Гомеобокс

Гомеобокс ('homeobox) это последовательность ДНК, обнаруженная в генах, вовлеченных в регуляцию развития у животных, грибов и растений. Гены, которые содержат гомеобокс, образуют отдельное семейство.

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.

Открытие

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.

Гомеодомен

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. 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-гены

Основная статья: Homeotic genes

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.

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 (Carrasco, McGinnis, Gehring and De Robertis, Cell 37, 409—414, 1984).

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. For example, when one gene is lost the segment becomes a more anterior one, while a gain of function mutation (ectopic) will be more posterior. Famous examples are Antennapedia and bithorax in Drosophila.

Разнообразие

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.

У растений

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.

У человека

Humans generally contain homeobox genes in four clusters:

name	chromosome	gene
HOXA (or sometimes HOX1) - HOXA@	chromosome 7	HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11, HOXA13
HOXB - HOXB@	chromosome 17	HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXB7, HOXB8, HOXB9, HOXB13
HOXC - HOXC@	chromosome 12	HOXC4, HOXC5, HOXC6, HOXC8, HOXC9, HOXC10, HOXC11, HOXC12, HOXC13
HOXD - HOXD@	chromosome 2	HOXD1, HOXD3, HOXD4, HOXD8, HOXC9, HOXD10, HOXD11, HOXD12, HOXD13

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 gene is also known as SHOX.

Мутации

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.

Регуляция

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. Polycomb-group proteins can silence the HOX genes by modulation of chromatin structure.

Ссылки

• Lodish et al. Molecular Cell Biology. — 5th Edition. — New York : W.H. Freeman and Company, 2003. — ISBN 0-7167-4366-3.
• Ogishima S (2007). "Missing link in the evolution of Hox clusters". Gene. 387 (1–2): 21—30. doi:10.1016/j.gene.2006.08.011. PMID 17098381. {{cite journal}}: Неизвестный параметр |coauthors= игнорируется (|author= предлагается) (справка); Неизвестный параметр |month= игнорируется (справка)

Внешние ссылки

• Zhong YF, Butts T, Holland PWH, 2008. HomeoDB: база данных по разнообразию генов гомеобокса
• Ресурсы по гомеобоксу, by Thomas R. Bürglin
• Открытие гомеобокса