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Controls Over Genes
Chapter 15
Impacts, Issues:
Between You and Eternity
 Mutations in some genes predispose individuals
to develop certain kinds of cancer; mutations in
BRAC genes cause breast cancer
normal cells in
organized clusters
irregular clusters
of malignant cells
Fig. 15-1b, p. 228
15.1 Gene Expression in Eukaryotic Cells
 Gene controls govern the kinds and amounts of
substances in a cell at any given interval
 Various control processes regulate all steps
between gene and gene product
Which Genes Get Tapped?
 Differentiation
• The process by which cells become specialized
• In multicelled organisms, most cells differentiate
when they start expressing a unique subset of
their genes
• Which genes are expressed depends on the type
of organism, its stage of development, and
environmental conditions
Control of Transcription
 Transcription factors
• Regulatory proteins that affect the rate of
transcription by binding to special nucleotide
sequences in DNA
• Activators speed up transcription when bound to
a promoter; or may bind to distant enhancers
• Repressors slow or stop transcription
Promoter and Enhancers
enhancer
promoter
exon1
intron exon2
transcription start site
enhancer
transcription end
Fig. 15-3, pp. 230-231
Control of Transcription
 Chemical modifications and chromosome
duplications affect RNA polymerase’s access to
genes
• Interactions between DNA and histone proteins
(methylation) prevent transcription
• Polytene chromosomes (many copies) increase
transcription rates in some organisms
Drosophila Polytene Chromosomes
Controls of mRNA Transcripts
 mRNA processing
• DNA splicing controls products of translation
 mRNA transport controls delivery of transcripts
• Passage through nuclear pores
• Delivery within cytoplasm (mRNA localization)
Translational Controls
 Controls over molecules involved in translation
 Controls over mRNA stability
• Depends on base sequence, length of poly-A tail,
and which proteins are attached to it
 RNA interference
• Expression of a microRNA complementary to a
gene inhibits expression of the gene
Post-Translational Modification
 Post-translational modification can inhibit,
activate, or stabilize many molecules, including
enzymes that participate in transcription and
translocation
Points of Control over
Eukaryotic Gene Expression
DNA
NUCLEUS
A Transcription
Binding of transcription factors to special sequences in DNA slows or
speeds transcription. Chemical modifications and chromosome
duplications affect RNA polymerase’s physical access to genes.
new RNA
transcript
B mRNA Processing
New mRNA cannot leave the nucleus before being modified, so controls
over mRNA processing affect the timing of transcription. Controls over
alternative splicing influence the final form of the protein.
mRNA
C mRNA Transport
RNA cannot pass through a nuclear pore unless bound to certain
proteins. Transport protein binding affects where the transcript will be
delivered in the cell.
CYTOPLASM
mRNA
D Translation
An mRNA’s stability influences how long it is translated. Proteins that
attach to ribosomes or initiation factors can inhibit translation. Doublestranded RNA triggers degradation of complementary mRNA.
polypeptide
chain
active
protein
E Protein Processing
A new protein molecule may become activated or disabled by enzymemediated modifications, such as phosphorylation or cleavage. Controls
over these enzymes influence many other cell activities.
Stepped Art
Fig. 15-2, p. 230
Animation: Controls of eukaryotic gene
expression
15.1 Key Concepts: Overview of
Controls Over Gene Expression
 A variety of molecules and processes alter gene
expression in response to changing conditions
both inside and outside the cell
 Selective gene expression also results in cell
differentiation, by which different cell lineages
become specialized
15.2 A Few Outcomes
of Eukaryotic Gene Controls
 Selective gene expression can give rise to
visible traits
X Chromosome Inactivation
 X chromosome inactivation
• In cells of female mammals, either the maternal
or paternal X chromosome is randomly
condensed (Barr body) and is inactive
• Occurs in an early embryonic stage, so that all
descendents of that particular cell have the same
inactive X chromosome, resulting in “mosaic”
gene expression
X Chromosome Inactivation
Fig. 15-5a, p. 232
Fig. 15-5b, p. 232
Fig. 15-5c, p. 232
Calico: Mosaic Gene Expression
in a Female Mammal
Animation: X-chromosome inactivation
Dosage Compensation
 Dosage compensation
• The theory that X chromosome inactivation
equalizes expression of X chromosome genes
between the sexes
 Mechanism of X inactivation
• XIST gene on one X chromosome transcribes an
RNA molecule which coats the chromosome and
causes it to condense, forming a Barr body
Flower Formation
 The ABC model
• Three sets of master genes (A,B,C) encode
products that initiate cascades of expression of
other genes to accomplish intricate tasks such as
flower formation
• Master genes are expressed differently in tissues
of floral shoots
• Master genes are switched on by environmental
cues such as day length
Controls of Flower Formation
Fig. 15-7a, p. 233
petals
carpel
sepals stamens
A The pattern in which the floral
identity genes A, B, and C are
expressed affects differentiation
of cells growing in whorls in the
plant’s tips. Their gene products
guide expression of other genes
in cells of each whorl; a flower
results.
