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A homeobox is a certain DNA sequence that is part of many genes involved in the regulation of the development (morphogenesis) of animals. Genes that have a homeobox are called Hox genes and form the Hox gene family.

A homeobox is about 180 base pairs long; it encodes a protein domain (the homeodomain) which can bind to DNA. The Hox genes code for transcription factors which typically switch on a whole cascade of other genes, for instance all the ones needed to make a leg. While the homeobox domain itself binds unspecifically to all DNA strands, other parts of the Hox gene will ensure that the resulting transcription factor binds only to precisely defined sequences.

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 Hox 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. Versions of the homeobox have even been found in one-cellular yeasts and prokaryotes. This suggests that this gene family evolved very early and that the basic mechanisms of morphogenesis are the same for many organisms.

It is theorized that natural selection over millions of years has acted upon the results of small mutations in these genes to form more complex organisms. Point mutations in early non-segmented animals, for example, led to segmentation and later, the development of other appendages such as limbs or antennae.

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