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Hox genes. Hox genes turned out to be more evolutionarily variable than previously thought

Hox genes are a large family of genes that regulate development different parts bodies of multicellular animals. It has been known for quite some time that these genes are very evolutionarily conserved: many of them are common even in organisms as distant from each other as insects and mammals. However, this conservatism is not absolute. A detailed study of the fate of one of the groups of Hox genes conducted by German geneticists showed that new genes in this group arose several times in different evolutionary branches. Even in such relatively related animals as chordates and echinoderms, their set is different. And the ancient common ancestor of all bilaterally symmetrical animals had significantly fewer Hox genes than most modern representatives.

Genes of the family Hox known as regulators individual development animals that control the differentiation of parts of their body (see: The work programs of Hox genes in larvae and adult annelids are fundamentally different, “Elements”, 05/27/2013). Most animals have several of these genes, and they have two important properties. First, Hox gene mutations cause a special type of deformity associated with the transformation of some body parts into others. In insects, for example, this may be the transformation of the abdominal segments into pectoral segments or the antennae into paws (Fig. 1). Genes with this effect are usually called homeotic (see also Homeotic gene). Second, Hox genes are extremely evolutionarily conserved. About 30 years ago it was shown that, for example, in insects (Drosophila fly) and vertebrates (mouse, human), their nucleotide sequences are very close.

Insects and vertebrates are not close relatives at all. They are as far apart from each other on the evolutionary tree as is generally possible for two bilaterally symmetrical animals (see: New data made it possible to clarify the pedigree of the animal kingdom, “Elements”, 04/10/2008). That is, their common ancestor was simultaneously the common ancestor of mollusks, echinoderms, flat, round and annelid worms and, in general, without exception, all members of the huge group of bilaterally symmetrical, or bilateria. If a mouse and a fly have a gene in common, this means that this common ancestor already had it.

Meanwhile, the fruit fly has eight Hox genes, and all of them have exact, one-to-one matches in vertebrates (Fig. 2). At least, this opinion was widespread for a long time.

Another feature of Hox genes is that the areas of activity (expression) of these genes are usually located along the body of the animal in the same order in which the genes themselves are physically located on the chromosome (Fig. 2). This is called the principle of collinearity. For convenience, Hox genes are usually divided into groups: “front”, “central” and “posterior”. In accordance with the principle of collinearity, these names refer to both the location of the genes themselves on the chromosome and the location of their expression areas in the body.

New work, done in the Applied Bioinformatics Lab, Department of Biology, Universität Konstanz, is devoted to the evolutionary fate of the central group of Hox genes. Both the Drosophila fly and vertebrates have three genes in this group; in Drosophila they are called Antp, Ubx And abd-A, and in vertebrates - Hox6, Hox7 And Hox8(Fig. 3). Based on their relative position, one can expect a one-to-one correspondence: to the gene Antp will match the gene Hox6, gene Ubx- gene Hox7, gene abd-A- gene Hox8. But is this really so?

Geneticists from Konstanz decided to understand the relationships of the central Hox genes by comparing them directly. As you know, the product of each gene is a protein, and a protein is a chain of amino acids, the sequence of which can be deciphered and written down. Quite a lot of amino acid sequences of Hox proteins are now known. Using special programs, German geneticists pairwise compared absolutely all available protein sequences - products of the central Hox genes - with each other, without looking at the gene number or what animal it came from. A series of such objective comparisons would reliably show which genes share a common origin and which do not.

It turned out that of the three central Hox genes, only one is actually common in insects and vertebrates. This is a gene called in insects Antp, and in vertebrates - Hox7. Only this gene was probably present in their common ancestor. Other central Hox genes in insects and vertebrates have nothing in common; they arose in these groups in different ways, as a result of independent gene duplications (doublings). For example, genes Hox6 And Hox8 are found only in vertebrates: they are not similar to any genes of other animals.

