Hox gene
Hox genes are a family of regulatory genes. Their gene products are transcription factors that control the activity of other, functionally related genes in the course of individual development ( morphogenesis ). So you belong to the homeotic genes. The characteristic part of a Hox gene is a homeobox. It is a characteristic sequence of homeotic genes. The Homöoboxen encode in the cells for definable specific protein domains or protein domains ( homeodomains ). These are usually made of 60 amino acids and have a DNA - binding domain. The base sequence of the homeobox is very similar in all Hox genes of any animal. This leads to the conclusion that it has been preserved in the evolutionary history; obviously, mutations appear here mostly from lethal.
Tasks
The primary task of Hox genes is the outline of the embryo along the longitudinal body axis (anatomical cranio -caudal axis). This task they fulfill in all animals that have a body axis. Orders have different strains or a different number of Hox genes, which are expressed during embryonic development in each case in a particular section. This results in a sequence of strips inside the Embryonalgewebes. The cells of this strip obtained by a layer of information about their position in the developing embryo; their further division, their differentiation and, if you programmed cell death (apoptosis ) take place this situation accordingly. Particularly striking is the training and the specific form of extremities. In insects, the Hox genes determine whether extremities plants originate in one segment. Later they regulate then what type is formed by the extremities (eg, antennae, mouthparts, legs, wings ). In the vertebrate embryo ( in humans ), the Hox genes determine, among other things, the design and shape of the vertebrae ( cervical, thoracic vertebrae, lumbar vertebrae) and ribs. The core group of insects ( Arthropoda ) and vertebrates ( Chordata ) are segmented organisms. Hox genes are involved but in organisms with no segments in the same way in the organization.
The second body axis of bilaterians, the back -to-front axis ( anatomically: Dorsal - ventral axis) is not controlled by Hox genes. Other transcription factors are responsible for determining it: decapentaplegic or bone morphogenetic protein ( Dpp / Bmp ) and short gastrulation or chordin (suction / CHRD ).
Evolution
The Hox genes are only one component of a larger family of genes, each with similar functions. In addition to the Hox genes, the families of the ParaHox genes and the so-called NK genes exist (named after their discoverers Niremberg and Kim). With some other, smaller gene families, they form the so-called ANTP mega cluster. The respective families may have a special relationship with each one of the embryonic germ layers: Hox to neuroectoderm, ParaHox the endoderm, mesoderm to NK. If this theory would be confirmed, this would have profound implications for the reconstruction of the common tree of the animal phyla.
All genes belonging to this so have large agreement in their base sequence and off the homeobox on that one accepts their origin by gene duplication from a single Ursprungsgen. Genes from the ANTP mega clusters were found in all multicellular animals then examined. They appeared in any previously studied on single-celled organisms ( protozoa ), in particular not in the choanoflagellates, which are generally regarded as the sister group of multicellular animals, that is, among the protozoa are closest related to them. The gene family must therefore have existed already in the common ancestor of all Metazoa ( in the Precambrian ). Actual Hox genes are common to all strains of animals with the exception of sponges, the Ctenophora (and possibly the Placozoa ) together. The cnidarians ( Cnidaria ) two Hox genes exist. The most primitive Bilateria, the acoelomorphen flatworms, have four. In all more highly organized animal strains, the relationships are more complicated, because in different lines, individual Hox genes split ( doubled) and others have disappeared. Thus, the remaining Hox genes themselves do not always correspond directly, even if their number is possibly the same. Arthropods and mollusks have, for example both on nine Hox genes.
Most complicated are the conditions in which ordinary About the deuterostomes, which also includes the vertebrates. The lancelet amphioxus, the last surviving representatives of the acrania ( Acrania ), which are considered next of kin of the ancestors of the higher vertebrates, has fifteen Hox genes. The four-footed vertebrates ( Tetrapoda ) have 39 Hox genes, which can be divided into four gene clusters. It is now generally accepted that the vertebrate genome (including the Hox genes ) has completely doubled twice in the course of evolution. Today's number is caused by the subsequent loss of individual genes at a later date about. Even more Hox genes have different lines of development in bony fish, where it came to the elimination of the Tetrapoda to further Genverdoppelungen.
