Since their discovery in 1984, homeobox-containing genes have attracted attention molecular biologists, biochemists, geneticists, embryologists and evolutionary biologists. This widespread interest reflects the fact that the homeobox genes represent the first apparent link between all of the above areas.

Homeobox-containing genes are identified by the presence of a characteristic 183 bp DNA sequence (homeobox) encoding a relatively conserved 61 a.a. (homeodomain). It is important to understand that homeodomain sequences are far from constancy; thus, the procedure for determining a homeodomain within an amino acid sequence is not always straightforward. Typically, homeodomains are identified by the presence of three potential alpha helical regions, several invariant amino acid residues, and high level homology with previously characterized homeodomains. The remaining variable regions are two potential alpha helices in the C-terminal region of the domain, which are thought to be responsible for DNA binding specificity and subsequent regulation of target genes. Mammals have four clusters of homeobox-containing genes.

HOX clusters are a highly conserved group of genes evolutionarily related to Drosophila Antennapedia-like HOX genes and Bithorax complexes. Detailed Analysis gene expression patterns of members of all four HOX clusters showed that gene expression domains are spatially restricted in various areas embryo. An important feature of these homeobox complexes is linear correlation between the position of a gene in the HOX cluster and its relative anteroposterior or axial expression domain in many embryonic tissues. This property is called collinearity and is conserved in arthropods and vertebrates; this suggests that the regulatory mechanism for controlling spatially restricted domains of HOX expression is important point in the organization of clusters of these genes. It is believed that the HOX genes are involved in the determination of the spatial organization of the embryo through a specific combination of genes (HOX code) expressed at all levels. This theory is supported by the experimental phenotypes resulting from the targeted disruption of the expression of these genes in vertebrate embryos.

The conservatism in expression and regulation suggests that the signals used to establish and maintain the expression of HOX patterns may also be conserved. After receiving some experimental data, research has focused on possible links between retinoic acid (RA, RA) and HOX genes. Many in vitro studies have shown that HOX genes are regulated by induction of cell differentiation by retinoic acid. In embryos, RK can affect both limb bud patterning and HOX expression patterns in limbs. In a number of vertebrates, the action of RK leads to abnormal growth, differentiation and patterning of the nervous system, neural crest cells and gill arches, which in some cases can correlate with changes in HOX expression.

Thus, the response of HOX genes to RA in cells of cultures and embryos, the presence of RA that binds to embryonic proteins and receptors, and the phenotypic relationships between RA and HOX expression suggest that HOX genes may be targets of regulation generated by RK signaling pathways.

Transcription factor mutations are particularly predisposing to multiple malformations, as these regulatory genes are expressed in a variety of tissues (

Since the early 1900s the Society of Biologists used a small Drosophila (Drosophila) for thousands of experiments. Students in biology classes work with fruit flies, crossing different varieties to develop models of heredity. To date, there are thousands of publications devoted to Drosophila, and for secular biologists, this is the 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 observed chromosomes containing only 13,000 genes (DNA). V In March 2000, the entire Drosophila genome (a set of genes) was identified.

Radiations, such as X-rays, and different frequencies and lengths x-rays irradiated insects in the laboratory, resulting in, for example, wing anomalies known as "wingless", "rudimentary", "drooped", etc. Since 1910, geneticists have recorded more than 3,000 in these creatures, but so far scientific journals have not recorded a single case of Drosophila evolving into anything else, no matter how much they mutated.

Indeed, the late evolutionist Pierre Grasset argued: “Drosophila (Drosophila melanogaster), the favorite insect of geneticists, whose geographical, biotypic, urban and rural genotypes are now studied up and down, has not changed since ancient times.

