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How Genes Are Controlled

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1 How Genes Are Controlled
Chapter 11 How Genes Are Controlled

2 Introduction Cloning is the creation of an individual by asexual reproduction. The ability to clone an animal from a single cell demonstrates that every adult body cell contains a complete genome that is capable of directing the production of all the cell types in an organism. © 2012 Pearson Education, Inc. 2

3 Introduction Cloning has been attempted to save endangered species.
Cloning has been attempted to save endangered species. However, cloning does not increase genetic diversity and may trivialize the tragedy of extinction and detract from efforts to preserve natural habitats. © 2012 Pearson Education, Inc. 3

4 Control of Gene Expression Cloning of Plants and Animals
Figure 11.0_1 Chapter 11: Big Ideas Control of Gene Expression Cloning of Plants and Animals Figure 11.0_1 Chapter 11: Big Ideas The Genetic Basis of Cancer 4

5 Figure 11.0_2 Figure 11.0_2 Cloned wolf 5

6 CONTROL OF GENE EXPRESSION
© 2012 Pearson Education, Inc. 6

7 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes Gene regulation is the turning on and off of genes. Gene expression is the overall process of information flow from genes to proteins. The control of gene expression allows cells to produce specific kinds of proteins when and where they are needed. Our earlier understanding of gene control came from the study of E. coli. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 7

8 Figure 11.1A Figure 11.1A Cells of E. coli bacteria E. coli 8

9 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes A cluster of genes with related functions, along with the control sequences, is called an operon. With few exceptions, operons only exist in prokaryotes. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 9

10 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes When an E. coli encounters lactose, all the enzymes needed for its metabolism are made at once using the lactose operon. The lactose (lac) operon includes three adjacent lactose-utilization genes, a promoter sequence where RNA polymerase binds and initiates transcription of all three lactose genes, and an operator sequence where a repressor can bind and block RNA polymerase action. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 10

11 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes Regulation of the lac operon A regulatory gene, located outside the operon, codes for a repressor protein. In the absence of lactose, the repressor binds to the operator and prevents RNA polymerase action. Lactose inactivates the repressor, so the operator is unblocked, RNA polymerase can bind to the promoter, and all three genes of the operon are transcribed. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 11

12 Operon turned off (lactose is absent): OPERON Regulatory gene
Figure 11.1B Operon turned off (lactose is absent): OPERON Regulatory gene Promoter Operator Lactose-utilization genes DNA mRNA RNA polymerase cannot attach to the promoter Protein Active repressor Operon turned on (lactose inactivates the repressor): Figure 11.1B The lac operon DNA RNA polymerase is bound to the promoter mRNA Translation Protein Inactive repressor Lactose Enzymes for lactose utilization 12

13 Operon turned off (lactose is absent): OPERON Regulatory gene
Figure 11.1B_1 Operon turned off (lactose is absent): OPERON Regulatory gene Promoter Operator Lactose-utilization genes DNA mRNA RNA polymerase cannot attach to the promoter Protein Active repressor Figure 11.1B_1 The lac operon (part 1) 13

14 Operon turned on (lactose inactivates the repressor):
Figure 11.1B_2 Operon turned on (lactose inactivates the repressor): DNA RNA polymerase is bound to the promoter mRNA Translation Protein Figure 11.1B_2 The lac operon (part 2) Inactive repressor Lactose Enzymes for lactose utilization 14

15 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes There are two types of repressor-controlled operons. In the lac operon, the repressor is active when alone and inactive when bound to lactose. In the trp bacterial operon, the repressor is inactive when alone and active when bound to the amino acid tryptophan (Trp). Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 15

16 lac operon trp operon DNA Active repressor Active repressor Tryptophan
Figure 11.1C lac operon trp operon Promoter Operator Gene DNA Active repressor Active repressor Tryptophan Figure 11.1C Two types of repressor-controlled operons Inactive repressor Inactive repressor Lactose 16

17 11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes Another type of operon control involves activators, proteins that turn operons on by binding to DNA and making it easier for RNA polymerase to bind to the promoter. Activators help control a wide variety of operons. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The lactose operon is turned on by removing the repressor a sort of double negative. Students might enjoy various analogies to other situations, including the familiar refrain “When the cat's away, the mice will play.” Like a cat watching mice, if a mom keeps her kids away from cookies, but somebody occupies her attention, kids can sneak by and snatch some cookies. Thus, the person occupying Mom’s attention functions most like lactose binding to the repressor. 2. 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. 3. The control of gene expression 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. © 2012 Pearson Education, Inc. 17

18 11.2 Chromosome structure and chemical modifications can affect gene expression
Differentiation involves cell specialization, in structure and function, and is controlled by turning specific sets of genes on or off. Almost all of the cells in an organism contain an identical genome. The differences between cell types are not due to the presence of different genes but instead due to selective gene expression. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 18

19 11.2 Chromosome structure and chemical modifications can affect gene expression
Eukaryotic chromosomes undergo multiple levels of folding and coiling, called DNA packing. Nucleosomes are formed when DNA is wrapped around histone proteins. This packaging gives a “beads on a string” appearance. Each nucleosome bead includes DNA plus eight histones. Stretches of DNA, called linkers, join consecutive nucleosomes. At the next level of packing, the beaded string is wrapped into a tight helical fiber. This fiber coils further into a thick supercoil. Looping and folding can further compact the DNA. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 19

20 11.2 Chromosome structure and chemical modifications can affect gene expression
DNA packing can prevent gene expression by preventing RNA polymerase and other transcription proteins from contacting the DNA. Cells seem to use higher levels of packing for long-term inactivation of genes. Highly compacted chromatin, found in varying regions of interphase chromosomes, is generally not expressed at all. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 20

21 Animation: DNA Packing
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. Animation: DNA Packing Right click on animation / Click play © 2012 Pearson Education, Inc. 21

