Download Hox genes

We know some misterious mutations, which
generate horroristic monsters
Homeotic
mutations
The homeosis
• Mutation, that causes transformation of an
area of the body into another area
• The mutated genes the so-called
Homeobox genes, shortly Hox genes
Products of Hox genes
• The Hox genes contain a 180 bp conservated region:
the homeobox
• The homeobox encodes a 60 AA length
homeodomain = a DNA-binding helix turn helix motif
• The homeodomain proteins are transcription factors
• The Hox genes are selector genes (regulate the
expression of other so-called realisator genes)
• The expression of several Hox genes is regionspecific in the embryo
• The homeotic transformations got known first in
Drosophyla
• The regulation of Hox expression and the role
of Hox genes is well known in Drosophyla
Hierarchy of genes in Drosophila
development
Maternal factor
Gap genes
Development
of the
number of
segments
Pair rule genes
Selector genes (Hox genes)
Realisator genes
Development
of the features
of the
segments
Hierarchy of genes in Drosophila
development
giant (gap gene)
hunchback (gap gene)
bicoid (maternal factor)
Krüppel (gap gene)
Organization of Drosophila Hox
genes
HOM-C complex
Antennapedia complex
3’
Bithorax complex
5’
The pattern of Hox expression
3’
5’
Abdominal B
proboscipedia
Ultrabithorax
Antennapedia
Abdominal A
deformed
Sex comb reduced
labial
The pattern of Hox expression
• Colinearity between
the order of the Hox
genes and the
expression pattern
along the A/P axis, for
example:
– in the first position of
the HOM-C comlex is
the labial, and it has
the most anterior
expression.
The pattern of Hox expression
– the first lab is expressed alone
– the second pb is expressed with
lab, etc.
– the last Abd-B is expressed with
all the others
– there aren’t wings, or legs on the
abdomen –WHY??
– The more posterior Hox gene
supresses the affect of more
anterior
– For example: Ubx, AbdA and
AbdB supresses the
development of the legs
Elucidation of Antennapedia
phenotype
• There are legs in the place of antennae
• This segment of the head looks like a
thoracal segment
• Normally, the Antp isn’t expressed in the
head
• Gain of function mutation of Antp causes
abnormal Antp expression in the head
• The more posterior Hox gene dominates
above the more anterior
• Antp transforms the head segment into
thoracal segment!!!
What are the animals?
• An animal is an organism that displays a particular
spatial pattern of gene expression. This pattern is the
zootype.
• Every animal use the same regulation method to the
developing of very different structures
pb
otd
lb
Scr Ubx
Dfd
AbdB
eve
ems
Mammalian Hox genes
• In mice and human 4 Hox clusters have
been found
• Homology has been found between the
Drosophyla and human Hox genes
Drosophyla and human Hox genes
4 clusters: Hox A: Chr. 16
Hox B: Chr. 11
Hox C: Chr 15
Hox D: Chr. 2
13 paralog groups
38 Hox genes
The evolution of the Hox
clusters
Archetypal organisation of
Amphioxus Hox gene cluster
Jordi Garcia-Fernandez & Peter
W. H. Holland
Nature, 1994, vol. 370
The evolution of the Hox clusters
• The changes in Hox gene number
and genomic organization played
an important role in metazoan
body-plan evolution
• Garcia-Fernandez and Holland
examined the organisation of Hox
genes in cephalochordate
Amphioxus (Brachiostomata
floridae)
The Amphioxus Hox gene cluster
• The Amphioxus genome has only one Hox
cluster
• It contains homologues of the mammalian Hox
genes
Relationship of the Amphioxus and
mammalian Hox genes
• The sequence of homeobox of 10
Amphioxus Hox genes have been analised
• It has been compared with members of
mammalian paralog groups
• Conservative amino-acid residues have
been found
Evolution of Hox gene cluster
Hypothetical
common
ancestor
Amphioxus
Evolution of Hox gene cluster
Vertebrata genome contains 4 Hox clusters,
Drosophyla genome contains only one
In general: we can see one-to-four relationship
between invertebrate and vertebrate gene
number (for example insulin receptor, notch …)
Two genome duplications happened
The Cambrian explosion
• Nearly all the extant phyla of kingdom
Animalia emerged within few tens of
million years
• This evolutionary explosion started about
530 million years ago
• The assumed cause of it the genome
duplication
The genome duplications
The genome duplications
• Larger Hox gene number
More complicated body pattern