The fate of the gene found in Drosophila turned out to be interesting abd-A. It (or its close “relative”) is found not only in insects and even not only in arthropods, but also in several other types of animals, including mollusks, annelids and flatworms. Apparently, this gene is common to a huge group of protostomes (Protostomia). This group includes arthropods, mollusks and almost all worms. But vertebrates are not included, and they do not have this gene.

Two unusual central Hox genes are found in animals belonging to the phyla Echinodermata and Hemichordates. These two types are considered closely related, and indeed, their unique Hox genes - apparently evolutionarily acquired - are very similar. But chordates (which include, in particular, vertebrates) do not have these genes. Hemichordates, echinoderms and chordates together form the group Deuterostomia. The results obtained apparently mean that not only the common ancestor of bilaterally symmetrical animals, but also the common ancestor of deuterostomes had only one central Hox gene.

True, the common ancestor of deuterostomes also lived a very long time ago - more than 500 million years ago. So, these results generally confirm the high conservation of Hox genes. But we now clearly see that it is not absolute. The hypothetical “protoworm,” which was the ancestor of all bilaterally symmetrical animals, had a different set of Hox genes than a mouse or a fly (although in the wake of the first discoveries one might have thought so). It was still noticeably simpler. And its complication proceeded gradually, in different groups in different ways, through events, many of which are now known to us.

The work of geneticists from Konstanz shows that detailed description the evolutionary fate of individual genes can be very plot-driven - no worse than, for example, analyzing the biographies of historical characters. In the coming years, it is likely that more and more such studies will appear, based on extensive databases and the use of the latest software. Before our eyes, evolutionary genetics is entering a new stage of its development.

Sources: Stefanie D. Hueber, Jens Rauch, Michael A. Djordjevic, Helen Gunter, Georg F. Weiller, Tancred Frickey. Analysis of central Hox protein types across bilaterian clades: On the diversification of central Hox proteins from an Antennapedia/Hox7-like protein // Developmental biology(2013, preprint).

Evolution [Classical ideas in the light of new discoveries] Markov Alexander Vladimirovich

Hox genes gained freedom - and snakes lost their legs

Hox-genes gained freedom - and snakes lost their legs

Finally, consider research that sheds light on the role Hox-genes in the evolution of vertebrates. As is known, the most important function Hox-genes is that they mark the embryo in detail along the anterior-posterior axis. Further fate embryonic cells found in one or another part of the embryo depends on the set Hox-genes expressed in this part. For each Hox-gene is characterized by its own region of expression. For example, genes Hox12 And Hox13, as a rule, work only in the back part of the embryo, which will later become the tail; genes Hox10 in some vertebrates they work from the posterior end of the embryo to the line that will become the boundary between the thoracic region (where the vertebrae have ribs) and the lumbar region, where ribs do not develop. " Hox-code”, which determines the structural plan of the organism, is complex and not entirely the same in different groups of vertebrates. There can be little doubt that many major evolutionary transformations affecting body plan were associated with changes in structure and expression Hox-genes. However, there are still few well-studied examples illustrating this connection.

Hox - Drosophila and human genes. Rectangles Genes are indicated in the order in which they are located on the chromosomes. The fly has one set Hox - genes, in humans - four, partially duplicating each other (they were formed from one as a result of two whole-genome duplications). Clusters A, B, C, D are located on different chromosomes (in mice these are chromosomes No. 6, 11, 15 and 2, in humans - No. y, 17, 2, 12). In snakes, unlike mice and humans, cluster D lacks the 12th gene ( Hoxd12 ). In images of a fly and a human embryo, the expression areas of the corresponding genes are colored in the same colors as the genes themselves. According to the latest data, the correspondence between Hox -genes of arthropods and vertebrates are somewhat less clear than shown in this diagram.