Hawks genes (specific DNA sequence): no help from macroevolution

As an embryo begins to develop, its body plan unfolds under the guidance of control genes, including a group of genes called homeobox or hawks genes. Genebithorax is a part ox genes, which, when mutated, can form a four-winged fruit fly (they usually have two wings). It is said that "in most cases, experimentally induced mutations in homeotic genes produce fundamental changes in [basic body design]", and one non-creationist stated:

“Control genes, such as homeotic genes, can be the target of 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 the genes of fruit flies only lead to deformity, and most experiments do not expect to see the emergence of bees from their (Drosophila) building blocks.

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 the atypical four-winged Drosophila. Unfortunately, the evolutionists didn't tell the listeners that Drosophila's ability to fly was badly damaged. To do natural selection with such mutated creatures?

Links and notes

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?)

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

Homeotic genes are located on one or more chromosomes, in close groups (from 4 (comtenophores) to 48 (mammals)), within which a strict order is preserved: the “head” genes are in front, the “tail” ones are behind. 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 the gene's operation during embryonic development.

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

Despite the diversity of the 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. The organs of the flower are the transformed leaves. Developed in the works: (1790) "Experience on the metamorphosis of plants"; (1810) "Teaching about the flower".

According to the classical, or foliar (from lat. folium - leaf) concept, expressed by I.V. Goethe (1790), supported by A.P. Decandoll (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 is convincing evidence in favor of Goethe's foliar theory of flower morphogenesis.

ABC model of flower development:

ABC-model is a modern paradigm of 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, teamwork class B and C genes lead to the development of stamens, and the C genes themselves control the appearance of the pistil in the center of the flower. These genes code for transcription factors that cause plant tissue specialization during development.

Subsequently, two more classes of genes were added: class D genes, which are responsible for the development of the ovary in the 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, which 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 found, with the combined action of some of which all parts of the flower turned into leaves.

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

Hox genes got free - and snakes lost their legs

Hox- genes gained freedom - and snakes lost their legs

Finally, consider a study that sheds light on the role Hox-genes in the evolution of vertebrates. As you know, the most important function Hox-genes lies in the fact that they mark the embryo in detail along the anterior-posterior axis. Further fate embryonic cells that ended up in one or another part of the embryo depends on the set Hox genes expressed in this part. For everybody Hox-gene is characterized by its own region of expression. For example, genes Hox12 and Hox13, as a rule, work only in the back of the embryo, which will later become the tail; genes Hox10 in some vertebrates, they work from the rear end of the embryo to the line that will become the border between the thoracic region (where there are ribs on the vertebrae) and the lumbar region, where the ribs do not develop. " Hox-code", which determines the plan of the body's structure, is complex and not quite the same in different groups of vertebrates. There can hardly be any doubt that many of the major evolutionary changes affecting the body plan have been 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 The genes are listed 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 genome-wide duplications). Clusters A, B, C, D are located on different chromosomes (in mice, these are chromosomes No. 6, 11, 15, and 2; in humans, they are Nos. y, 17, 2, 12). Snakes, unlike mice and humans, lack the 12th gene in cluster D ( Hoxd12 ). In the images of a fly and a human embryo, the regions of expression of the corresponding genes are colored in the same colors as the genes themselves. According to recent data, the correspondence between Hox -genes of arthropods and vertebrates are somewhat less unambiguous than shown in this scheme.

In many animals, including vertebrates, Hox-genes in the genome are located in clusters, i.e., groups close to each other. Most surprisingly, the order of the genes in Hox-clusters often (though not always) coincides with the distribution of expression regions along the anterior-posterior axis: the “head” genes are in front, followed by the genes responsible for the formation of the middle parts of the body, and the cluster is closed by the “back” genes that control the development of the rear body parts. Apparently, this is due to the way the 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 one. Therefore, at the anterior end of the body, only the anterior Hox-genes, and the closer to the tail, the more rear genes are included in the work. A convenient way to regulate the 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. On the early stages Vertebrate evolution has seen two genome-wide duplications. As a result, vertebrates acquired four Hox-cluster instead of one. This opened up great evolutionary possibilities for vertebrates (see Chapter 5). Separate Hox-genes in some clusters were lost, but in general their set and arrangement 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 fine-tune embryonic development and facilitated the development of new building plans.

