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BIOLOGY 1A03
Cellular and Molecular Biology

Theme 3
Module 1 & 2 Review
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Module 1

Responding to the Environment

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Genes contain instructions
• Genes are made up of DNA

• Contain the instructions to make proteins

• Can vary in size from a few hundred DNA nucleotide bases to thousands

• The human genome project estimates humans have between 20,000-

25,000 genes that code for proteins (some coding for different versions of
the same protein!)
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Gene categories
• Housekeeping genes are constitutively
expressed (“ON” all the time)
• Includes: structural proteins,ribosomal
proteins etc.
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Gene categories
• Housekeeping genes are constitutively
expressed (“ON” all the time)
• Includes: structural proteins,ribosomal
proteins etc.

• Regulated genes are expressed only

when needed.
• Includes: enzymes
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Regulating gene expression
Transcriptional Control

X • Ability of RNA polymerase to bind to or transcribe a gene

Fastest?
Post-translational control
Last stage of gene expression
Translational Control (adding a phosphate or hydroxyl)

Slowest?
• Translation rates, lifetime of RNA
X Transcriptional control
Starting from scratch

Most Efficient?
Post-translational Control Transcriptional control
Doesn’t waste any energy until you need it

X • Post-translational modifications which may change folding and/or

activity
DNA contains the information needed to orchestrate a 7

response to any environmental change

Eg. When running out of nutrient resources in bacteria

What happens here?

Does the flat line
mean that the
bacterial cells have
died? How do you
interpret this?
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Changes in cell behaviour- The Glucose Effect
Most of our understanding of how gene regulation works in living
systems came from detailed studies with bacteria

Now, start the

experiment again,
but this time, we
place both glucose
(a monosaccharide)
and lactose (a Q: Why were the
disaccharide) in the bacteria not
beaker together metabolizing
with the bacteria… lactose from the
very start of the
experiment?
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Changes in protein production
DNA contains the information needed to orchestrate a
response to any environmental change

The ability of bacteria

to metabolize lactose,
is dependent on the
expression of a cluster
of genes that are
regulated together
(see here rate of
production for one
enzyme that is coded
for in the gene cluster)
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The cell can metabolize lactose

Lactose turns on the gene that produces β-Galactosidase

(Lactose is an “inducer”)
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Module 2

Prokaryotic Transcriptional Regulation

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Transcriptional responses to the environment
Control of enzyme production for lactose metabolism is regulated at transcriptional level
This lag phase, is the
period when the
expression of beta-
galactosidase and
lactose permease is
being induced

…these are regulated

genes that are turned on
mostly during periods of
low glucose and high
lactose availability
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Transcriptional responses to the environment
Control of enzyme production for lactose metabolism is regulated at transcriptional level

Cues:
-decrease in
glucose levels
-availability of
lactose in the
environment

BUT HOW?
 Bacterial genes with related functions are 14

clustered into operons

Genes within an
operon are
regulated by ONE
single promoter and
are expressed at the
same time

This is very different

from our own
eukaryotic genes…
lac operon encodes a polycistronic mRNA.
• This is an mRNA molecule that contains more than one protein encoding segment
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Cues lead to gene expression products
Expression of lactose permease protein and β-Galactosidase is linked based
on their functional relatedness
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Negative Regulation of the Lac Operon

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The lactose operon is negatively regulated

Normally kept in a
MOSTLY off state in the
presence of glucose….
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Lactose is an inducer of transcription

Lactose removes
negative regulation of
lac operon
…so lactose is an
inducer of this operon
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The lactose operon is negatively regulated
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Lactose induces lac operon gene expression
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Positive Regulation of the Lac Operon

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Glucose regulates adenylyl cyclase activity
GLUCOSE INHIBITS positive regulation is influenced by
THIS ENZYME glucose levels, and involves a
signaling molecule in the cell called
cyclic AMP (cAMP)

• cAMP is synthesized from ATP adenylyl cyclase

Therefore:
LOW when glucose levels are high.
• cAMP levels will be________
HIGH when glucose levels are low.
• cAMP levels will be _________
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cAMP signals the nutritional state of E.coli cells

Together with the

presence of lactose in
the environment, this
CRP-cyclic AMP
complex facilitates
the ability of RNA
polymerase to bind to
the lac promoter
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cAMP signals the nutritional state of E.coli cells

In contrast, we don’t
see this level of positive
regulation of the lac
operon when glucose
levels are high

Overall: We now know that the lac operon is positively regulated in low glucose
environments, but is normally negatively regulated in high glucose environments.
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The lactose paradox- is the lac operon ever fully OFF?
Is operon expression completely off in the presence of ONLY glucose? How does lactose
get into the cell???
Challenges:
• Lactose can’t enter the cell (to inhibit the repressor protein) unless it is transported
across the membrane
• Permease is only in the membrane if lac operon is “ON”
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of operon expression

The lac operon is never fully off!

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Tomorrow’s applied lecture…

Treating lactose intolerance