22 11.2 Chromosome structure and chemical modifications can affect gene expression
Chemical modification of DNA bases or histone proteins can result in epigenetic inheritance. Certain enzymes can add a methyl group to DNA bases, without changing the sequence of the bases. Individual genes are usually more methylated in cells in which the genes are not expressed. Once methylated, genes usually stay that way through successive cell divisions in an individual. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 22

23 11.2 Chromosome structure and chemical modifications can affect gene expression
Removal of the extra methyl groups can turn on some of these genes. Inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence is called epigenetic inheritance. These modifications can be reversed by processes not yet fully understood. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 23

24 11.2 Chromosome structure and chemical modifications can affect gene expression
X-chromosome inactivation In female mammals, one of the two X chromosomes is highly compacted and transcriptionally inactive. Either the maternal or paternal chromosome is randomly inactivated. Inactivation occurs early in embryonic development, and all cellular descendants have the same inactivated chromosome. An inactivated X chromosome is called a Barr body. Tortoiseshell fur coloration is due to inactivation of X chromosomes in heterozygous female cats. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The control of gene expression 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. Just as boxes of things that you rarely use are packed into a closet, attic, or basement, chromatin that is not expressed is highly compacted, and stored deeply packed away. 3. Just as a folded map is difficult to read, DNA packaging tends to prevent gene reading or expression. 4. Students might wonder why a patch of color is all the same on a cat’s skin 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. © 2012 Pearson Education, Inc. 24

25 DNA double helix (2-nm diameter)
Figure 11.2A DNA double helix (2-nm diameter) Metaphase chromosome Nucleosome (10-nm diameter) Tight helical fiber (30-nm diameter) Linker “Beads on a string” Figure 11.2A DNA packing in a eukaryotic chromosome Supercoil (300-nm diameter) Histones 700 nm 25

26 “Beads on a string” Linker Figure 11.2A_1
Figure 11.2A_1 DNA packing in a eukaryotic chromosome (beads on a string) 26

27 Metaphase chromosome 700 nm Figure 11.2A_2
Figure 11.2A_2 DNA packing in a eukaryotic chromosome (metaphase chromosome) 700 nm 27

28 Cell division and random X chromosome inactivation
Figure 11.2B Early Embryo Adult Two cell populations Cell division and random X chromosome inactivation X chromo- somes Active X Orange fur Inactive X Figure 11.2B A tortoiseshell pattern on a female cat, a result of X chromosome inactivation Allele for orange fur Inactive X Allele for black fur Active X Black fur 28

29 Figure 11.2B_2 Figure 11.2B_2 A tortoiseshell pattern on a female cat, a result of X chromosome inactivation (part 2) 29

30 Cell division and random X chromosome inactivation
Figure 11.2B_1 Early Embryo Adult Two cell populations Cell division and random X chromosome inactivation X chromo- somes Active X Orange fur Inactive X Inactive X Figure 11.2B_1 A tortoiseshell pattern on a female cat, a result of X chromosome inactivation (part 1) Allele for orange fur Allele for black fur Active X Black fur 30

31 11.3 Complex assemblies of proteins control eukaryotic transcription
Prokaryotes and eukaryotes employ regulatory proteins (activators and repressors) that bind to specific segments of DNA and either promote or block the binding of RNA polymerase, turning the transcription of genes on and off. In eukaryotes, activator proteins seem to be more important than repressors. Thus, the default state for most genes seems to be off. A typical plant or animal cell needs to turn on and transcribe only a small percentage of its genes. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope. © 2012 Pearson Education, Inc. 31

32 11.3 Complex assemblies of proteins control eukaryotic transcription
Eukaryotic RNA polymerase requires the assistance of proteins called transcription factors. Transcription factors include activator proteins, which bind to DNA sequences called enhancers and initiate gene transcription. The binding of the activators leads to bending of the DNA. Other transcription factor proteins interact with the bound activators, which then collectively bind as a complex at the gene’s promoter. RNA polymerase then attaches to the promoter and transcription begins. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope. © 2012 Pearson Education, Inc. 32

33 Animation: Initiation of Transcription
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope. Animation: Initiation of Transcription Right click on animation / Click play © 2012 Pearson Education, Inc. 33

34 Transcription factors
Figure 11.3 Enhancers Promoter Gene DNA Activator proteins Transcription factors Other proteins RNA polymerase Figure 11.3 A model for the turning on of a eukaryotic gene Bending of DNA Transcription 34

35 11.3 Complex assemblies of proteins control eukaryotic transcription
Silencers are repressor proteins that may bind to DNA sequences and inhibit transcription. Coordinated gene expression in eukaryotes often depends on the association of a specific combination of control elements with every gene of a particular metabolic pathway. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors note that the selective unpackaging of chromosomes is the “coarse adjustment” of eukaryotic gene expression. The initiation of RNA synthesis is the fine-tuning of the regulation. If you have recently asked your students to use microscopes in lab, you might relate these degrees of adjustment to the coarse and fine control knobs of a microscope. © 2012 Pearson Education, Inc. 35

36 11.4 Eukaryotic RNA may be spliced in more than one way
Alternative RNA splicing produces different mRNAs from the same transcript, results in the production of more than one polypeptide from the same gene, and may be common in humans. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips Alternative RNA splicing is like remixing music to produce a new song or re-editing a movie for a different effect. © 2012 Pearson Education, Inc. 36

37 Animation: RNA Processing
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips Alternative RNA splicing is like remixing music to produce a new song or re-editing a movie for a different effect. Animation: RNA Processing Right click on animation / Click play © 2012 Pearson Education, Inc. 37

38 Exons DNA 1 2 3 4 5 Introns Introns Cap Tail RNA transcript 1 2 3 4 5
Figure 11.4 Exons DNA 1 2 3 4 5 Introns Introns Cap Tail RNA transcript 1 2 3 4 5 RNA splicing Figure 11.4 The production of two different mRNAs from the same gene or mRNA 1 2 3 5 1 2 4 5 38