Fig. 15-7a, p. 233
Fig. 15-7b, p. 233
Animation: ABC model for flowering
15.2 Key Concepts
Examples From Eukaryotes
 The orderly, localized expression of certain
genes in embryos gives rise to the body plan of
complex multicelled organisms
 In female mammals, most of the genes on one
of the two X chromosomes are inactivated in
every cell
15.3 There’s a Fly in My Research
 Many important discoveries have resulted from
studies of the fruit fly, Drosophila melanogaster
 Research with fruit flies yielded the insight that
body plans are a result of patterns of gene
expression in embryos
Discovery of Homeotic Genes
 Homeotic genes
• Master genes that control differentiation of
specific tissues and body parts in an embryo
• Encode transcription factors with a homeodomain
 Homeodomain
• A region of about 60 amino acids that can bind to
a promoter or some other sequence in DNA
Homeotic Gene Experiments
 Antennapedia
Fig. 15-8a, p. 234
Fig. 15-8b, p. 234
Fig. 15-8c, p. 234
Fig. 15-8de, p. 235
Fig. 15-8d, p. 235
Fig. 15-8e, p. 235
Knockout Experiments
 Knockout experiments
• Researchers inactivate a gene by introducing a
mutation into it, then compare the differences with
normal individuals – and similar genes in humans
• Example: The PAX6 gene in humans is a
homologue of the eyeless gene in Drosophila
Filling in Details of Body Plans
 Pattern formation
• As an embryo develops, cells that differentiate in
different body regions migrate and form tissues,
creating complex body forms from local
processes driven by master genes
• Regional gene expression during development
results in a 3-dimesional map that consists of
overlapping concentrations of master gene
products, which change over time
Gene Expression and Pattern Formation
Fig. 15-9a, p. 235
Fig. 15-9b, p. 235
Fig. 15-9c, p. 235
Fig. 15-9d, p. 235
Fig. 15-9e, p. 235
Fig. 15-9f, p. 235
15.3 Key Concepts
Fruit Fly Development
 Drosophila research revealed how a complex
body plan emerges
 All cells in a developing embryo inherit the same
genes, but they activate and suppress different
fractions of those genes
15.4 Prokaryotic Gene Control
 Prokaryotes are single celled and do not have
master genes
 Prokaryotes control gene expression mainly by
adjusting the rate of transcription in response to
shifts in nutrient availability and other outside
conditions
Prokaryotic Gene Control
 In prokaryotes, genes that are used together
often occur together on chromosomes
 Operon
• A promoter and one or more operators that
collectively control transcription of multiple genes
 Operators
• DNA regions that are binding sites for a repressor
The Lactose Operon
 E. coli digest lactose in guts of mammals using a
set of three enzymes controlled by two operators
and a single promoter (the lac operon)
• When lactose is not present, repressors bind to
the operators and inactivate the promoter;
transcription does not proceed
• When lactose is present, allolactose binds to the
repressors; repressors don’t bind to operators to
inactivate the promoter; transcription proceeds
The Lactose Operon Repressor
repressor
looped-up
DNA
looped-up
DNA
Fig. 15-10, p. 236
The Lactose Operon
Lactose absent
Lactose Operon
operator promoter operator
Repressor protein
Lactose present
lactose
gene 1
gene 2
gene 3
A The lac operon in the E. coli chromosome.
B In the absence of lactose, a repressor binds to the two
operators. Binding prevents RNA polymerase from attaching to the
promoter, so transcription of the operon genes does not occur.
gene 2
gene 3
gene 1
C When lactose is present, some is converted to a form
that binds to the repressor. Binding alters the shape of
the repressor such that it releases the operators. RNA
polymerase can now attach to the promoter and
transcribe the operon genes.
RNA polymerase
mRNA
operator promoter operator
gene 1
gene 2
gene 3
Fig. 15-11, p. 237
Lactose absent
Lactose Operon
operator promoter operator
Repressor protein
Lactose present
lactose
gene 1
gene 2
gene 3
A The lac operon in the E. coli chromosome.
B In the absence of lactose, a repressor binds to the two
operators. Binding prevents RNA polymerase from attaching to the
promoter, so transcription of the operon genes does not occur.
gene 2
gene 3
gene 1
C When lactose is present, some is converted to a form
that binds to the repressor. Binding alters the shape of
the repressor such that it releases the operators. RNA
polymerase can now attach to the promoter and
transcribe the operon genes.
RNA polymerase
mRNA
operator promoter operator
gene 1
gene 2
gene 3
Stepped Art
Fig. 15-11, p. 237
Animation: The lactose operon
Animation: Negative control of the
lactose operon
Lactose Intolerance
 Human infants and other mammals produce the
enzyme lactase, which digests the lactose in
milk – adults tend to lose the ability to produce
lactase, and become lactose intolerant
15.4 Key Concepts
Examples From Prokaryotes
 Prokaryotic gene controls govern responses to
short-term changes in nutrient availability and
other aspects of the environment
 The main gene controls bring about fast
adjustments in the rate of transcription
Animation: Fate map
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Video: Between you and eternity