Homeobox

A homeobox is a DNA sequence found within genes that are involved in the regulation of development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family.

The most studied and the most conserved group of homeodomain protein are the Hox genes, which control segmental patterning during development, however not all homeodomain protein are Hox protein.

Discovery

They were discovered independently in 1983 by Walter Jakob Gehring and his colleagues at the University of Basel, Switzerland, and Matthew Scott and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington.

Homeodomain

A homeobox is about 180 base pairs long; it encodes a protein domain (the homeodomain) which can bind DNA.

Homeobox genes encode transcription factors which typically switch on cascades of other genes. The homeodomain binds DNA in a specific manner.

However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors, often also homeodomain proteins. Such complexes have a much higher target specificity than a single homeodomain protein.

Hox genes

Main article: Homeotic genes

Molecular evidence shows that some limited number of Hox genes have existed in the Cnidaria since before the earliest true Bilatera, making these genes pre-Paleozoic.

Joseph F. Ryan1,4, Maureen E. Mazza2, Kevin Pang3, David Q. Matus3, Andreas D. Baxevanis4, Mark Q. Martindale3, John R. Finnerty1,2*

They are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis.

In vertebrates the 4 paralogue clusters are partially redundant in function, but have also acquired several derived functions in particular HoxA and HoxD specify the segment identity along the limb axis.

The main interest in this set of genes stems is their unique behaviour. They are mostly found clustered together and the order they are found generally matches the order of regions they affect and their timing, a phenomenon called collinearity. Due to this balance, generally, when one gene is lost the segment becomes a more anterior one, while a gain of function mutant (ectopic) will be more posterior, famous examples of these are Antennapedia and bithorax in Drosophila.

Diversity

The homeobox genes were first found in the fruit fly Drosophila melanogaster and have subsequently been identified in many other species, from insects to reptiles and mammals.

Homeobox genes were previously only identified in bilaterians but recently, cnidarians have also been found to contain homeobox domains and the "missing link" in the evolution between the two has been identified.

Homeobox genes have even been found in fungi, for example the unicellular yeasts, and in plants.

Plants

The well known homeotic genes in plants (MADS-box genes) are not homologous to Hox genes in animals. Plants and animals do not share the same homeotic genes, and this suggests that homeotic genes arose independently in the early evolution of animals and plants.

Human genes

Humans generally contain homeobox genes in four clusters:

name	chromosome	gene
HOXA (or sometimes HOX1) - HOXA@	chromosome 7	HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11, HOXA13
HOXB - HOXB@	chromosome 17	HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXB7, HOXB8, HOXB9, HOXB13
HOXC - HOXC@	chromosome 12	HOXC4, HOXC5, HOXC6, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12, HOXC13
HOXD - HOXD@	chromosome 2	HOXD1, HOXD3, HOXD4, HOXD8, HOXC9, HOXD10, HOXD11, HOXD12, HOXD13

There is also a "distal-less homeobox" family: DLX1, DLX2, DLX3, DLX4, DLX, and DLX6.

"HESX homeobox 1" is also known as HESX1.

Short stature homeobox gene is also known as SHOX. also a home gene controls the diffirensation of cells and tissue in the embryo.

Mutations

Mutations to homeobox genes can produce easily visible phenotypic changes.

Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be (antennapedia), and a second pair of wings.

Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution of segmented animals.

Interestingly, there is one insect family, the xyelid sawflies, in which both the antennae and mouthparts are remarkably leg-like in structure. This is not uncommon in arthropods as all arthropod appendages are homologous.

Regulation

The regulation of Hox genes is highly complex and involves reciprocal interactions, mostly inhibitory. Drosophila is known to use the Polycomb and Trithorax Complexes to maintain the expression of Hox genes after the down-regulation of the pair-rule and gap genes that occurs during larval development. Polycomb-group proteins can silence the HOX genes by modulation of chromatin structure.

See also

• Evolutionary developmental biology
• Body plan

References

• Lodish; et al. (2003). Molecular Cell Biology (5th Edition ed.). New York: W.H. Freeman and Company. ISBN 0-7167-4366-3. {{cite book}}: |edition= has extra text (help); Explicit use of et al. in: |author= (help)
• Ogishima S (2007). "Missing link in the evolution of Hox clusters". Gene. 387 (1–2): 21–30. doi:10.1016/j.gene.2006.08.011. PMID 17098381. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

External links

• Homeodomain Resources provided by Thomas R. Bürglin
• Discovering the Homeobox
• Homeobox at the U.S. National Library of Medicine Medical Subject Headings (MeSH)