A homeobox is a stretch of DNA sequence found in genes involved in the regulation of the development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family.
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.
A particular subgroup of homeobox genes are the Hox genes, which are found in a special gene cluster, the HOX cluster. 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, but usually results in spontaneous abortion in vertebrates.
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. The diagram to the right is a structural model of the Rattus norvegicus Pit-1 homeobox-containing protein (purple) bound to DNA. Pit-1 is a regulator of growth hormone gene transcription. Pit-1 is a member of the POU DNA-binding domain family of transcription factors so it can bind to DNA using both the POU domain and the homeodomain. Homeobox genes have even been found in fungi, for example the one-cellular yeasts and plants. This suggests that this gene family evolved very early and that the basic mechanisms of morphogenesis are the same for many organisms.
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, 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.
In a loose analogy to computing, one can think of a homeobox gene like a call to a subroutine. It switches on the production of a whole subsystem, the code for which must already be present elsewhere in the DNA.