In many animals, including vertebrates, Hox-genes in the genome are located in clusters, that is, in groups close to each other. The most surprising thing is that the order of genes in Hox-clusters often (though not always) coincide with the distribution of expression areas along the anterior-posterior axis: “head” genes are in front, followed by genes responsible for the formation of the middle parts of the body, and the cluster is closed by “rear” genes that control the development of the rear parts of the body. Apparently, this is due to the way expression is regulated Hox-genes: the section of DNA where it is located Hox-cluster gradually “opens up”, becoming available for transcription as it moves from the anterior end of the body to the posterior. Therefore, at the anterior end of the body, only the anterior ones are expressed. Hox-genes, and the closer to the tail, the more posterior genes are included in the work. A convenient way to regulate genes responsible for marking the embryo along the anterior-posterior axis!

The ancestors of vertebrates, like the modern lancelet, had one Hox-cluster including 14 genes. Two whole-genome duplications occurred early in vertebrate evolution. As a result, vertebrates acquired four Hox-cluster instead of one. This opened up great evolutionary opportunities for vertebrates (see Chapter 5). Separate Hox-genes were lost in some clusters, but in general their set and order remained similar in all four clusters. Paralogous genes (i.e. copies of the same Hox-gene in different Hox-clusters) acquired slightly different functions, which made it possible to finely regulate embryonic development and facilitate the development of new structural plans.

Biologists from Switzerland, New Zealand and the USA studied the work Hox-genes in squamate reptiles (order Squamata) (Di-Poi et al., 2010). This order, which unites lizards and snakes, is interesting for the variety of structural plans and variability of characters associated with the anterior-posterior differentiation of the body (relative length of body sections, number of vertebrae in them, etc.) Therefore, it was logical to assume that Hox-squamate clusters must have specific characteristics and that Hox-The genes of lizards and snakes must be different.

It was previously shown that areas of expression of the anterior Hox-genes in snakes have expanded posteriorly compared to other vertebrates. This is in good agreement with the overall elongation of the body. In addition, it was found that the rule of colinearity (i.e., the same order of genes in a cluster and the areas of their expression in the embryo) is strictly observed in snakes.

The researchers focused on the rear Hox-genes (from 10th to 13th). The main objects of the study were the whip-tailed lizard Aspidoscelis uniparens and corn snake Elaphe guttata. In addition, they were sequenced Hox-clusters of several other lizards, a tuataria and a turtle. For comparison we used Hox-chicken, human, mouse and frog clusters.

Rear set Hox-genes in all studied species turned out to be the same, except for the fact that the gene was “lost” in snakes and frogs Hoхd12(12th Hox-gene from the cluster D). Important changes were found in regulatory regions Hox-clusters. It turned out that all squamate reptiles have lost the regulatory region between genes Hoхd13 And Evх2, and snakes have also lost a conservative non-coding element between Hoхd12 And Hoхd13 and some regulatory regions in others Hox-clusters. An unexpected result was the presence in Hox-clusters of scaly sets of embedded mobile genetic elements. As a result, the total length of the rear part Hox-clusters in squamate have increased significantly compared to other terrestrial vertebrates.

All this seems to indicate that in squamates the evolutionary restrictions that prevent the accumulation of changes in the posterior part have been weakened. Hox-clusters. Purifying selection, which rejects similar changes in other vertebrates, was less effective in the evolution of lizards and snakes. This conclusion was confirmed during the analysis of coding regions Hox-genes. In these areas, lizards, and especially snakes, have accumulated many significant substitutions compared to other vertebrates. Some of them, apparently, were fixed by chance, due to the weakening of purifying selection, while others were fixed under the influence of positive selection, that is, they were useful.

Studying the nature of expression of the posterior Hox-genes in lizard and snake embryos confirmed the assumption that changes in the structure plan in the evolution of squamates were closely related to changes in the work of the hind legs. Hox-genes.

