Homeobox

Overview
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.

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, for instance all the ones needed to make a leg. 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
A particular subgroup of homeobox genes are the Hox genes, which are found in a special gene cluster, the Hox cluster (also called Hox complex).

Hox genes function in patterning the body axis. Thus, by providing the identity of particular body regions, Hox genes determine where limbs and other body segments will grow in a developing fetus or larva.

Mutations in any one of these genes can lead to the growth of extra, typically non-functional body parts in invertebrates, for example antennapedia complex in Drosophila, which results in a leg growing from the head in place of an antenna and is due to a defect in a single gene.

Mutation in vertebrate Hox genes usually results in miscarriage.

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 have been identified.

Non-human
Homeobox genes have even been found in fungi, for example the one-cellular yeasts, and 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 once in the early evolution of animals and once again in the early evolution of plants.

Human genes
Humans generally contain homeobox genes in four clusters:

There is also a "distal-less homeobox" family:, , , , , and.

"HESX homeobox 1" is also known as.

Short stature homeobox gene is also known as.

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.