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Transcript
Control, Genomes and
Environment
Cellular Control – homeobox genes and
apoptosis
Learning Outcomes
• explain that the genes that control development of
body plans are similar in plants, animals and
fungi, with reference to homeobox sequences
(HSW1)
• outline how apoptosis (programmed cell death)
can act as a mechanism to change body plans
Controlling development
All organisms begin life as a single
cell. This cell divides and the new
cells produced start to differentiate
and specialize.
‘Switching on’ the expression of a
gene or keeping it switched off
determines the development of
features.
Many organisms contain similar genes that control development of
body plans. For example groups of genes called the homeobox
genes play an important role in the development of many
multicellular organisms.
Homeobox genes
• Homeobox genes determine how an organism’s
body develops as it grows from a zygote into a
complete organism.
• They determine the organism’s body plan
• These sequences are highly conserved, which
implies that their activity is fundamental to the
development of an organism
• Homeobox genes have been discovered in animals,
plants and fungi
Homeobox genes
The genome of the fruit fly contains one ‘set’ or cluster of
homeobox genes. These control development, including the
polarity of the embryo, polarity of each segment and the identity
of each segment.
Homeobox genes code for
transcriptional factors. These
regulate the expression of other
genes important in development.
Mutations in homeobox genes can cause changes in the body
plan. For example a mutation in the gene controlling leg
placement can cause legs to grow where the antennae are
normally found.
Homeobox genes
Homeobox genes are present in the
genomes of most organisms. They
control development of body parts in
similar ways.
There is little variation in many
regions of the homeobox genes in
different organisms. This suggests
that these have been highly
conserved throughout evolutionary
history. They are thought to be
especially important to the basic
development of organisms.
Homologous homeobox genes
• These are the sequences of 60 amino acids in the
proteins coded for by the homeobox genes Antp in a fruit
fly and HoxB7 in a mouse.
• All animals have homologous homeobox genes – they
are recognisably similar
What do homeobox genes do?
• Homeobox genes code for the production of
transcription factors (homeodomain)
• These proteins can bind to a particular region of
DNA and activate or repress the gene
– A single homeobox gene can switch on a whole
collection of other genes, regulating gene expression
• This allows the correct development of the body
plan.
Genes and Body plans
• Drosophila melanogaster a.k.a. fruit fly
• Body is divided into
– Head
– Thorax
– abdomen
Genetic control of Drosophila
development
• Development is mediated by homeobox
genes
– Maternal effect genes determine the embryo’s
polarity e.g. anterior (head) & posterior (tail /
abdomen)
– Segmentation genes determine polarity of each
segment
– Homeotic selector genes identify and direct the
development of each segment
• Two groups exist, that control development of (i) head
+ thorax segments and (ii) thorax + abdomen
segments.
Drosophila thorax
• The Thorax of the fruit fly is split into 3 segments
– T1 – a pair of legs
– T2 – a pair of legs and a pair of wings
– T3 – a pair of legs and a pair of halteres
Ubx in fruit fly
• A homeobox gene
called Ubx stops the
formation of wings in
T3.
• A mutation in both
copies of Ubx, wings
grow in T3 instead of
halteres.
Ubx
Mutant
Ubx
Antp in fruit fly
• If the homeobox gene
Antp is usually turned on
in the thorax, where it
causes legs to develop.
• In mutant flies where Antp
is switched on in the
head, legs grow instead
of antennae
Hox Clusters
• Hox clusters are aggregations of homeobox
genes and are found in all animals.
• Examples
• Nematodes have one Hox cluster
• Fruit flies have 2 Hox clusters
• Vertebrates have 4 Hox clusters
Read p114-5 in purple book
• Add any information to your notes made on
homeobox genes and answer q on p115.
• Include the first example of the interference of
homeobox functioning in humans.
Homeobox genes in humans
• Effect of thalidomide in embryo development
– Homeobox genes HoxA11 and HoxD11 switch on
genes that cause forelimb development.
– The drug thalidomide affected the behaviour of these
homeobox genes at a critical stage in embryonic
development.
Apoptosis – programmed cell death
• Cell death as part of normal
development
• Happens in stages
• Complete the sheet Apoptosis:
• programmed cell death.
• Ensure you are clear about the stages
and the example of syndactyly
• Purple book 116-7, Green book p105 to help.
Plenary
• Suggest how one gene may inhibit the action of
another. (3 marks)
•
•
•
•
•
•
codes for inhibitor;
protein;
blocks transcription (of allele coding for pigment);
ref to, regulator / promoter;
blocks enzyme (producing pigment);
AVP; e.g. detail
Spec Check
Homework
• Read the scientific article (start of) which will give
you more detail about the potential role of
apoptosis in cancer treatment.
• Find out about siRNA
Learning Outcomes
• explain that the genes that control development of
body plans are similar in plants, animals and
fungi, with reference to homeobox sequences
(HSW1)
• outline how apoptosis (programmed cell death)
can act as a mechanism to change body plans
Control, Genomes and
Environment
Cellular Control – Translational control siRNA
Translational control
• Small interfering RNA (siRNA) are short
pieces of double-stranded RNA that
interferes with the expression of a specific
gene.
• The siRNA is complementary to the mRNA
produced during transcription.
• It binds to the mRNA, it is chopped into pieces
and cannot combine with the ribosome.
• Thus it cannot be translated.
siRNA inhibits translation of mRNA and turns
genes OFF
siRNA
unwinds.
Now single
stranded
Complementary
base pairing
between siRNA
and target
mRNA
Enzyme 1
breaks up
dsRNA
making
siRNA
molecules
Enzyme 2 cuts
mRNA into
small sections
stopping it from
being translated
Exam Practice
• Q7, Q8, Q14 in mrsmillers F215 document
Answers
• Q7 (a)
(i)
mRNA leaves nucleus; ora
mRNA, translated / used to make, protein;
DNA, transcribed / used to make, mRNA;
mRNA short-term / DNA (long-term) store; 2 max
• (ii) siRNA smaller / fewer nucleotides / only
matches part of gene; ora
siRNA double-stranded; ora 2
Answers
• Q8 (b)
(complementary) base-pairing;
hydrogen bonding;
between purines and pyrimidines;
A with U; R A with T
C with G;
ref to 2 or 3 bonds (correct context); 3 max
• 8. (i)
(CCR5 / macrophages)
(siRNAs continue to work) in long-lived cells;
only one treatment needed for macrophages /
CCR5;
(siRNAs diluted) as lymphocytes divide; ora
repeat treatments needed for, lymphocytes / CD4; 2
• (ii) (CCR5)
because no essential function in body / absence not
a problem; 1
Answers
•
•
•
•
•
•
•
•
•
•
14. (i)
RNA(i) combines with mRNA;
e.g. of base pairing (but not T) A-U / G-C;
stops translation;
ref to stops mRNA combining with ribosomes;
stops protein synthesis;
max 3
(ii) chemicals / enzymes in, mouth / toothpaste /
bacteria;
denature / degrade, RNA;
RNA not normally taken up by bacterial cells;
short life of RNA;
RNA not replicated in bacteria when bacteria
reproduce;
Answers
• (ii) chemicals / enzymes in, mouth / toothpaste /
bacteria;
• denature / degrade, RNA;
• RNA not normally taken up by bacterial cells;
• short life of RNA;
• RNA not replicated in bacteria when bacteria
reproduce;
• toothpaste in mouth only for short time;
• AVP;
• AVP;
e.g. washed away by saliva
max 2