Chapter 11 How Genes Are Controlled Introductioniws.collin.edu/atassa/course-files/Biol_1408_Ch_11_6_Slide.pdf© 2012 Pearson Education, Inc. Lecture by Edward J. Zalisko PowerPoint

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© 2012 Pearson Education, Inc. Lecture by Edward J. Zalisko

PowerPoint Lectures for Campbell Biology: Concepts & Connections, Seventh Edition Reece, Taylor, Simon, and Dickey

Chapter 11 How Genes Are Controlled

  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.

Introduction

© 2012 Pearson Education, Inc.

  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.

Introduction


Figure 11.0_1 Chapter 11: Big Ideas

Control of Gene Expression

Cloning of Plants and Animals

The Genetic Basis of Cancer

CONTROL OF GENE EXPRESSION


  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.

11.1 Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes


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Figure 11.1A

E. coli


  A cluster of genes with related functions, along with the control sequences, is called an operon.

  With few exceptions, operons only exist in prokaryotes.



  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

1.  three adjacent lactose-utilization genes,

2.  a promoter sequence where RNA polymerase binds and initiates transcription of all three lactose genes, and

3.  an operator sequence where a repressor can bind and block RNA polymerase action.



  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.


Figure 11.1B

Operon turned off (lactose is absent): OPERON

Regulatory gene

Promoter Operator Lactose-utilization genes

RNA polymerase cannot attach to the promoter

Active repressor

Protein

mRNA

DNA

Protein

mRNA

DNA

Operon turned on (lactose inactivates the repressor):

RNA polymerase is bound to the promoter

Lactose Inactive repressor

Translation

Enzymes for lactose utilization


  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).


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Figure 11.1C

Inactive repressor

Inactive repressor

Active repressor

Active repressor

Lactose

Tryptophan

DNA Promoter Operator Gene

lac operon trp operon


  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.


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.



  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.



  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.



  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.


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–  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.



  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.


Figure 11.2A

DNA double helix (2-nm diameter)

“Beads on a string”

Linker

Histones Supercoil (300-nm diameter)

Nucleosome (10-nm diameter)

Tight helical fiber (30-nm diameter)

Metaphase chromosome

700 nm

Figure 11.2B

Cell division and random

X chromosome inactivation

Early Embryo Adult

X chromosomes

Allele for orange fur

Allele for black fur

Two cell populations

Active X Inactive X

Active X Inactive X

Black fur

Orange fur

Figure 11.2B_1

Cell division and random

X chromosome inactivation

Early Embryo Adult

X chromosomes

Allele for orange fur

Allele for black fur

Two cell populations

Active X Inactive X

Active X Inactive X

Black fur

Orange fur

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.


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  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.


Figure 11.3 Enhancers

DNA

Promoter Gene

Transcription factors

Activator proteins

Other proteins

RNA polymerase

Bending of DNA

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.


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.


Figure 11.4

DNA

RNA transcript

mRNA

Exons

Introns Introns

Cap Tail

RNA splicing

or

1

1

1 1

2

2

2 2

4

4

4

5

5

5 5

3

3

3

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.


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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.


Figure 11.5

miRNA

Target mRNA

mRNA degraded

or

Translation blocked

miRNA- protein complex

Protein

3

2

1

4

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.


Figure 11.6

Folding of the polypeptide and the formation of S—S linkages

Initial polypeptide (inactive)

Folded polypeptide (inactive)

Active form of insulin

Cleavage

S S

S S

S

S S

S

S S S S

SH SH

SH SH

SH

SH

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.

© 2012 Pearson Education, Inc. Animation: Protein Processing

Animation: Protein Degradation

Figure 11.7_1

Chromosome Chromosome

DNA unpacking Other changes to the DNA

Gene DNA

Transcription Gene

Exon

Intron

Tail

Cap

Addition of a cap and tail

RNA transcript

Splicing

mRNA in nucleus

NUCLEUS Flow through nuclear envelope

CYTOPLASM

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Figure 11.7_2

mRNA in cytoplasm CYTOPLASM

Breakdown of mRNA

Translation

Polypeptide Polypeptide

Broken- down mRNA

Cleavage, modification, activation

Active protein Active protein

Amino acids

Breakdown of protein


  These controls points include: 1.  chromosome changes and DNA unpacking,

2.  control of transcription,

3.  control of RNA processing including the –  addition of a cap and tail and

–  splicing,

4.  flow through the nuclear envelope,

5.  breakdown of mRNA,



6.  control of translation, and

7.  control after translation including –  cleavage/modification/activation of proteins and

–  breakdown of protein.


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.

1.  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.


11.8 Cell signaling and cascades of gene expression direct animal development

2. Segmentation of the body is influenced by cascades of proteins that diffuse through the cell layers.

3. Adult features develop under the influence of homeotic genes, master control genes that determine the anatomy of the parts of the body.


