A homeobox is a DNA sequence found within genes that are involved in the regulation of patterns of anatomical development (morphogenesis) in animals, fungi and plants.
They were discovered independently in 1983 by Ernst Hafen, Michael Levine and William McGinnis working in the lab of Walter Jakob Gehring at the University of Basel, Switzerland, and Matthew P. Scott and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington.
A homeobox is about 180 base pairs long. It encodes a protein domain (the homeodomain) which when expressed (i.e. as protein) can bind DNA. The following shows the consensus 60-polypeptide chain corresponding to homeobox domain, with typical intron positions noted with dashes:
Homeobox genes encode transcription factors that typically switch on cascades of other genes. The homeodomain binds DNA in a sequence-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. Such complexes have a much higher target specificity than a single homeodomain protein. Homeodomains are encoded both by genes of the Hox gene clusters and by other genes throughout the genome.
 Hox genes
They are essential metazoan genes as they determine the identity of embryonic regions along the anterio-posterior axis. The first vertebrate Hox gene was isolated in Xenopus by Eddy De Robertis and colleagues in 1984, marking the beginning of the young science of Evo-devo.
In vertebrates, the four paralog clusters are partially redundant in function, but have also acquired several derived functions. In particular, HoxA and HoxD specify segment identity along the limb axis.
The main interest in this set of genes stems from their unique behaviour. They are typically found in an organized cluster. The linear order of the genes within a cluster is directly correlated to the order of the regions they affect as well as the timing in which they are affected. This phenomenon is called colinearity. Due to this linear relationship, changes in the gene cluster due to mutations generally result in similar changes in the affected regions.
Homeobox gene expression in Drosophila melanogaster
For example, when one gene is lost the segment develops into a more anterior one, while a mutation that leads to a gain of function causes a segment to develop into a more posterior one. This is called ectopia. Famous examples are Antennapedia and bithorax in Drosophila, which can cause the development of legs instead of antennae and the development of a duplicated thorax, respectively.
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.
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 bilateria but more recently cnidaria 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.
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 Hox genes in four clusters:
Full article ▸