Expansion of tandem gene clusters

Gene duplication by unequal crossing-over

Divergence of coding and regulatory sequences

Evolution of HOX clusters

The homeobox is a highly conserved DNA-binding domain

DrosophilaAmphioxusMouseHumanChickFrogFugu

Zebrafish

HOX4 homeodomain

Evolution of HOX clusters in vertebrates

Mouse

Fugu

Zebrafish

- Vertebrates have multiple HOX clusters

- Paralogous HOX genes may have partly redundant functions

- Some genes and clusters become specialized for distinct functions

- Different lineages lose some genes and acquire new functions for others

Using gene replacement to test HOX gene function

Using gene replacement to test HOX gene function

Functionally equivalent HOX paralogs

HOX gene labial required for tritocerebral commissure

Genetic rescue strategy

lab-Gal4 lab ; lab-Gal4 / UAS - lab-

red = HRP; green = Lab

Other HOX genes can partially substitute for lab

Other HOX genes can partially substitute for lab

Distinct roles of Ubx and abd-A in the midgut

dpp expression in the fly midgut is activated by Ubx, but repressed by abd-A

Activation and repression are mediated by the same binding sites within a dpp enhancer

Onychophoran Ubx causes homeotic transformations in Drosophila

Onychophoran Ubx can regulate some Drosophila target genes

dSRFdpp

Onychophoran Ubx cannot fully substitute for Drosophila Ubx

Chimeric Ubx proteins

Mapping the functional specificity of Onychophoran Ubx

Functional specificity of Ubx maps outside the homeodomain

Conservation and change in Ubx proteins

Mapping the functional specificity of Ubx proteins

Functional comparison of Drosophila and Artemia Ubx

Evolution of a new repression domain

Non-HOX functions of derived HOX genes

Maternal gradient of bicoid establishes Anterior-Posterior axis in the Drosophila embryo

bicoid gradient formation in Drosophila

zen functions in Dorso-Ventral patterning

sna

sog

zen

zen is a derived HOX gene

HOX-like expression of zen homologue in Cupiennius

Evolution of zen and bcd from an ancestral HOX gene

Genetic control of segmentation in Drosophila

Antennae

ftz deletion does not affect segmentation in Tribolium

HOX-like expression of the Chelicerate ftz homologue

Archegozetes longisetosus

Effects of ectopic ftz expression in Drosophila

Dm

Sg

en expression

36%

4%

A homeodomain-deficient ftz allele

ftz expression in Schistocerca

Tc-ftz

Sg-ftz

Dm-ftz

Tc-ftz

Dll-Gal4

Homeotic antenna to leg transformations

Tribolium ftz retains homeotic potential

wt Dm-ftz Tc-ftz Dm-Scr

wt Dm-ftz Tc-ftz Dm-Antp

Evolution of ftz function

Comparison of ftz proteins between Drosophila and Schistocerca

Expression and function of ftz-F1

ftz-F1 ftz

enftz-F1 mutant

ftz-F1 encodes a nuclear hormone receptor

Physical interaction between ftz and ftz-F1

Transcriptional activation by ftz / ftz-F1 complex

In yeast In Drosophila embryos

Novel functions of divergent HOX genes

Loss and gain of protein-protein interaction motifs