A homeobox is a
DNA sequencefound within genes that are involved in the regulation of patterns of development ( morphogenesis) in 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 proteins are Hox proteins.
They were discovered independently in
1983by Walter Jakob Gehringand his colleagues at the University of Basel, Switzerland, and Matthew Scott and Amy Weiner, who were then working with Thomas Kaufmanat Indiana University in Bloomington. [cite journal
title=A conserved DNA sequence in homoeotic genes of the Drosophila
coauthors=Levine MS, Hafen E, Kuroiwa A, Gehring WJ
pmid=6323992 | doi = 10.1038/308428a0] [cite journal
title=Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila
doi = 10.1073/pnas.81.13.4115]
A homeobox is about 180
base pairs long; it encodes a proteindomain (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 regionof 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.
Molecular evidence shows that some limited number of Hox genes have existed in the
Cnidariasince before the earliest true Bilatera, making these genes pre- Paleozoic. [cite journal| last = Ryan |first = Joseph F |coauthors = Maureen E. Mazza, Kevin Pang, David Q. Matus, Andreas D. Baxevanis, Mark Q. Martindale, John R. Finnertyl | title = Pre-Bilaterian Origins of the Hox Cluster and the Hox Code: Evidence from the Sea Anemone, Nematostella vectensis | journal = PLoS ONE | url = http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000153 | year = 2007 | volume = 2 | pages = e153 | doi = 10.1371/journal.pone.0000153 | issue = 1 | date = 2007-01 | unused_data = |accessdate 2008-04-30] 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
colinearity. 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 Antennapediaand bithorax in Drosophila.
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.
The well known
homeoticgenes in plants ( MADS-boxgenes) 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.
Humans generally contain homeobox genes in four clusters:
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 geneis also known as SHOX. also a home gene controls the diffirensation of cells and tissue in the embryo.
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
evolutionof segmented animals.
Interestingly, there is one
insectfamily, 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.
The regulation of Hox genes is highly complex and involves reciprocal interactions, mostly inhibitory.
Drosophilais known to use the Polycomb and TrithoraxComplexes 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 proteinscan silence the HOX genes by modulation of chromatinstructure.cite book |chapterurl=http://www.horizonpress.com/rnareg|author= Portoso M and Cavalli G|year=2008|chapter=The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press|id= [http://www.horizonpress.com/rnareg ISBN 978-1-904455-25-7] ]
Evolutionary developmental biology
title=Missing link in the evolution of Hox clusters
doi = 10.1016/j.gene.2006.08.011
* [http://homeodb.cbi.pku.edu.cn/ Zhong YF, Butts T, Holland PWH, 2008. HomeoDB: a database of homeobox genes diversity]
* [http://www.homeobox.cjb.net/ Homeodomain Resources provided by Thomas R. Bürglin]
* [http://www.hhmi.org/genesweshare/b120.html Discovering the Homeobox]
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