Biologists from Switzerland, New Zealand and the US studied the work Hox-genes in scaly reptiles (order Squamata) (DiPoi et al., 2010). This detachment, which unites lizards and snakes, is interesting for the variety of body plans and the variability of characters associated with the anterior-posterior differentiation of the body (the relative length of body parts, the number of vertebrae in them, etc.). Therefore, it was logical to assume that Hox- clusters of squamates should have specific features and that Hox-the genes of lizards and snakes must be different.

Previously, it was shown that the expression regions 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 arrangement of genes in the cluster and their areas of expression in the embryo) is strictly observed in snakes.

The researchers focused on the rear Hox-genes (from the 10th to the 13th). The main objects of the study were the whip-tailed lizard Aspidoscelis uniparens and maize snake Elaphe guttata. In addition, they were sequenced Hox- clusters of several other lizards, tuatara and turtles. 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 snakes and frogs "lost" the gene Hoхd12(12th Hox- gene from the cluster D). Important changes were found in regulatory regions Hox-clusters. It turned out that all scaly reptiles have lost the regulatory region between the genes Hoхd13 and Evх2, and in addition, snakes have lost a conservative non-coding element between Hoхd12 and Hoхd13 and some regulatory sites in others Hox-clusters. An unexpected result was the presence in Hox-clusters of squamous sets of embedded mobile genetic elements. As a result, the overall length of the back Hox-clusters in squamates has 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 back part have 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 also 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 accidentally, due to the weakening of purifying selection, while others were fixed under the influence of positive selection, that is, they were useful.

The study of the nature of the expression of the posterior Hox-genes in lizard and snake embryos confirmed the assumption that changes in the body plan in the evolution of squamates were closely associated with changes in the work of the hind Hox-genes.

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

Expression area Hoxa10 and Hoxc10 in the snake goes far into the thoracic region. These genes are also responsible for the timely cessation of the growth of the thoracic region. Apparently, their function in snakes is also weakened, which could be one of the reasons for the elongation of the thoracic region in snakes compared to their ancestors - lizards. The lengthening of the tail section 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 anterior-posterior "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 can also be associated with the fact that in this order the posterior Hox-genes received evolutionary "freedom" atypical for other animals. Purifying selection became less effective on them, which made it possible to quickly accumulate mutations.

Regions of expression in the posterior Hox -genes in lizards and snakes. The lizard has two sacral vertebrae in front of the tail vertebrae.(shown in dark grey) , followed by one vestigial lumbar vertebra(White) , and then go the thoracic vertebrae(gray) . The snake does not have a lumbar region, and instead of sacral vertebrae, there are four cloacal vertebrae with forked ribs(dark grey) . vertical rectangles shows the areas of expression of the posterior Hox -genes. From DiPoi et al., 2010 .

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

Evolutionary developmental biology is a rapidly developing discipline from which major scientific breakthroughs are to be expected. Deciphering the gene-regulatory networks that control development is one of the most urgent tasks of biology. Its solution will make it possible to understand not only the relationship between the genotype and phenotype, but also the most important rules and patterns of evolution of complex organisms. When these rules, known to us today only in general terms, are thoroughly studied, up to the construction of rigorous mathematical models, unprecedented opportunities will open up before humanity. Design from scratch biological systems with the properties we need is just one of them. The other is the perfection of our own nature. All this will be. It is only necessary to clearly understand the purposes for which future mankind needs it, and to hope that the cultural, social, moral and ethical development of mankind by that time will exclude the possibility of using these discoveries to the detriment.

Sea snakes About 350 million years ago, the coelacanth's air-breathing relative, the coelacanth, climbed out of the water on its clumsy cross-finned fins and became the first vertebrate to live on land. Plants and invertebrates have already managed to spread there, penetrating from