Homeotic mutations

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Homeotic mutations

• We know some misterious mutations, which
  generate horroristic monsters

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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

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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
  region-specific in the embryo

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• The homeotic transformations got known first in
  Drosophyla
• The regulation of Hox expression and the role of
  Hox genes is well known in Drosophyla

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Hierarchy of genes in Drosophila development
Maternal factor
Development of the number of segments
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Hierarchy of genes in Drosophila development
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Organization of Drosophila Hox genes
HOM-C complex
Antennapedia complex
Bithorax complex
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The pattern of Hox expression
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labial
proboscipedia
Abdominal B
Ultrabithorax
deformed
Antennapedia
Abdominal A
Sex comb reduced
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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.

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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 arent 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

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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 isnt 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!!!

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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

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Mammalian Hox genes

• In mice and human 4 Hox clusters have been found
  
• Homology has been found between the Drosophyla
  and human Hox genes

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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
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Archetypal organisation of Amphioxus Hox gene
cluster
The evolution of the Hox clusters

• Jordi Garcia-Fernandez Peter W. H. Holland
• Nature, 1994, vol. 370

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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)

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The Amphioxus Hox gene cluster

• The Amphioxus genome has only one Hox cluster
• It contains homologues of the mammalian Hox genes

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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

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Evolution of Hox gene cluster
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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
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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

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The genome duplications
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The genome duplications

• Larger Hox gene number

More complicated body pattern