Download Gene expression

Chapter 11
How Genes Are Controlled
PowerPoint Lectures for
Campbell Biology: Concepts & Connections, Seventh Edition
Reece, Taylor, Simon, and Dickey
© 2012 Pearson Education, Inc.
Lecture by Edward J. Zalisko
Figure 11.0_1
Chapter 11: Big Ideas
Control of Gene
Expression
The Genetic Basis
of Cancer
Cloning of Plants
and Animals
CONTROL OF GENE
EXPRESSION
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Gene expression is the overall process of
information flow from genes to proteins.
 Gene regulation is the turning on and off of genes.
 Why is that gene expression has to be regulated?
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 The control of gene expression allows cells to
produce specific kinds of proteins when and where
they are needed.
 Gene regulation can help organism respond to
environmental changes
 Skip the lac operon
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11.2 Chromosome structure and chemical
modifications can affect gene expression
Differentiation
 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.
 Humans have about 25,000 genes and only a fraction of
these genes are used or expressed in each cell involves
cell specialization, in structure and function, and
 Differentiation is controlled by turning specific sets of
genes on or off.
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Some types of human cells. All cells have the same DNA
Muscle cell
Pancreas cells
Blood cells
11.2 Chromosome structure and chemical
modifications can affect gene expression
How gene expression is regulated
 DNA packing
 Epigenetic modifications
 X chromosome inactivation
 Control of gene expression by RNA (11.5)
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11.2 Chromosome structure and chemical
modifications can affect gene expression
DNA packing
 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.
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Figure 11.2A
DNA packing in a eukaryotic chromosome
DNA double helix
(2-nm diameter)
Metaphase
chromosome
Nucleosome
(10-nm diameter)
Linker
“Beads on
a string”
Histones Supercoil
(300-nm diameter)
Tight helical
fiber (30-nm
diameter)
700 nm
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 longterm inactivation of genes.
 Highly compacted chromatin, found in varying regions
of interphase chromosomes, is generally not
expressed at all.
© 2012 Pearson Education, Inc.
11.2 Chromosome structure and chemical
modifications can affect gene expression
Epigenetic modifications
 Chemical modification of DNA bases
 And modification of histone proteins
 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.
© 2012 Pearson Education, Inc.
11.2 Chromosome structure and chemical
modifications can affect gene expression
Epigenetic modifications
 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.
 Potential for drug development based on epigenetics
 More from the video “Ghost in your genes”
© 2012 Pearson Education, Inc.
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.
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Figure 11.2B
A tortoiseshell pattern on a female cat, a result of
X chromosome inactivation
Early Embryo
Adult
Two cell populations
X chromosomes
Allele for
orange fur
Cell division
and random
X chromosome Active X
inactivation Inactive X
Allele for
black fur
Inactive X
Active X
Orange
fur
Black fur
11.5 Small RNAs play multiple roles in controlling
gene expression
Small RNAs control 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 DNA 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.
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Figure 11.5
Protein
miRNA
1
RNA interference
miRNAprotein
complex
2
Target mRNA
3
or
4
Translation
blocked
mRNA degraded
11.5 Small RNAs play multiple roles in
controlling gene expression
 Question: If a gene has a sequence of
AATTCGCG, design an miRNA piece that can
inactivate the gene
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THE GENETIC BASIS
OF CANCER
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11.16 Cancer results from mutations in genes
that control cell division
Cancer is a disease of damaged DNA
 Every time a cell divides, it must accurately copy its
DNA. It is estimated that 100 million million cell
divisions take place during an average human life
time.
 Every cell has the potential to introduce a mutation
(an error) into a daughter cell
 Although many mutations are harmless, when
mutation takes place in a critical gene, the normal
cell can be turned into a cancerous cell.
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11.16 Cancer results from mutations in genes
that control cell division
Mutations in two types of genes can lead to
cancer
1. Proto-oncogenes
2. Tumor suppresor genes
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11.16 Cancer results from mutations in genes
that control cell division
Oncogenes
 Proto-oncogenes are normal genes that stimulate
cell division.
 Mutations in proto-oncogenes can turn them into
cancer-causing oncogenes
 A cell can acquire an oncogene from a mutated
proto-oncogene or from viruses, eg: cervical
cancer
 A gene called ras is a proto-oncogene. Mutations
in ras occur in more than 30% of human cancers.
© 2012 Pearson Education, Inc.
Figure 11.16A
Proto-oncogene
(for a protein that stimulates cell division)
DNA
A mutation within
the gene
Multiple copies
of the gene
Oncogene
Hyperactive
growthstimulating
protein in a
normal amount
The gene is moved to
a new DNA locus,
under new controls
New promoter
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
11.16 Cancer results from mutations in genes
that control 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.
 Eg: p53 is tumor suppressor gene mutated in
almost a half of all human cancers
 Mutations in BRCA1 and BRCA2 can lead to
breast cancer
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Figure 11.16B
Tumor-suppressor gene
Normal
growthinhibiting
protein
Cell division
under control
Mutated tumor-suppressor gene
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 turn a normal cell into a full-fledged cancer cell.
 One possible scenario is the stepwise development of
colorectal cancer.
1. An oncogene 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.
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Figure 11.17B
Accumulation of mutations in the development
of a cancer cell
1
Chromosomes mutation
Normal
cell
2
mutations
3
4
mutations mutations
Malignant
cell
Figure 11.17A
Stepwise development of a typical colon cancer
An oncogene A tumor-suppressor
DNA
changes: is activated gene is inactivated
A second tumorsuppressor gene
is inactivated
Cellular
Increased
changes: cell division
1
Growth of a
malignant tumor
3
Colon wall
Growth of a polyp
2
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 is not one disease, but a group of more than
200 (see table 11.19 for a partial list)
 All cancers are ultimately diseases of our genes
 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.
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Table 11.19
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.
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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.
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11.19 CONNECTION: Lifestyle choices can
reduce the risk of cancer
 Healthy lifestyles that reduce the risks of cancer
include
– avoiding carcinogens, including chemicals, the sun and
tanning beds
– avoiding 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.
© 2012 Pearson Education, Inc.