39 11.5 Small RNAs play multiple roles in controlling gene expression
Only about 1.5% of the human genome codes for proteins. (This is also true of many other multicellular eukaryotes.) Another small fraction of DNA consists of genes for ribosomal RNA and transfer RNA. A flood of recent data suggests that a significant amount of the remaining genome is transcribed into functioning but non-protein-coding RNAs, including a variety of small RNAs. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. References in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as junk DNA. The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence! 2. Describing the discovery of miRNAs and their potential in research and medicine helps to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers. © 2012 Pearson Education, Inc. 39

40 11.5 Small RNAs play multiple roles in controlling gene expression
microRNAs (miRNAs) can bind to complementary sequences on mRNA molecules either degrading the target mRNA or blocking its translation. RNA interference (RNAi) is the use of miRNA to artificially control gene expression by injecting miRNAs into a cell to turn off a specific gene sequence. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. References in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as junk DNA. The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence! 2. Describing the discovery of miRNAs and their potential in research and medicine helps to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers. © 2012 Pearson Education, Inc. 40

41 Animation: Blocking Translation
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. References in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as junk DNA. The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence! 2. Describing the discovery of miRNAs and their potential in research and medicine helps to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers. Animation: Blocking Translation Right click on animation / Click play © 2012 Pearson Education, Inc. 41

42 Animation: mRNA Degradation
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. References in older books and outdated websites may characterize DNA that does not code for rRNA, tRNA, or mRNA as junk DNA. The relatively recent discovery of miRNA and its significant roles in gene regulation reveals the danger of concluding that the absence of evidence is evidence of absence! 2. Describing the discovery of miRNAs and their potential in research and medicine helps to illustrate the promise of gene regulation research. Students early in their science careers may appreciate knowing about scientific fields with great potential as they consider the direction of their developing careers. Animation: mRNA Degradation Right click on animation / Click play © 2012 Pearson Education, Inc. 42

43 miRNA- protein complex
Figure 11.5 Protein miRNA 1 miRNA- protein complex 2 Target mRNA Figure 11.5 Mechanisms of RNA interference 3 or 4 Translation blocked mRNA degraded 43

44 11.6 Later stages of gene expression are also subject to regulation
After mRNA is fully processed and transported to the cytoplasm, gene expression can still be regulated by breakdown of mRNA, initiation of translation, protein activation, and protein breakdown. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. © 2012 Pearson Education, Inc. 44

45 Initial polypeptide (inactive) Folded polypeptide (inactive)
Figure 11.6 SH SH Folding of the polypeptide and the formation of S—S linkages S S S S SH S Cleavage S SH SH S S SH S S S S Initial polypeptide (inactive) Folded polypeptide (inactive) Active form of insulin Figure 11.6 Protein activation: the role of polypeptide cleavage 45

46 Initial polypeptide (inactive) Folded polypeptide (inactive)
Figure 11.6_1 SH SH Folding of the polypeptide and the formation of S—S linkages S S SH S SH SH S S SH S Figure 11.6_1 Protein activation: the role of polypeptide cleavage (part 1) Initial polypeptide (inactive) Folded polypeptide (inactive) 46

47 Folded polypeptide (inactive)
Figure 11.6_2 S S S S Cleavage S S S S S S S S Figure 11.6_2 Protein activation: the role of polypeptide cleavage (part 2) Active form of insulin Folded polypeptide (inactive) 47

48 11.7 Review: Multiple mechanisms regulate gene expression in eukaryotes
Multiple control points exist where gene expression in eukaryotes can be turned on or off or speeded up, or slowed down. These control points are like a series of pipes carrying water from your local water supply to a faucet in your home. Valves in this series of pipes are like the control points in gene expression. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. © 2012 Pearson Education, Inc. 48

49 Animation: Protein Degradation
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. Animation: Protein Degradation Right click on animation / Click play © 2012 Pearson Education, Inc. 49

50 Animation: Protein Processing
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. Animation: Protein Processing Right click on animation / Click play © 2012 Pearson Education, Inc. 50

51 Figure 11.7 The gene expression “pipeline” in a eukaryotic cell
Chromosome Chromosome DNA unpacking Other changes to the DNA Gene DNA Transcription Gene Exon RNA transcript Intron Addition of a cap and tail Splicing Tail Cap mRNA in nucleus Flow through nuclear envelope NUCLEUS CYTOPLASM mRNA in cytoplasm Breakdown of mRNA Broken- down mRNA Translation Figure 11.7 The gene expression “pipeline” in a eukaryotic cell Polypeptide Polypeptide Cleavage, modification, activation Active protein Active protein Breakdown of protein Amino acids 51

52 DNA unpacking Other changes to the DNA
Figure 11.7_1 Chromosome Chromosome DNA unpacking Other changes to the DNA DNA Gene Gene Transcription Exon RNA transcript Intron Addition of a cap and tail Figure 11.7_1 The gene expression “pipeline” in a eukaryotic cell (part 1) Splicing Tail Cap mRNA in nucleus Flow through nuclear envelope NUCLEUS CYTOPLASM 52

53 Cleavage, modification, activation
Figure 11.7_2 CYTOPLASM mRNA in cytoplasm Breakdown of mRNA Broken- down mRNA Translation Polypeptide Polypeptide Cleavage, modification, activation Active protein Active protein Figure 11.7_2 The gene expression “pipeline” in a eukaryotic cell (part 2) Breakdown of protein Amino acids 53

54 11.7 Review: Multiple mechanisms regulate gene expression in eukaryotes
These controls points include: chromosome changes and DNA unpacking, control of transcription, control of RNA processing including the addition of a cap and tail and splicing, flow through the nuclear envelope, breakdown of mRNA, Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. © 2012 Pearson Education, Inc. 54