In the lizard, as in other terrestrial vertebrates, the leading edge of the region of gene expression Hoxa10 And Hoxc10 exactly corresponds to the border between the thoracic and lumbar regions. One of the functions of these genes is to suppress the development of ribs. Snakes do not have a lumbar region, and on the former sacral vertebrae (in snakes they are called cloacal vertebrae) there are special bifurcated ribs. Apparently, these features are due to the fact that Hox-genes in the ancestors of snakes lost the ability to stop the growth of ribs.

Expression area Hoxa10 And Hoxc10 in the snake it extends far into the thoracic region. These genes are also responsible for the timely cessation of growth of the thoracic region. Apparently, this function in snakes is also weakened, which could be one of the reasons for the lengthening of the thoracic region in snakes compared to their ancestors - lizards. The lengthening of the tail in snakes is due to the fact that of the four genes that “inhibit” the growth of the tail in lizards ( Hoxa13, Hoxc13, Hoxd13, Hoxd12) one gene in snakes is completely lost ( Hoxd12), and the other two ( Hoxa13, Hoxd13) do not participate in the anteroposterior “marking” of the embryo and are used only in the formation of the genital organs.

Numerous cases of independent loss and partial reduction of limbs in squamates may also be associated with the fact that in this order the hind Hox-genes received evolutionary “freedom” atypical for other animals. The effect of purifying selection on them became weaker, which allowed mutations to quickly accumulate.

Posterior expression areas Hox -genes in lizards and snakes. The lizard has two sacral vertebrae in front of the caudal vertebrae.(shown in dark gray) , followed by one vestigial lumbar vertebra(white) , and then come the thoracic vertebrae(gray) . The snake does not have a lumbar region, and instead of sacral ones there are four cloacal vertebrae with bifurcated ribs(dark gray) . Vertical rectangles areas of expression of the posterior Hox -genes. From Di-Poi et al., 2010 .

It is known that the rear Hox-genes play a key role not only in the design of the hind parts of the body, but also in the development of the limbs. Therefore, some mutations of these genes, leading, for example, to elongation of the body or reduction of the lumbar region, can theoretically lead to such side effects as reduction of limbs. Body elongation combined with limb reduction is also found in other groups of vertebrates (for example, in some amphibians). Was this related to the same changes in work? Hox-genes, like those of snakes, or with others, further research will show.

Evolutionary developmental biology is a rapidly developing discipline from which major scientific breakthroughs can be expected. Deciphering the gene regulatory networks that control development is one of the most pressing challenges in biology. Its solution will make it possible to understand not only the relationship between genotype and phenotype, but also the most important rules and patterns of the evolution of complex organisms. When these rules, known to us today only in general terms, are studied in detail, right down to the construction of strict mathematical models, unprecedented opportunities will open up for humanity. Designing biological systems from scratch with the properties we want is just one of them. The other is the improvement of our own nature. All this will happen. You just need to clearly understand for what purposes future humanity needs this, and hope that the cultural, social, moral and ethical development of humanity by that time will eliminate the possibility of using these discoveries for harm.

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Homeotic genes - (regulatory embryonic genes) determine the processes of growth and differentiation of the organism in plants and animals; mutations in them lead to the transformation of some organs into others. (meaning?)

Animal homeotic genes contain a region (homeobox) that is almost the same in all species (180 bp = 60 AA). They are called Hox genes (homeobox-containing genes).

Homeotic genes are located on one or several chromosomes, in close groups (from 4 (comb jellies) to 48 (mammals)), within which a strict order is maintained: “head” genes in front, “tail” genes in the back. Their function is to “turn on” or “turn off” other genes. (meaning – and further underlined) The linear order of genes within a cluster corresponds to the time or place of operation of the gene during embryonic development.

Hox genes were found in all studied organisms (in the genomes of hydras, leeches, nematodes, fish, mammals, amphibians, sponges). These are ancient genes that appeared >1000 million years ago. The increasing complexity of the structure of organisms was accompanied by duplication and divergence of their functions.

Despite the diversity of flower structure, its development is controlled by conserved homeotic genes.

