User:Futuremicrobe/Hox gene

Article Draft
Copied from Hox gene leader, editing to clarify, add citations, and tighten the prose.

Lead
~edited version~

Hox genes are a family of genes which encode regulatory transcription factors responsible for regulating segmentation in bilaterians, primarily along the anterior-posterior (A-P) axis but also in other organ systems. They function by activating or repressing downstream genes, including themselves, in a variety of tissues throughout development, ultimately specifying segment identity along the A-P axis.

Hox genes were first characterized in the fruit fly Drosophila melanogaster by Edward B. Lewis in 1978. They were called "homeotic" genes, as mutations in these genes caused homeotic transformations in which one body part appears to be replaced by another. Early sequencing of the D. melanogaster genome found that these homeotic genes shared a conserved stretch about ~180bp in length, dubbed the "homeobox". As sequencing became more tractable, more genes containing this conserved sequence have been discovered, such that "homeobox" or "homeotic" now refer to a wider group of genes, while "Hox" still refers specifically to the conserved subset of homeobox genes involved in segmentation specification.

In addition to being required for normal development, Hox genes are an area of intense interest in the fields of genetics and evolution due to the unique correspondence between the ordering of Hox genes along the chromosome and the domain and timing of their expression, termed spatial colinearity. In humans, mutations in Hox genes can lead to developmental defects such as anomalies in the hands and feet and aberrant Hox expression has been identified in several human cancers.

~original version~

Hox genes, a subset of homeobox genes, are a group of related genes that specify regions of the body plan of an embryo along the head-tail axis of animals. Hox proteins encode and specify the characteristics of 'position', ensuring that the correct structures form in the correct places of the body. For example, Hox genes in insects specify which appendages form on a segment (for example, legs, antennae, and wings in fruit flies), and Hox genes in vertebrates specify the types and shape of vertebrae that will form. In segmented animals, Hox proteins thus confer segmental or positional identity, but do not form the actual segments themselves.

Studies on Hox genes in ciliated larvae have shown they are only expressed in future adult tissues. In larvae with gradual metamorphosis the Hox genes are activated in tissues of the larval body, generally in the trunk region, that will be maintained through metamorphosis. In larvae with complete metamorphosis the Hox genes are mainly expressed in juvenile rudiments and are absent in the transient larval tissues. The larvae of the hemichordate species Schizocardium californicum and the pilidium larva of Nemertea do not express Hox genes.

An analogy for the Hox genes can be made to the role of a play director who calls which scene the actors should carry out next. If the play director calls the scenes in the wrong order, the overall play will be presented in the wrong order. Similarly, mutations in the Hox genes can result in body parts and limbs in the wrong place along the body. Like a play director, the Hox genes do not act in the play or participate in limb formation themselves.

The protein product of each Hox gene is a transcription factor. Each Hox gene contains a well-conserved DNA sequence known as the homeobox, of which the term "Hox" was originally a contraction. However, in current usage the term Hox is no longer equivalent to homeobox, because Hox genes are not the only genes to possess a homeobox sequence; for instance, humans have over 200 homeobox genes, of which 39 are Hox genes. Hox genes are thus a subset of the homeobox transcription factor genes. In many animals, the organization of the Hox genes in the chromosome is the same as the order of their expression along the anterior-posterior axis of the developing animal, and are thus said to display colinearity. Production of Hox gene products at wrong location in the body is associated with metaplasia and predisposes to oncological disease, e.g. Barrett's esophagus is the result of altered Hox coding and is a precursor to esophageal cancer.