55 11.7 Review: Multiple mechanisms regulate gene expression in eukaryotes
control of translation, and control after translation including cleavage/modification/activation of proteins and breakdown of protein. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips The authors develop an analogy between the regulation of transcription and the series of water pipes that carry water from a local water supply, perhaps a reservoir, to a faucet. At various points, valves control the flow of water. Similarly, the expression of genes is controlled at many points along the process. Figure 11.7 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.” The larger size of the transcription control knob highlights its crucial role. © 2012 Pearson Education, Inc. 55

56 11.8 Cell signaling and cascades of gene expression direct animal development
Early research on gene expression and embryonic development came from studies of a fruit fly, revealing the control of these key events. Orientation of the head-to-tail, top-to-bottom, and side-to-side axes are determined by early genes in the egg that produce proteins and maternal mRNAs. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 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. © 2012 Pearson Education, Inc. 56

57 Animation: Cell Signaling
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 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. Animation: Cell Signaling Right click on animation / Click play © 2012 Pearson Education, Inc. 57

58 Animation: Development of Head-Tail Axis in Fruit Flies
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 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. Animation: Development of Head-Tail Axis in Fruit Flies Right click on animation / Click play © 2012 Pearson Education, Inc. 58

59 11.8 Cell signaling and cascades of gene expression direct animal development
Segmentation of the body is influenced by cascades of proteins that diffuse through the cell layers. Adult features develop under the influence of homeotic genes, master control genes that determine the anatomy of the parts of the body. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 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. © 2012 Pearson Education, Inc. 59

60 Eye Antenna Extra pair of legs Figure 11.8A
Figure 11.8A A normal fruit fly (left) compared with a mutant fruit fly (right) with legs coming out of its head Extra pair of legs 60

61 Figure 11.8A_1 Eye Antenna Figure 11.8A_1 A normal fruit fly compared with a mutant fruit fly with legs coming out of its head (part 1) 61

62 Extra pair of legs Figure 11.8A_2
Figure 11.8A_2 A normal fruit fly compared with a mutant fruit fly with legs coming out of its head (part 2) Extra pair of legs 62

63 Egg cell within ovarian follicle
Figure 11.8B Egg cell within ovarian follicle Egg cell Egg cell and follicle cells signaling each other 1 Follicle cells Gene expression Growth of egg cell Localization of “head” mRNA 2 Egg cell “Head” mRNA Cascades of gene expression Fertilization and mitosis Embryo Body segments Figure 11.8B Key steps in the early development of head-tail axis in a fruit fly 3 Expression of homeotic genes and cascades of gene expression Adult fly 4 63

64 Egg cell within ovarian follicle
Figure 11.8B_1 Egg cell within ovarian follicle Egg cell Egg cell and follicle cells signaling each other 1 Follicle cells Gene expression Growth of egg cell Localization of “head” mRNA 2 Egg cell Figure 11.8B_1 Key steps in the early development of head-tail axis in a fruit fly (part 1) “Head” mRNA Cascades of gene expression Fertilization and mitosis 64

65 Expression of homeotic genes and cascades of gene expression
Figure 11.8B_2 Embryo Body segments 3 Expression of homeotic genes and cascades of gene expression Adult fly Figure 11.8B_2 Key steps in the early development of head-tail axis in a fruit fly (part 2) 4 65

66 11.9 CONNECTION: DNA microarrays test for the transcription of many genes at once
DNA microarrays help researchers study the expression of large groups of genes. A DNA microarray contains DNA sequences arranged on a grid and is used to test for transcription in the following way: mRNA from a specific cell type is isolated, fluorescent cDNA is produced from the mRNA, cDNA is applied to the microarray, unbound cDNA is washed off, and complementary cDNA is detected by fluorescence. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips There is much promise in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was met with general treatments that benefited only a small 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 within each type of cancer (breast, lung, prostate, etc.). Consider sharing this important source of hope. It is likely that some of your students will soon have a family member facing these battles. © 2012 Pearson Education, Inc. 66

67 Figure 11.9 A DNA microarray
Each well contains DNA from a particular gene. Actual size (6,400 genes) 1 mRNA is isolated. 4 Unbound cDNA is rinsed away. Reverse transcriptase and fluorescent DNA nucleotides Fluorescent spot Nonfluorescent spot 3 cDNA is applied to the wells. 2 cDNA is made from mRNA. cDNA Figure 11.9 A DNA microarray DNA of an expressed gene DNA of an unexpressed gene 67

68 Reverse transcriptase and fluorescent DNA nucleotides
Figure 11.9_1 1 mRNA is isolated. Reverse transcriptase and fluorescent DNA nucleotides Figure 11.9_1 A DNA microarray (part 1) 2 cDNA is made from mRNA. 68

69 Each well contains DNA from a particular gene.
Figure 11.9_2 DNA microarray Each well contains DNA from a particular gene. Actual size (6,400 genes) 4 Unbound cDNA is rinsed away. Fluorescent spot Nonfluorescent spot 3 cDNA is applied to the wells. Figure 11.9_2 A DNA microarray (part 2) cDNA DNA of an expressed gene DNA of an unexpressed gene 69

70 11.9 CONNECTION: DNA microarrays test for the transcription of many genes at once
DNA microarrays are a potential boon to medical research. In 2002, a study showed that DNA microarray data can classify different types of leukemia, helping to identify which chemotherapies will be most effective. Other research suggests that many cancers have a variety of subtypes with different gene expression patterns. DNA microarrays also reveal general profiles of gene expression over the lifetime of an organism. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips There is much promise in the use of DNA microarrays to refine cancer therapies. In the past, a diagnosis of cancer was met with general treatments that benefited only a small 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 within each type of cancer (breast, lung, prostate, etc.). Consider sharing this important source of hope. It is likely that some of your students will soon have a family member facing these battles. © 2012 Pearson Education, Inc. 70