Foliar (classical) theory of flower morphogenesis by I.V. Goethe:

Presentations: A flower is a modified shoot with shortened internodes. Flower organs are transformed leaves. Developed in his works: (1790) “An Experience on the Metamorphosis of Plants”; (1810) “The Doctrine of the Flower.”

According to the classical, or foliar (from Latin folium - leaf) concept, expressed by I.V. Goethe (1790), supported by A.P. Decandolle (1813) and other researchers, all flower elements are metamorphosed leaves. Therefore, a flower was defined as a modified shoot with limited growth, adapted to carry out all the processes that ensure seed propagation of plants.

The triple mutant phenotype provides convincing evidence in favor of Goethe's foliar theory of flower morphogenesis.

ABC model of flower development:

ABC –model – modern paradigm developmental genetics. According to this model, the differentiation of flower organs is determined by the work of 3 classes of regulatory genes: class A genes are responsible for the development of sepals, together with class B genes they determine the formation of petals, the joint work of class B and C genes leads to the development of stamens, and C genes by themselves control the appearance of the pistil in the center of the flower. These genes encode transcription factors that cause specialization of plant tissues during development.

Subsequently, two more classes of genes were added: class D genes, which are responsible for the development of the ovary in a flower; mutations in this gene lead to the development of carpels instead of the ovary, and overexpression of these genes leads to the formation of ovaries instead of sepals and petals; and class E genes that control the identity of the three inner circles.

When these genes are disrupted, some parts of the flower turn into others (stamens into petals or petals into sepals). The model species in these studies was Arabidopsis, in which a number of homeotic mutations were discovered, some of which, when combined, transformed all parts of the flower into leaves.

Since the early 1900s Society of Biologists used a small Drosophila (Drosophila) to conduct thousands of experiments. Students in biology classes work with fruit flies, crossing different varieties to develop patterns of inheritance. Today, there are thousands of publications devoted to fruit flies, and for secular biologists they are a creature that is well suited for the study of evolutionary genetics. This insect is used because it is genetically relatively simple. Drosophila have 4 pairs of easily observable chromosomes containing only 13,000 genes (DNA). IN In March 2000, the entire Drosophila genome (set of genes) was determined.

Radiations such as X-rays, and various frequencies and lengths of X-rays irradiated insects in the laboratory, resulting in the production of, for example, abnormal wings known as "wingless", "vestigial", "drooped", etc. Since 1910, geneticists have recorded more than 3,000 in these creatures, but so far scientific journals there hasn't been a single recorded case of fruit flies evolving into anything else, no matter how much they mutate.

Indeed, the late evolutionist Pierre Grasset argued: "Drosophila (Drosophila melanogaster), the favorite insect of geneticists, whose geographical, biotypic, urban and rural genotypes have now been studied far and wide, has not changed since ancient times.”

Hox genes (specific DNA sequence): no help for macroevolution

When an embryo begins to develop, its body plan unfolds under the direction of control genes, which include a group of genes called homeobox or xox genes. Genebithorax is a part hox genes, which, after mutation, can form a Drosophila with four wings (usually they have two wings). It is said that "in most cases, experimentally induced mutations in homeotic genes produce fundamental changes in [the basic design of the body]" and one non-creationist stated:

“Control genes, such as homeotic genes, can serve as targets for mutations that would possibly change phenotypes, but it must be remembered that the more centrally changes are made in a complex system, the more severe the peripheral consequences. Homeotic changes caused in fruit fly genes lead only to deformity, and most experiments do not expect to see the emergence of a bee from their (fruit fly) design elements."

Decades ago, an example of a “good mutation” was given by a biologist at the University of Denver during a discussion with the author. The mutation involved a gene bithorax, which produces an atypical fruit fly with four wings. Unfortunately, evolutionists did not tell listeners that the fruit fly's ability to fly was severely damaged. What would natural selection do with such mutated creatures?

