figure 11.14a The first cloned cat (a) The first cloned cat (right) Figure 11.14a

(b) Cloning for medical use Figure 11.14b Figure 11.14b Cloning for medicinal use (b) Cloning for medical use Figure 11.14b

Human Cloning Cloning of animals Has heightened speculation about human cloning Is very difficult and inefficient Critics raise practical and ethical objections to human cloning. Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

(c) Clones of endangered animals Mouflon calf with mother Banteng Figure 11.14c Clones of endangered species Gaur Gray wolf Figure 11.14c

Therapeutic Cloning and Stem Cells The purpose of therapeutic cloning is not to produce a viable organism but to produce embryonic stem cells. Embryonic stem cells (ES cells) Are derived from blastocysts Can give rise to specific types of differentiated cells Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Adult Stem Cells Adult stem cells Are cells in adult tissues Generate replacements for nondividing differentiated cells Unlike embryonic ES cells, adult stem cells Are partway along the road to differentiation Usually give rise to only a few related types of specialized cells Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Adult stem Blood cells cells in bone marrow Nerve cells Cultured embryonic stem cells Figure 11.15 Differentiation of embryonic stem cells in culture Heart muscle cells Different culture conditions Different types of differentiated cells Figure 11.15

Umbilical Cord Blood Banking Can be collected at birth Contains partially differentiated stem cells Has had limited success in the treatment of a few diseases Student Misconceptions and Concerns 1. Students often fail to see the similarities between identical twins and cloning. Each process produces multiple individuals with identical nuclear genetic material. 2. Students often assume that clones will appear and act identically. This misunderstanding provides an opportunity to discuss the important influence of the environment in shaping the final phenotype. 3. Students might not immediately understand why reproductive cloning is necessary to transmit specific traits in farm animals. They may fail to realize that unlike cloning, sexual reproduction mixes the genetic material and may not produce offspring with the desired trait(s). Teaching Tips 1. The researchers that cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity Dolly Parton. 2. An even more remarkable aspect of salamander limb regeneration is that only the missing limb segments are regenerated. If an arm is amputated at the elbow, only the forearm, wrist, and hand are regenerated. Somehow, the cells can detect what is missing and replace only those parts! 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6–10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop into a normal individual. This technique permits embryos to be genetically screened before implanting them into a woman. However, PGD has another potential use. Researchers can use PGD to obtain embryonic stem cells without destroying a human embryo. This procedure might be more acceptable than methods that destroy the embryo to obtain embryonic stem cells. 4. The transplantation of pig or other nonhuman tissues into humans (called xenotransplantation) risks the introduction of pig (or other animal) viruses into humans. This viral DNA might not otherwise have the capacity for transmission to humans. 5. Political restrictions on the use of federal funds to study stem cells from various sources, illustrates the influence of society on the directions of science. As time permits, consider opportunities to discuss or investigate this and other ways that science and society interact.

Figure 11.16 Umbilical cord blood banking

THE GENETIC BASIS OF CANCER In recent years, scientists have learned more about the genetics of cancer. As early as 1911, certain viruses were known to cause cancer. Oncogenes are Genes that cause cancer Found in viruses Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Oncogenes and Tumor-Suppressor Genes Proto-oncogenes are Normal genes with the potential to become oncogenes Found in many animals Often genes that code for growth factors, proteins that stimulate cell division For a proto-oncogene to become an oncogene, a mutation must occur in the cell’s DNA. Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

(for protein that stimulates cell division) Proto-oncogene (for protein that stimulates cell division) DNA Mutation within the gene Multiple copies of the gene Gene moved to new DNA position, under new controls New promoter Oncogene Figure 11.17 How a proto-oncogene can become an oncogene Hyperactive growth- stimulating protein Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess Figure 11.17

Tumor-suppressor genes Inhibit cell division Prevent uncontrolled cell growth May be mutated and contribute to cancer Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Tumor-suppressor gene Mutated tumor-suppressor gene Defective, nonfunctioning protein Normal growth- inhibiting protein Cell division under control Cell division not under control Figure 11.18 Tumor-suppressor genes (a) Normal cell growth (b) Uncontrolled cell growth (cancer) Figure 11.18

The Process of Science: Can Cancer Therapy Be Personalized? Observations: Specific mutations can lead to cancer. Question: Can this knowledge be used to help patients with cancer? Hypothesis: DNA sequencing technology can be used to test tumors and identify which cancer-causing mutations they carry. Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp). © 2010 Pearson Education, Inc.

