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Two clusters of Drosophila homeotic genes: Antennapedia-complex (ANT-C) Bithorax-complex (BX-C) Hox genes Mammals have 4 clusters of Hox genes Most likely produce by duplications of an ancestral Hox gene complex Maintenance of Homeotic Genes Expression Patterns Trithorax-group: Maintain homeotic genes in ON state. Maintain active chromatin structure. Polycomb-group: Maintain transcriptional SILENCE of homeotic genes. Maintain repressive chromatin structure. Both involve covalent modifications of histones. (Acetylation/Deacetylation & Methylation) Collectively, help to maintain determined states of cells. Mouse Hox gene expression Hoxc-8 mutant L1 = 1st lumbar vertebra WT: L1 does not have ribs Hoxc-8- mutant: L1 develops like a more anterior vertebra (homeotic phenotype) Hoxc-8- mutants are viable and have additional phenotypes Subdivision of vertebrate hindrain by Hox gene expression r = rhobdomere r2 r4 r3 r5 r7 Evo-Devo Changes in adult bodies are due to changes in development. Animal bodies have a modular construction: Made up of serially repeated parts Ex: Multiple segments in insects Multiple vertebrae in vertebrates Major themes in evolution Change number of repeating units Modify forms & specializations of a subset of repeating units In most cases, this does not involve the evolution of new genes Most developmental changes due to: Changes in patterns of expression of Hox & other genes that control pattern formation. • This is caused by changes in their regulatory elements Changes in the regulatory regions of genes that they regulate (effector genes). head neck Hoxc6 expression marks boundary between neck and trunk vertebrae trunk Based on patterns of gene expression, it appears that insect wings evolved from gill branches of aquatic crustaceans Evidence: Apterous & nubbin are required for fly wing development. Homologs of these genes are expressed in the respiratory lobes of modern crustacean limbs. Cis-regulatory region of a wing-promoting gene These Hox proteins suppress wing formation by repressing this wing-promoting gene By changing which effector genes are regulated by Ubx, different forms of insect hindwing have evolved from the ancestral hindwing effector genes How are the different patterns on butterfly wings formed? Some, but not all butterfly wings have eyespots Expression of Distal-less (a homeodomain TF) in butterfly wing imaginal discs correlates with presence or absence of eyespots in different species. Distal-less expression marks center of future eyespots Spalt protein Engrailed protein Concentric circles of pigmented scales due to expression of other regulatory genes in response to Distal-less GDF5 (a TGFb-family protein, similar to fly DPP) expression marks where joints will develop in digits Scleraxis (a conserved TF) expression marks where tendons in limbs & digits will develop BMP4 (a TGFb-family protein) expression marks tissue in between digits that will be lost by apoptosis Patched (homolog of fly segment polarity gene) expression marks where feather buds will develop in chick embryos. Eyeless = selector gene for eye development Ectopic expression of eyeless ectopic development of eye tissue Mouse gene: Small eyes Humans: Aniridia