Links and notes

We are all a little mutants, and each has our own DNA, the only one and - not counting twins and clones - unrepeatable. However, the general public is accustomed to being afraid of mutants, imagining some unfortunate inhabitants of Mars from the movie hit “Total Recall”: with an extra arm, missing ribs or a severely deformed body. Such mutations are also known, and today it is possible to artificially raise flies with legs on their heads or mice with two upper jaws. The main thing is to choose the right target - a small group of very important genes that determine the body structure of animals.

Since one of the founding fathers of modern genetics, Thomas Morgan, began culturing fruit flies in 1906, they have become one of the most studied animals on the planet. Their small size, unpretentiousness, and most importantly, their short life cycle have made Drosophila a popular model for genetic research. By the middle of the 20th century, scientists had seen myriads of flies with the strangest manifestations of mutations, with violet or white eyes, without bristles on their bare bodies... But what Edward Lewis, an employee of the California Institute of Technology, saw in the late 1940s, caught his eye for a long time . The fly had an extra pair of wings, like some butterfly.

The formation of the segmented body of Drosophila begins long before the work of Hox genes - even with messenger RNA, which is introduced into the egg even before fertilization, at the maturation stage. Some of them are concentrated in the front part of the cell, others in the back, so that in the first hours of embryo development, when proteins are actively synthesized on these mRNAs, a gradient of their concentration arises in it: at the anterior pole there is more Bicoid protein, at the rear - Nanos. Different concentrations of proteins trigger different genes of the Gap and Pair-Rule families, which are responsible for the segmentation of the embryo. And only when the segments are sufficiently formed, the homeotic Hox genes, associated with the specialization of the segments, come into play. For their discovery of these mechanisms in 1995, Eric Wieschaus and Christiane Nüsslein-Volhard shared the Nobel Prize in Physiology or Medicine with Edward Lewis.

History of the fly: development

Lewis was not the first to notice such ugliness - and there was something to think about. An animal's body develops from a single cell, and each new generation of cells carries the same initial set of chromosomes and genes (minus the sex cells, which do not appear immediately). In different tissues and parts of the body, slightly different sets of genes are activated - and cells develop according to different scenarios. Some form the Drosophila's legs, others its antennae, and others its wings, obeying the genes that direct their growth. A malfunction of genes can result in serious problems for a fly, for example, the appearance of an additional pair of wings or legs growing between the eyes, in place of the antennae.

Our expert Pavel Elizariev, Jr. Researcher Laboratory for the Regulation of Genetic Processes, Institute of Gene Biology, Russian Academy of Sciences: “It so happens that the complexes of homeotic genes have become one of the most studied in the fruit fly and other organisms - probably, a fly with legs on its head was very remarkable. But over time, the story became even more interesting. When, about 30 years ago, the mutations leading to transformations in the fly’s body began to be precisely mapped, it turned out that none of them were located within the Hox genes themselves. Most affect broad genomic regions around that do not code for anything: sequences that regulate the activity of surrounding genes are located here. These sequences do not work on their own, but by binding to activator proteins or repressor proteins. A whole new level has opened up in the regulation of body structure - and the complexes of homeotic genes have become a testing ground for the study of non-coding DNA, which occupies about 98% of our genome.”

There are many such violations of the correct development of the body in Drosophila. Lewis noted that they were associated with the incorrect formation of an entire segment - as if the third segment of the chest suddenly began to consider itself the second and hastily grew extra wings. The Ubx gene was also found, mutations in which triggered development in the wrong direction. And soon Ubx found relatives - two more genes located on the same third chromosome, next to it. And since they make one segment similar to another, they were called that way, only in Latin, homeotic (Hox).

By the early 1980s, the work of Lewis and other scientists helped identify all the Hox genes, mutations in which make some segments of the fly's body similar to others. There were eight of them, and they formed two close groups. Ubx and two others constitute the Bithorax complex, which is activated in the nine posterior body segments of Drosophila. The five others work in the chest and head segments, forming the Antennapedia complex - the most significant in this group was the Antp gene: by disrupting its work, you can grow legs in place of the head antennas. The most interesting thing was that Hox genes are located in the genome in exactly the same order as their segments in the body - from the head to the tip of the abdomen.