The Hox genes more highly organized of all strains can be grouped into four gene families, which are attributed to the four Hox genes of Urbilateriers. The individual genes within the different tribes, in many cases parallelize the basis of their base sequences, that is, they are probably emerged from the same Ursprungsgen the common ancestor of both lines ( homologous ).
Regulation
Hox proteins are transcription factors, which assign different body regions different identities. This is done by regulating numerous behind it ( in the jargon of geneticists: " downstream " ) situated genes, many of which are controlled by several Hox proteins. In a particular segment small differences in the location and timing of Hox gene expression play an important role in the fate of developing organs and cell lines. Some Hox genes have taken on roles in addition to the cellular pattern formation ( location information).
Particularly striking is that the order of Hox genes on the chromosome corresponds to the order of the parts of the body controlled by them. At least in vertebrates corresponds to this also the order of their temporal expression. In addition, the Hox genes are arranged mostly in a single (or few) sections directly adjacent to the DNA strand. This rule of an arrangement suggesting underlying regulatory processes that are conserved in large parts of the animal kingdom. It is called collinearity.
Hox genes interact with other transcription factors, but also on numerous (sometimes hundreds ) of effector genes, which they can on or off in the manner of a switch. To this end, they overlap, like all transcription factors, to one of the protein-coding sequence of the gene adjacent section (so-called cis-regulatory sequence ) to. Hox genes are controlled by others in the organization formerly distinct transcription factors. These controlling elements are extremely difficult to investigate in detail. Some findings are from the most important model organism for geneticists, the fruit fly Drosophila before. Thus, the regulatory sequences are organized into modules which in each case by a "buffer" ( separating members ) are shielded from each other. While the base sequence of the Hox genes is evolutionarily conserved, the cis-regulatory sections proved already at eight different fruit fly species to be very different. Within this total variable ensembles but there are obviously shorter domains that are so similar between different species that switch of a type could be controlled by proteins of a different kind. About the expression of individual Hox gene decide initiator elements within the respective module. In addition, there are other regulatory proteins that turn off all the modules or can hold in expressionsfähigem state by changing the "packaging" of DNA in chromatin Histonkomplexen. Overall, the conditions are extremely complicated, and their research is in its infancy. The orders of magnitude can be estimated approximately by the fact that the regulatory sequences comprise at a particular Hox gene of Drosophila ( Ubx ) 98 percent of the total size of the protein-coding section 2 percent.
If a Hox protein expressed by a natural or artificially induced mutation in the wrong body part ( ectopic ), this has serious consequences for development. This results in severe deformities in which organs or appendages arise in the wrong place and may change the identity of entire segments in the body. One speaks here of homeotic transformations and mutations. For example, in the fruit fly instead of sensors grow legs ( " Antennapedia " ), or in place of abdominal segments, the thoracic doubled ( " bithorax "). Such homeotic mutations were discovered by geneticists as early as 1915. They eventually led to the discovery of Hox genes. Homeotic mutations usually lead to death. In humans, for example, the formation of additional fingers ( polydactyly ) is probably due to a homeotic mutation.
Evolutionary Developmental Biology
The discovery of Hox genes was probably the most important catalyst for the emergence of a new research direction: The Evolutionary Developmental Biology (English: evolutionary developmental biology, often abbreviated to " Evo -devo "). The fact that it was now possible for the first time to explore the genetic basis of basic developmental mechanisms directly, the special importance of the individual ( ontogenetic ) development for evolutionary basis for a whole new research program has become. It is important about the importance of developing mechanical constraints on the direction and speed of evolutionary processes, especially that now are an actual genetic basis for basic body plans, and thus opportunities for their evolutionary change for the first time recognizable. Different expression of Hox genes repetitive tasks you such as the development of the body sections ( tagmata ) of the insects from similarly segmented precursors or the origin of the body blueprint of snakes from lizard-like precursors understand. Other significant findings concern the relationships at the very base of the family tree of the animals, that is, so far completely enigmatic events as the emergence of animal phyla are much better understandable.
About the actual role of Hox genes themselves within these changes, there are still controversial ideas within science. Some scholars are of the view new body plans could occur so new about a small mutation in a quasi step. Imagine the emergence of a new blueprint so ago as a very rare, cheap homeotic transformation. Most scientists, however, about the other view. They have developed models, such as might be subject to the same changes very gradually by small shifts in the relationship of various Hox proteins.