Figure 11.8A

Antenna

Eye

Extra pair of legs

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Figure 11.8B Egg cell within ovarian follicle

Follicle cells

“Head” mRNA

Embryo

Adult fly

Expression of homeotic genes and cascades of gene expression

Body segments

Fertilization and mitosis

Cascades of gene expression

Gene expression Growth of egg cell Localization of “head” mRNA

Egg cell

Egg cell

Egg cell and follicle cells signaling each other

2

1

3

4

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.


Figure 11.9

3

4

2

1 mRNA is isolated.

Reverse transcriptase and fluorescent DNA nucleotides

cDNA is made from mRNA.

Unbound cDNA is rinsed away.

cDNA is applied to the wells.

DNA microarray

Each well contains DNA from a particular gene.

Fluorescent spot

Nonfluorescent spot

cDNA

DNA of an expressed gene

DNA of an unexpressed gene

Actual size (6,400 genes)

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.


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.

© 2012 Pearson Education, Inc. Animation: Signal Transduction Pathways

Animation: Overview of Cell Signaling

Figure 11.10

3

2

1

4

5

6

Signaling cell EXTRACELLULAR FLUID Signaling molecule

Receptor protein

Plasma membrane

Target cell

Relay proteins

Signal transduction pathway

Transcription factor (activated)

NUCLEUS

DNA

mRNA

CYTOPLASM

Transcription

Translation

New protein

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Figure 11.10_1

3

2

1

Signaling cell EXTRACELLULAR FLUID Signaling molecule

Receptor protein

Plasma membrane

Target cell

Relay proteins

Signal transduction pathway

Figure 11.10_2

4

5

6


NUCLEUS

DNA

mRNA

CYTOPLASM

Transcription

Translation

New protein

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.


11.11 EVOLUTION CONNECTION: Cell-signaling systems appeared early in the evolution of life

  Yeast have two mating types: a and α. –  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.


Figure 11.11

Receptor

Yeast cell, mating type a

Yeast cell, mating type α

α factor

a factor

a

a

a/α

α

α CLONING OF PLANTS AND ANIMALS


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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.


Figure 11.12

Root of carrot plant

Root cells cultured in growth medium

Cell division in culture

Single cell

Plantlet Adult plant

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.


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.


Figure 11.13

The nucleus is removed from an egg cell.

Donor cell

A somatic cell from an adult donor is added.

Nucleus from the donor cell

Reproductive cloning

Blastocyst The blastocyst is implanted in a surrogate mother.

A clone of the donor is born.

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.

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.


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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.


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.


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.


Figure 11.15

Blood cells

Nerve cells

Heart muscle cells Different types of differentiated cells

Different culture conditions

Cultured embryonic stem cells

Adult stem cells in bone

marrow

THE GENETIC BASIS OF CANCER


11.16 Cancer results from mutations in genes that control cell division

  Mutations in two types of genes can cause cancer. 1.  Oncogenes

–  Proto-oncogenes are normal genes that promote cell division.

–  Mutations to proto-oncogenes create cancer-causing oncogenes that often stimulate cell division.

2.  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.


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Figure 11.16A

Oncogene

Hyperactive growth- stimulating protein in a normal amount

Normal growth- stimulating protein in excess

Normal growth- stimulating protein in excess

New promoter

The gene is moved to a new DNA locus,

under new controls

Multiple copies of the gene

A mutation within the gene

Proto-oncogene (for a protein that stimulates cell division)

DNA

Figure 11.16B

Tumor-suppressor gene Mutated tumor-suppressor gene

Normal growth- inhibiting protein

Cell division under control

Defective, nonfunctioning protein

Cell division not under control

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. 1.  An oncogene arises or is activated, resulting in

increased cell division in apparently normal cells in the colon lining.

2.  Additional DNA mutations cause the growth of a small benign tumor (polyp) in the colon wall.

3.  Additional mutations lead to a malignant tumor with the potential to metastasize.


Figure 11.17A

Colon wall

DNA changes:

Cellular changes:

Growth of a polyp

An oncogene is activated

Increased cell division

A tumor-suppressor gene is inactivated

A second tumor- suppressor gene

is inactivated Growth of a

malignant tumor 1 2 3

Figure 11.17B

Chromosomes 1

mutation 2

mutations 3

mutations 4

mutations

Normal cell

Malignant cell

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.


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1.  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.


Figure 11.18A Growth factor

Target cell

Normal product of ras gene Relay proteins

Receptor

Hyperactive relay protein (product of ras oncogene) issues signals on its own

CYTOPLASM

DNA

NUCLEUS Transcription

Translation Protein that stimulates cell division

Transcription factor

(activated)


2.  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.


Figure 11.18B Growth-inhibiting factor

Receptor

Relay proteins


Nonfunctional transcription factor (product of faulty p53 tumor-suppressor gene) cannot trigger transcription

Normal product of p53 gene

Transcription

Translation Protein that inhibits cell division

Protein absent (cell division not inhibited)

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.



  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.


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  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.



  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.


Table 11.19

Documents

Chapter 11 How Genes Are Controlled Introductioniws.collin.edu/atassa/course-files/Biol_1408_Ch_11_6_Slide.pdf© 2012 Pearson Education, Inc. Lecture by Edward J. Zalisko PowerPoint