Transcript Homeobox genes

Fly mutants
Normal fly
Extra set of wings!
Ubx (Ultrabithorax) gene mutant
Antennae are transformed into legs!
Antp (Antennapedia) gene mutant
Carroll S.B. et al. From DNA to Diversity (2001) Blackwell Science
What caused those body
parts to be in the
WRONG places?
What causes body parts to grow in the
CORRECT places?
Remember that
EVERY CELL of your body has ALL your GENEs
Homeosis
• Mutation that causes transformation of an
area of the body into another area
• The mutated genes:
– the so-called Homeobox genes
On your worksheet
• Choose 4 colours and assign a colour each to a, g and i
• Locate the regions labelled a, g and i in the diagrams of
the Drosophila Hox gene, the embryo and the adult
• Use your colour key to colour in these sections in the
Drosophila Hox gene, the embryo and the adult
What do you notice?
The pattern of Homeobox expression
Colinearity between the
order of the homeobox
genes and the expression
pattern
Adult
Eight homeobox genes
regulate the identity of
regions within the adult
and embryo.
The order of the genes
determines the body plan
Embryo
Carroll S.B. et al. From DNA to Diversity (2001) Blackwell Science
Homeobox genes
• All contain a 180 bp conserved region (does not change):
– the homeobox
– Transcription regulators which encode the protein sequences
above for (remember, the I gene which produces the lac operon
repressor is also a transcription regulator)
Homeodomain proteins
• Homeodomain proteins
– 60 aa long
– transcription factors
• DNA-binding proteins
• (remember that the repressor protein in the lac operon is also a transcription
regulator)
•
Binding of the homeodomain proteins to DNA
– Switches transcription on or off
– Determines body plans
Homeodomain bound to DNA
Types of Homebox genes
• Maternal effect
– Determines polarity:
• Anterior (head) and posterior (tail)
• Segmentation
– Specifies polarity of each segment
• Homeotic selector genes
– Master switches that determine identity of each segment
• One Hox gene can switch on several genes
– E.g. Antp is the switch for all legs
– 2 families (no need to copy this)
• Regulation of head & thorax
• Regulation of thorax and abdomen
Drosophila body plan
• Head with 3 segments
– Md, Mx and Lb
• Thorax with 3 segments
– T1, T2, T3
• Each segment has a pair of
legs
• T2 has wings
• T3 has halters (for balance)
• Abdomen with 8 segments
This is more detail than you need to know – just focus on the thorax
Mutant fly with 2 wings
Normal adult fly
• Ubx gene – stops
wings forming in T3
Bithorax mutant
• If the fly has a
mutation in both
copies of Ubx:
• wings grow in
T3 instead of
halters.
The pattern of homeobox expression
3’
5’
proboscipedia
Ultrabithorax
Antennapedia
Abdominal A
Sex comb reduced
The Antennapedia phenotype
• Legs in place of antennae
– Locate section f in your worksheet
• the Antennapedia (Antp) gene
• Normal Antp expression
– switched ON in the thorax to produce legs
– switched OFF in the head
• Gain of function:
– mutation of Antp causes abnormal Antp
expression in the head
– Antp transforms the head segment into thoracic
segment with legs!!!
Drosophila and human Hox genes
Mammals
•
• Homeobox (Hox )genes
• In 4 clusters
Hox A: Chr. 16
Hox B: Chr. 11
Hox C: Chr 15
Hox D: Chr. 2
• 38 Hox genes
Evolution of Hox gene cluster
Hypothetical
common
ancestor
Amphioxus
The Hox genes
in different
species
• All animals have
homologous (similar)
Hox genes
• These genes are highly
conserved (retained)
– Therefore
fundamental to the
development of an
animal
Haeckel's 1874 version of vertebrate embryonic development.
The top row shows an early stage common to all groups, the second row shows a
middle stage of development, and the bottom row shows a late stage embryo.
What is an animal?
From the book of “Bunny Suicides”
Textbook definition:
an organism that feeds, moves and responds to stimuli.
No need to learn this and the next slide
– but link it with the Classification topic in year 12
An animal is an organism that displays a particular spatial pattern of
gene expression (zootype)
Patterns of gene expression give us
a more accurate basis for classification
Slack et al. Nature 361 (1993), 490-492
Recall phylogenetic trees from year 12
Discuss the positions of the Fungi and the Green plants
Slack et al. Nature 361 (1993), 490-4
The genome duplications
• Larger Hox gene number
More complicated body pattern
Nematodes (round worms) = 1 Hox cluster
Drosophila = 2
Verteberates = 4
The genome duplications
Further reading
• Vitamin A and pregnancy
• Homeobox genes in plants and fungi