homeotic mutations we know some misterious mutations, which generate horroristic monsters
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Homeotic Homeotic mutationsmutations
We know some misterious mutations, which We know some misterious mutations, which generate horroristic monstersgenerate horroristic monsters
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 region-
specific 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
Realisator genes
Maternal factor
Pair rule genes
Gap genes
Development of the number of segments
Development of the features of the segments
Selector genes (Selector genes (HoxHox genes) genes)
Hierarchy of genes in Drosophila development
bicoid (maternal factor)
hunchback (gap gene)giant (gap gene)
Krüppel (gap gene)
Organization of Organization of DrosophilaDrosophila HoxHox genesgenes
AntennapediaAntennapedia complex complex BithoraxBithorax complex complex
HOM-C complexHOM-C complex
3’5’
The pattern of The pattern of HoxHox expression expression
labialproboscipedia
deformed
Sex comb reduced
Antennapedia
Ultrabithorax
Abdominal A
Abdominal B
3’5’
The pattern of The pattern of HoxHox expression expression
• ColinearityColinearity between between the order of the the order of the HoxHox genes and the genes and the expression pattern expression pattern along the A/P axis, for along the A/P axis, for example:example:– in the first position of in the first position of
the HOM-C comlex is the HOM-C comlex is the the labiallabial, and it has , and it has the most anterior the most anterior expression.expression.
The pattern of The pattern of HoxHox expression expression– the first the first lablab is expressed alone is expressed alone
– the second the second pbpb is expressed with is expressed with lab, lab, etc.etc.
– the last the last Abd-BAbd-B is expressed with is expressed with all the othersall the others
– there aren’t wings, or legs on the there aren’t wings, or legs on the abdomen –WHY??abdomen –WHY??
– The more posterior Hox gene The more posterior Hox gene supresses the affect of more supresses the affect of more anterioranterior
– For example: For example: UbxUbx, , AbdAAbdA and and AbdBAbdB supresses the development supresses the development of the legsof the legs
Elucidation of Antennapedia Elucidation of Antennapedia phenotypephenotype
• There are legs in the place of antennaeThere are legs in the place of antennae• This segment of the head looks like a This segment of the head looks like a
thoracal segmentthoracal segment• Normally, the Normally, the AntpAntp isn’t expressed in the isn’t expressed in the
headhead• Gain of function mutation of Gain of function mutation of AntpAntp causes causes
abnormal abnormal AntpAntp expression in the head expression in the head • The more posterior The more posterior HoxHox gene dominates gene dominates
above the more anteriorabove the more anterior• AntpAntp transforms the head segment into transforms the head segment into
thoracal segment!!!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
lblbpbpb
DfdDfdUbxUbx
AbdBAbdB
eveeve
otdotd
emsems
ScrScr
Mammalian Mammalian HoxHox genes genes
• In mice and human 4 In mice and human 4 HoxHox clusters have clusters have been found been found
• Homology has been found between the Homology has been found between the DrosophylaDrosophyla and human and human HoxHox genes genes
DrosophylaDrosophyla and human Hox genes and human Hox genes
4 clusters:4 clusters: Hox A: Chr. 16Hox A: Chr. 16 Hox B: Chr. 11Hox B: Chr. 11 Hox C: Chr 15Hox C: Chr 15 Hox D: Chr. 2Hox D: Chr. 2
13 paralog groups13 paralog groups
38 Hox genes38 Hox genes
Archetypal organisation of Archetypal organisation of AmphioxusAmphioxus HoxHox gene cluster gene clusterJordi Garcia-Fernandez & Peter Jordi Garcia-Fernandez & Peter W. H. HollandW. H. Holland
Nature, 1994, vol. 370Nature, 1994, vol. 370
The evolution of the The evolution of the HoxHox clustersclusters
The evolution of the The evolution of the HoxHox clusters clusters
• The changes in The changes in HoxHox gene number gene number and genomic organization played and genomic organization played an important role in metazoan an important role in metazoan body-plan evolutionbody-plan evolution
• Garcia-Fernandez and Holland Garcia-Fernandez and Holland examined the organisation of examined the organisation of HoxHox genes in cephalochordate genes in cephalochordate AmphioxusAmphioxus (Brachiostomata (Brachiostomata floridae)floridae)
The The AmphioxusAmphioxus HoxHox gene cluster gene cluster
• The The AmphioxusAmphioxus genome has only one genome has only one HoxHox clustercluster
• It contains homologues of the mammalian It contains homologues of the mammalian HoxHox genesgenes
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 clusterVertebrata genome contains 4 Hox clusters, Vertebrata genome contains 4 Hox clusters, DrosophylaDrosophyla genome contains only one genome contains only one
In general: we can see one-to-four relationship In general: we can see one-to-four relationship between invertebrate and vertebrate gene between invertebrate and vertebrate gene number (for example insulin receptor, notch …)number (for example insulin receptor, notch …)
Two genome duplications happenedTwo genome duplications happened
The Cambrian explosionThe Cambrian explosion
• Nearly all the extant phyla of kingdom Nearly all the extant phyla of kingdom Animalia emerged within few tens of Animalia emerged within few tens of million yearsmillion years
• This evolutionary explosion started about This evolutionary explosion started about 530 million years ago530 million years ago
• The assumed cause of it the genome The assumed cause of it the genome duplicationduplication