71 11.10 Signal transduction pathways convert messages received at the cell surface to responses within the cell A signal transduction pathway is a series of molecular changes that convert a signal on the target cell’s surface to a specific response within the cell. Signal transduction pathways are crucial to many cellular functions. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The authors note that signal transduction pathways were addressed in Module 8.8 and will again be addressed as these pathways are involved in controlling hormone functions in animals in Chapter 26 and in plants in Chapter 33. If your course does not include these other chapters, consider investing some of these aspects into the Chapter 11 materials. 2. The action of an extracellular signal reaching a cell’s surface in a signal transduction pathway is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell), and activities change within the house as someone comes to answer the door. 3. Some of the stages of a signal transduction pathway can be compared to a human reaction. Consider someone calling your name. (1) Reception—The sound waves of someone’s voice hitting and changing the shape of your eardrum. (2) Transduction—Your ear converts sound waves to nerve impulses and sends a signal to your brain that your name has been called. (3) Response—You look around to see who is calling. © 2012 Pearson Education, Inc. 71

72 Animation: Overview of Cell Signaling
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The authors note that signal transduction pathways were addressed in Module 8.8 and will again be addressed as these pathways are involved in controlling hormone functions in animals in Chapter 26 and in plants in Chapter 33. If your course does not include these other chapters, consider investing some of these aspects into the Chapter 11 materials. 2. The action of an extracellular signal reaching a cell’s surface in a signal transduction pathway is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell), and activities change within the house as someone comes to answer the door. 3. Some of the stages of a signal transduction pathway can be compared to a human reaction. Consider someone calling your name. (1) Reception—The sound waves of someone’s voice hitting and changing the shape of your eardrum. (2) Transduction—Your ear converts sound waves to nerve impulses and sends a signal to your brain that your name has been called. (3) Response—You look around to see who is calling. Animation: Overview of Cell Signaling Right click on animation / Click play © 2012 Pearson Education, Inc. 72

73 Animation: Signal Transduction Pathways
Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. The authors note that signal transduction pathways were addressed in Module 8.8 and will again be addressed as these pathways are involved in controlling hormone functions in animals in Chapter 26 and in plants in Chapter 33. If your course does not include these other chapters, consider investing some of these aspects into the Chapter 11 materials. 2. The action of an extracellular signal reaching a cell’s surface in a signal transduction pathway is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell), and activities change within the house as someone comes to answer the door. 3. Some of the stages of a signal transduction pathway can be compared to a human reaction. Consider someone calling your name. (1) Reception—The sound waves of someone’s voice hitting and changing the shape of your eardrum. (2) Transduction—Your ear converts sound waves to nerve impulses and sends a signal to your brain that your name has been called. (3) Response—You look around to see who is calling. Animation: Signal Transduction Pathways Right click on animation / Click play © 2012 Pearson Education, Inc. 73

74 Signal transduction pathway
Figure 11.10 Signaling cell EXTRACELLULAR FLUID Signaling molecule 1 Receptor protein Plasma membrane 2 Target cell 3 Relay proteins Signal transduction pathway 4 Transcription factor (activated) NUCLEUS Figure A signal transduction pathway that turns on a gene DNA 5 Transcription mRNA New protein 6 CYTOPLASM Translation 74

75 Signal transduction pathway
Figure 11.10_1 Signaling cell EXTRACELLULAR FLUID Signaling molecule 1 Receptor protein Plasma membrane 2 Target cell 3 Relay proteins Signal transduction pathway Figure 11.10_1 A signal transduction pathway that turns on a gene (part 1) 75

76 Transcription factor (activated)
Figure 11.10_2 4 Transcription factor (activated) NUCLEUS DNA 5 Transcription mRNA Figure 11.10_2 A signal transduction pathway that turns on a gene (part 2) New protein 6 Translation CYTOPLASM 76

77 11.11 EVOLUTION CONNECTION: Cell-signaling systems appeared early in the evolution of life
In the yeast used to make bread, beer, and wine, mating is controlled by a signal transduction pathway. These yeast cells identify their mates by chemical signaling. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. As François Jacob suggested, evolution works as a tinkerer and not like an engineer. New forms evolve by remodeling old forms. As the text notes, cell signaling mechanisms likely evolved first in ancient prokaryotes and then became adapted for new functions in their multicellular descendants. Examples of remodeling might be a subject you may want to explore in additional detail as an important lesson in evolution. 2. The action of an extracellular signal reaching a cell’s surface in a signal transduction pathway is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell), and activities change within the house as someone comes to answer the door. 3. Some of the stages of a signal transduction pathway can be compared to a human reaction. Consider someone calling your name. (1) Reception—The sound waves of someone’s voice hitting and changing the shape of your eardrum. (2) Transduction—Your ear converts sound waves to nerve impulses and sends a signal to your brain that your name has been called. (3) Response—You look around to see who is calling. © 2012 Pearson Education, Inc. 77

78 11.11 EVOLUTION CONNECTION: Cell-signaling systems appeared early in the evolution of life
Yeast have two mating types: a and . Each produces a chemical factor that binds to receptors on cells of the opposite mating type. Binding to receptors triggers growth toward the other cell and fusion. Cell signaling processes in multicellular organisms are derived from those in unicellular organisms such as bacteria and yeast. Student Misconceptions and Concerns 1. 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 11.7 can be a helpful reference to organize the potential sites of regulation. Teaching Tips 1. As François Jacob suggested, evolution works as a tinkerer and not like an engineer. New forms evolve by remodeling old forms. As the text notes, cell signaling mechanisms likely evolved first in ancient prokaryotes and then became adapted for new functions in their multicellular descendants. Examples of remodeling might be a subject you may want to explore in additional detail as an important lesson in evolution. 2. The action of an extracellular signal reaching a cell’s surface in a signal transduction pathway is like pushing the doorbell at a home. The signal is converted to another form (pushing a button rings a bell), and activities change within the house as someone comes to answer the door. 3. Some of the stages of a signal transduction pathway can be compared to a human reaction. Consider someone calling your name. (1) Reception—The sound waves of someone’s voice hitting and changing the shape of your eardrum. (2) Transduction—Your ear converts sound waves to nerve impulses and sends a signal to your brain that your name has been called. (3) Response—You look around to see who is calling. © 2012 Pearson Education, Inc. 78