Experiment: Researchers screened for 238 possible mutations in 1,000 human tumors from 18 different body tissues. Results: No mutations are present in every tumor. Each tumor involves different mutations. It is possible to cheaply and accurately determine which mutations are present in a given cancer patient. Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Table 11.1 Cancer-causing mutations

The Progression of a Cancer Over 150,000 Americans will be stricken by cancer of the colon or rectum this year. Colon cancer Spreads gradually Is produced by more than one mutation The development of a malignant tumor is accompanied by a gradual accumulation of mutations that Convert proto-oncogenes to oncogenes Knock out tumor-suppressor genes Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Second tumor-suppressor Colon wall Cellular changes: Increased cell division Growth of benign tumor Growth of malignant tumor DNA changes: Figure 11.19 Stepwise development of a typical colon cancer (Step 3) Oncogene activated Tumor-suppressor gene inactivated Second tumor-suppressor gene inactivated Figure 11.19-3

1 mutation 2 mutations 3 mutations 4 mutations Chromosomes 1 mutation 2 mutations 3 mutations 4 mutations Figure 11.20 Accumulation of mutations in the development of a cancer cell (Step 5) Normal cell Malignant cell Figure 11.20-5

“Inherited” Cancer Most mutations that lead to cancer arise in the organ where the cancer starts. In familial or inherited cancer A cancer-causing mutation occurs in a cell that gives rise to gametes The mutation is passed on from generation to generation Breast cancer Is usually not associated with inherited mutations In some families can be caused by inherited, BRCA1 cancer genes Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Figure 11.21 Breast cancer Figure 11.21

Cancer Risk and Prevention Is one of the leading causes of death in the United States Can be caused by carcinogens, cancer-causing agents found in the environment, including Tobacco products Alcohol Exposure to ultraviolet light from the sun Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Table 11.2 Cancer in the United States (Ranked by Number of Cases)

Exposure to carcinogens Is often an individual choice Can be avoided Some studies suggest that certain substances in fruits and vegetables may help protect against a variety of cancers. Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp).

Evolution Connection: The Evolution of Cancer in the Body Evolution drives the growth of a tumor. Like individuals in a population of organisms, cancer cells in the body Have the potential to produce more offspring than can be supported by the environment Show individual variation, which Affects survival and reproduction Can be passed on to the next generation of cells Student Misconceptions and Concerns 1. Students typically have little background knowledge of cancer at the cellular level. Consider creating your own pre-test to inquire about your students entering knowledge of cancer. For example, ask students if all cancers are genetic (Yes, all cancers are based upon genetic errors and are the main subject of this chapter). In addition, ask students if exposure to a virus can lead to cancer (Yes, as noted in the text.) 2. Students often conclude falsely that most breast cancer is associated with known mutations in the breast cancer genes BRCA1 and BRCA2. However, the vast majority of breast cancer has no known inherited association. 3. Many students do not appreciate the increased risk of skin cancer and premature aging associated with the use of tanning beds. Teaching Tips 1. Tumor-suppressor genes function like the repressor in the E. coli lactose operon. The lac operon is expressed and cancers appear when their respective repressors do not function. 2. The production of a vaccine (Gardasil) against a virus known to contribute to cervical cancer has helped students become aware of the risks of HPV exposure. The following website of the National Cancer Institute describes the risks of HPV infection. (www.cancer.gov/cancertopics/factsheet/Risk/HPV) 3. Students who have had a leg, hip, or back X-rayed may recall a lead apron placed over their abdominal and pelvic region. The lead apron is to prevent the irradiation of the patient’s gonads, which could cause mutations that would be inherited. 4. Students may not realize the possible consequences of testing positive for a predisposition to cancer. Health insurance companies could use that information to deny insurance to people who are more likely to get ill. Further, people may feel obliged or be obligated to share this information with a potential mate or employer. 5. Exposure to carcinogens early in life generally carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional mutations potentially leading to disease. 6. Nearly one in five deaths in the United States results from the use of tobacco. Additional information on the risks of tobacco can be found at the following web site. (www.cancer.org/docroot/PED/content/PED_10_2X_Cigarette_Smoking_and_Cancer.asp). © 2010 Pearson Education, Inc.

Figure 11.22 X-ray of shoulder and upper arm, revealing a large bone tumor