The ancient homeobox fragment is found even in plant genes that act together with genes containing a similar MADS box. Moreover, MADS has been found in almost all eukaryotes studied, including yeast and humans, although the functions are different in each. In plants, all major developmental programs are under their control, so they can be considered analogues of animal Hox genes.

Animal History: Evolution

In 1983, Swiss biologists found an unexpected feature in Drosophila homeotic genes. common feature: they all had a small, only about 180 nucleotides long, but characteristic sequence, a “homeobox”. This amazing fragment encodes a protein domain of about 60 amino acids that binds to DNA and is found in virtually all animals, from sea stars to stage stars. The order of arrangement of Hox genes on the chromosome is preserved with almost the same strictness in animals. Such conservatism speaks of the important role played by Hox genes and their dizzying antiquity.


The small changes in the homeobox that distinguish one group of animals from another have made it possible to trace their possible history back to a common ancestor, which most likely had a core group of four Hox genes. Coelenterates do not need such complexity, and they have lost half of them. But already in the ancestor of bilateral animals, who lived about 600 million years ago, they doubled, and each took on its own functions, slightly different from the others. Such complications occurred several times, so that if Drosophila and other insects have eight such genes, then the chordate lancelet has 14. Hox genes reached their maximum number in vertebrate tetrapods - amphibians, reptiles, birds and mammals. This complex of genes exists in four of us. similar friends copies on each other, so that even with a few losses, their total number exceeded 30. In fact, although the segmentation of our body from the outside is not as noticeable as in worms or insects, it exists, and Hox genes determine whether the vertebrae will connect with ribs or even fuse into the tailbone. A mutation in Hox10 in mice causes them to grow ribs even on their stomachs.


The Lizard's Story: Regeneration

Several years ago, St. Petersburg biologists studied the work of the Hox genes of the Nereis annelid worm in the larval and adult states. It turned out that while in the larva their work follows the classical scheme familiar from flies, in the adult worm it dramatically changes the program. Instead of each Hox gene being activated in its own segment, they are turned on everywhere and differ only in the degree of activity. It is assumed that this allows Nereis, which has lost its tail segments, to safely grow new ones.


Human embryonic development is an incredibly complex process. Therefore, disturbances in the functioning of Hox genes, as a rule, result in miscarriages in the early stages of pregnancy. However, occasionally children are still born - one of the results of mutations in Hox clusters may be Goldenhar syndrome (hemifacial microsomia). This is a severe disease that is associated with multiple developmental defects and, of course, remains incurable. There are also indications of the possible role of Hox genes in the development of certain types of cancer, such as leukemia or breast cancer. Usually almost silent in the adult, some of the Hox genes can become active again in tumor cells, “waking up” under the influence of signaling molecules and growth hormones.

This picture is not at all new, even for much more complex vertebrates. Many reptiles and amphibians, known for their ability to regenerate lost tails and even limbs, use the same homeotic genes to do this. The details of this mechanism are still poorly understood, but it is known that even almost identical, duplicated Hox clusters in salamanders carry different introns - non-coding insertions inside genes that provide greater opportunities for regulation of their activity. Perhaps such “improvements” play an important role in the operation of Hox genes during limb regeneration. In general, despite minor differences, Hox genes are extremely conserved and remain very similar even in such distant groups of animals as insects and mammals. By replacing one of them from Drosophila with a homologous one taken from a mouse, you can grow a completely normal fly. They are even more similar in humans and reptiles.


And if, thanks to them, lizards are able, without blinking an eye, to grow a new tail instead of a bitten one, then will the precise regulation of Hox genes help people? Research in this direction is already underway, and if one day a person is restored to a lost finger or even a whole hand, it is worth remembering that it all began with the story of flies with legs on their heads.