79 Yeast cell, mating type a Yeast cell, mating type 
Figure 11.11 Receptor  factor a Yeast cell, mating type a Yeast cell, mating type  a factor a Figure Communication between mating yeast cells a/ 79

80 CLONING OF PLANTS AND ANIMALS
© 2012 Pearson Education, Inc. 80

81 11.12 Plant cloning shows that differentiated cells may retain all of their genetic potential
Most differentiated cells retain a full set of genes, even though only a subset may be expressed. Evidence is available from plant cloning, in which a root cell can divide to form an adult plant and salamander limb regeneration, in which the cells in the leg stump dedifferentiate, divide, and then redifferentiate, giving rise to a new leg. 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. Teaching Tips 1. The basic question asked in Module is whether a cell becomes differentiated by selectively reading the genome or by retaining only the needed sections. In your course, you are unlikely to assign the entire Concepts textbook. Instead, you will likely ask your students to selectively read chapters in the book. Students could remove all of the pages that they do not need, leaving only those assigned. Alternately, students could keep their textbooks intact, reading only the assigned and relevant passages. These latter students, with intact textbooks, behave like cells undergoing differentiation. 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! © 2012 Pearson Education, Inc. 81

82 Root cells cultured in growth medium Cell division in culture
Figure 11.12 Root of carrot plant Single cell Figure Growth of a carrot plant from a differentiated root cell Root cells cultured in growth medium Cell division in culture Plantlet Adult plant 82

83 11.13 Nuclear transplantation can be used to clone animals
Animal cloning can be achieved using nuclear transplantation, in which the nucleus of an egg cell or zygote is replaced with a nucleus from an adult somatic cell. Using nuclear transplantation to produce new organisms is called reproductive cloning. It was first used in mammals in 1997 to produce the sheep Dolly. 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. Teaching Tips 1. The researchers who cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity country singer Dolly Parton. 2. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 83

84 11.13 Nuclear transplantation can be used to clone animals
Another way to clone uses embryonic stem (ES) cells harvested from a blastocyst. This procedure can be used to produce cell cultures for research or stem cells for therapeutic treatments. 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. Teaching Tips 1. The researchers who cloned Dolly the sheep from a mammary gland cell named Dolly after the celebrity country singer Dolly Parton. 2. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 84

85 Figure 11.13 Nuclear transplantation for cloning
Donor cell Nucleus from the donor cell Reproductive cloning Blastocyst The blastocyst is implanted in a surrogate mother. A clone of the donor is born. The nucleus is removed from an egg cell. A somatic cell from an adult donor is added. The cell grows in culture to produce an early embryo (blastocyst). Therapeutic cloning Embryonic stem cells are removed from the blastocyst and grown in culture. The stem cells are induced to form specialized cells. Figure Nuclear transplantation for cloning 85

86 The nucleus is removed from an egg cell.
Figure 11.13_1 Donor cell Nucleus from the donor cell Blastocyst The nucleus is removed from an egg cell. A somatic cell from an adult donor is added. The cell grows in culture to produce an early embryo (blastocyst). Figure 11.13_1 Nuclear transplantation for cloning (part 1) 86

87 The blastocyst is implanted in a surrogate mother.
Figure 11.13_2 Reproductive cloning Blastocyst The blastocyst is implanted in a surrogate mother. A clone of the donor is born. Therapeutic cloning Figure 11.13_2 Nuclear transplantation for cloning (part 2) Embryonic stem cells are removed from the blastocyst and grown in culture. The stem cells are induced to form specialized cells. 87

88 11.14 CONNECTION: Reproductive cloning has valuable applications, but human reproductive cloning raises ethical issues Since Dolly’s landmark birth in 1997, researchers have cloned many other mammals, including mice, cats, horses, cows, mules, pigs, rabbits, ferrets, and dogs. Cloned animals can show differences in anatomy and behavior due to environmental influences and random phenomena. 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. Teaching Tips 1. 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). 2. 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. 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 88

89 11.14 CONNECTION: Reproductive cloning has valuable applications, but human reproductive cloning raises ethical issues Reproductive cloning is used to produce animals with desirable traits to produce better agricultural products, produce therapeutic agents, and restock populations of endangered animals. Human reproductive cloning raises many ethical concerns. 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. Teaching Tips 1. 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). 2. 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. 3. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 89

90 Figure 11.14 Figure CC, the world’s first cloned cat (right), and her lone parent (left) 90

91 11.15 CONNECTION: Therapeutic cloning can produce stem cells with great medical potential
When grown in laboratory culture, stem cells can divide indefinitely and give rise to many types of differentiated cells. Adult stem cells can give rise to many, but not all, types of 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. Teaching Tips 1. The political restrictions on the use of federal funds to study stem cells illustrate 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. 2. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 91

92 11.15 CONNECTION: Therapeutic cloning can produce stem cells with great medical potential
Embryonic stem cells are considered more promising than adult stem cells for medical applications. The ultimate aim of therapeutic cloning is to supply cells for the repair of damaged or diseased organs. 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. Teaching Tips 1. The political restrictions on the use of federal funds to study stem cells illustrate 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. 2. Preimplantation genetic diagnosis (PGD) is a genetic screening technique that removes one or two cells from an embryo at about the 6 to 10 cell stage. The cells that are removed are genetically analyzed while the remaining embryonic cell mass retains the potential to develop. 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. © 2012 Pearson Education, Inc. 92

93 Adult stem cells in bone marrow Cultured embryonic stem cells
Figure 11.15 Blood cells Adult stem cells in bone marrow Nerve cells Cultured embryonic stem cells Figure Differentiation of stem cells in culture Heart muscle cells Different culture conditions Different types of differentiated cells 93

94 THE GENETIC BASIS OF CANCER
© 2012 Pearson Education, Inc. 94

95 11.16 Cancer results from mutations in genes that control cell division
Mutations in two types of genes can cause cancer. Oncogenes Proto-oncogenes are normal genes that promote cell division. Mutations to proto-oncogenes create cancer-causing oncogenes that often stimulate cell division. Tumor-suppressor genes Tumor-suppressor genes normally inhibit cell division or function in the repair of DNA damage. Mutations inactivate the genes and allow uncontrolled division to occur. Student Misconceptions and Concerns 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. (Answer: yes, as noted in Module 11.16). 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 website of the National Cancer Institute describes the risks of HPV infection at © 2012 Pearson Education, Inc. 95

96 Proto-oncogene (for a protein that stimulates cell division)
Figure 11.16A Proto-oncogene (for a protein that stimulates cell division) DNA A mutation within the gene Multiple copies of the gene The gene is moved to a new DNA locus, under new controls Oncogene New promoter Figure 11.16A Alternative ways to make oncogenes from a proto-oncogene (all leading to excessive cell growth) Hyperactive growth- stimulating protein in a normal amount Normal growth- stimulating protein in excess Normal growth- stimulating protein in excess 96

97 Tumor-suppressor gene Mutated tumor-suppressor gene
Figure 11.16B Tumor-suppressor gene Mutated tumor-suppressor gene Normal growth- inhibiting protein Defective, nonfunctioning protein Cell division not under control Cell division under control Figure 11.16B The effect of a mutation in a tumor-suppressor gene 97

98 11.17 Multiple genetic changes underlie the development of cancer
Usually four or more somatic mutations are required to produce a full-fledged cancer cell. One possible scenario is the stepwise development of colorectal cancer. An oncogene arises or is activated, resulting in increased cell division in apparently normal cells in the colon lining. Additional DNA mutations cause the growth of a small benign tumor (polyp) in the colon wall. Additional mutations lead to a malignant tumor with the potential to metastasize. Teaching Tips Exposure to carcinogens early in life carries greater risks than the same exposure later in life. This is because damage in early life has more time to accumulate additional changes, potentially leading to disease. © 2012 Pearson Education, Inc. 98

99 An oncogene is activated A tumor-suppressor gene is inactivated
Figure 11.17A DNA changes: An oncogene is activated A tumor-suppressor gene is inactivated A second tumor- suppressor gene is inactivated Cellular changes: Increased cell division Growth of a polyp Growth of a malignant tumor 1 2 3 Figure 11.17A Stepwise development of a typical colon cancer Colon wall 99

100 1 mutation 2 mutations 3 mutations 4 mutations Chromosomes Normal cell
Figure 11.17B 1 mutation 2 mutations 3 mutations 4 mutations Chromosomes Normal cell Malignant cell Figure 11.17B Accumulation of mutations in the development of a cancer cell 100

101 11.18 Faulty proteins can interfere with normal signal transduction pathways
Proto-oncogenes and tumor-suppressor genes often code for proteins involved in signal transduction pathways leading to gene expression. Two main types of signal transduction pathways lead to the synthesis of proteins that influence cell division. Teaching Tips Mutations in the ras or p53 genes are like having car problems in which the gas pedal overaccelerates or the brakes on the car fail to function. In either situation, an accident is more likely to occur. © 2012 Pearson Education, Inc. 101

102 11.18 Faulty proteins can interfere with normal signal transduction pathways
One pathway produces a product that stimulates cell division. In a healthy cell, the product of the ras proto-oncogene relays a signal when growth factor binds to a receptor. But in a cancerous condition, the product of the ras proto-oncogene relays the signal in the absence of a growth factor, leading to uncontrolled growth. Mutations in ras occur in more than 30% of human cancers. Teaching Tips Mutations in the ras or p53 genes are like having car problems in which the gas pedal overaccelerates or the brakes on the car fail to function. In either situation, an accident is more likely to occur. © 2012 Pearson Education, Inc. 102

103 Normal product of ras gene
Figure 11.18A Growth factor Receptor Target cell Hyperactive relay protein (product of ras oncogene) issues signals on its own Normal product of ras gene Relay proteins Transcription factor (activated) CYTOPLASM Figure 11.18A A stimulatory signal transduction pathway and the effect of an oncogene protein DNA NUCLEUS Transcription Translation Protein that stimulates cell division 103

104 11.18 Faulty proteins can interfere with normal signal transduction pathways
A second pathway produces a product that inhibits cell division. The normal product of the p53 gene is a transcription factor that normally activates genes for factors that inhibit cell division. In the absence of functional p53, cell division continues because the inhibitory protein is not produced. Mutations in p53 occur in more than 50% of human cancers. Teaching Tips Mutations in the ras or p53 genes are like having car problems in which the gas pedal overaccelerates or the brakes on the car fail to function. In either situation, an accident is more likely to occur. © 2012 Pearson Education, Inc. 104

105 Growth-inhibiting factor
Figure 11.18B Growth-inhibiting factor Receptor Relay proteins Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription Transcription factor (activated) Normal product of p53 gene Figure 11.18B An inhibitory signal transduction pathway and the effect of a faulty tumor-suppressor protein Transcription Translation Protein that inhibits cell division Protein absent (cell division not inhibited) 105

106 11.19 CONNECTION: Lifestyle choices can reduce the risk of cancer
After heart disease, cancer is the second-leading cause of death in most industrialized nations. Cancer can run in families if an individual inherits an oncogene or a mutant allele of a tumor-suppressor gene that makes cancer one step closer. But most cancers cannot be associated with an inherited mutation. Student Misconceptions and Concerns Many students do not appreciate the increased risk of skin cancer associated with the use of tanning beds, which is still popular with many college-age populations. Teaching Tips 1. 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. Furthermore, people may feel obliged or be obligated to share this information with a potential mate or employer. 2. 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 website for the American Cancer Society at © 2012 Pearson Education, Inc. 106

107 11.19 CONNECTION: Lifestyle choices can reduce the risk of cancer
Carcinogens are cancer-causing agents that alter DNA. Most mutagens (substances that promote mutations) are carcinogens. Two of the most potent carcinogens (mutagens) are X-rays and ultraviolet radiation in sunlight. Student Misconceptions and Concerns Many students do not appreciate the increased risk of skin cancer associated with the use of tanning beds, which is still popular with many college-age populations. Teaching Tips 1. 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. Furthermore, people may feel obliged or be obligated to share this information with a potential mate or employer. 2. 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 website for the American Cancer Society at © 2012 Pearson Education, Inc. 107

108 11.19 CONNECTION: Lifestyle choices can reduce the risk of cancer
The one substance known to cause more cases and types of cancer than any other single agent is tobacco. More people die of lung cancer than any other form of cancer. Although most tobacco-related cancers come from smoking, passive inhalation of second-hand smoke is also a risk. Tobacco use, sometimes in combination with alcohol consumption, causes cancers in addition to lung cancer. Student Misconceptions and Concerns Many students do not appreciate the increased risk of skin cancer associated with the use of tanning beds, which is still popular with many college-age populations. Teaching Tips 1. 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. Furthermore, people may feel obliged or be obligated to share this information with a potential mate or employer. 2. 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 website for the American Cancer Society at © 2012 Pearson Education, Inc. 108

109 11.19 CONNECTION: Lifestyle choices can reduce the risk of cancer
Healthy lifestyles that reduce the risks of cancer include avoiding carcinogens, including the sun and tobacco products, exercising adequately, regular medical checks for common types of cancer, and a healthy high-fiber, low-fat diet including plenty of fruits and vegetables. Student Misconceptions and Concerns Many students do not appreciate the increased risk of skin cancer associated with the use of tanning beds, which is still popular with many college-age populations. Teaching Tips 1. 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. Furthermore, people may feel obliged or be obligated to share this information with a potential mate or employer. 2. 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 website for the American Cancer Society at © 2012 Pearson Education, Inc. 109

110 Table 11.19 Table Cancer in the United States 110

111 Table 11.19_1 Table 11.19_1 Cancer in the United States (part 1) 111

112 Table 11.19_2 Table 11.19_2 Cancer in the United States (part 2) 112

113 You should now be able to
Describe and compare the regulatory mechanisms of the lac operon, trp operon, and operons using activators. Explain how selective gene expression yields a variety of cell types in multicellular eukaryotes. Explain how DNA is packaged into chromosomes. Explain how a cat’s tortoiseshell coat pattern is formed and why this pattern is only seen in female cats. © 2012 Pearson Education, Inc. 113

114 You should now be able to
Explain how eukaryotic gene expression is controlled. Describe the process and significance of alternative DNA splicing. Describe the significance of miRNA molecules. Explain how mRNA breakdown, initiation of translation, protein activation, and protein breakdown regulate gene expression. © 2012 Pearson Education, Inc. 114

115 You should now be able to
Describe the roles of homeotic genes in development. Explain how DNA microarrays can be used to study gene activity and treat disease. Explain how a signal transduction pathway triggers a specific response inside a target cell. Compare the cell-signaling systems of yeast and animal cells. © 2012 Pearson Education, Inc. 115

116 You should now be able to
Explain how nuclear transplantation can be used to clone animals. Describe some of the practical applications of reproductive cloning and the process and goals of therapeutic cloning. Explain how viruses, proto-oncogenes, and tumor-suppressor genes can each contribute to cancer. Explain why the development of most cancers is a slow and gradual process. © 2012 Pearson Education, Inc. 116

117 You should now be able to
Explain how mutations in ras or p53 proteins can lead to cancer. Describe factors that can increase or decrease the risks of developing cancer. © 2012 Pearson Education, Inc. 117

118 Encodes a repressor that in active form attaches to an operator
Figure 11.UN01 A typical operon Regulatory gene Promoter Operator Gene 1 Gene 2 Gene 3 DNA Encodes a repressor that in active form attaches to an operator RNA polymerase binding site Switches the operon on or off Code for proteins Figure 11.UN01 Reviewing the Concepts, 11.1 118

119 Egg cell or zygote with nucleus removed
Figure 11.UN02 Egg cell or zygote with nucleus removed An early embryo resulting from nuclear trans- plantation Surrogate mother Clone of the donor Nucleus from a donor cell Figure 11.UN02 Reviewing the Concepts, 11.13 119

120 Egg cell or zygote with nucleus removed
Figure 11.UN03 Egg cell or zygote with nucleus removed An early embryo resulting from nuclear trans- plantation Embryonic stem cells in culture Specialized cells Nucleus from a donor cell Figure 11.UN03 Reviewing the Concepts, 11.15 120

121 prokaryotic genes are often grouped into
Figure 11.UN04 Gene regulation (a) prokaryotic genes are often grouped into is a normal gene that can be mutated to an in eukaryotes may involve when abnormal may lead to operons oncogene controlled by a protein called can cause are switched on/off by (b) (c) in active form binds to Figure 11.UN04 Connecting the Concepts, question 1 (d) (e) (f) (g) are proteins that promote occurs in can produce female mammals multiple kinds of mRNA per gene transcription 121


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