The history of generation of mutations in ontogenes commenced from the idea to partition the biological traits by distinguishing between the traits of intraspecific similarity and those of intraspecific differences. The former are inherent in each individual of a species, determine the outlook of the species, and distinguish it from the other species. The latter are present in some representatives of a species but are absent in the others. The Mendelian protein-coding genes fit the role of the latter 111232.

We constructed the “genetic portrait” of the genes responsible for the buildup of the characters that determine the intraspecific similarity. The mutations in these genes seem rather paradoxical: they have to be viable in homozygote and lethal in heterozygote (dominant lethals) 111232. New hybridization techniques allowed us to isolate the target mutations in different chromosomes and in large amounts from the irradiated D. melanogaster individuals 6733. The collection of mutations became the source of vast and unusual information about the new category of genes 89. Some mutation manifestations gave us the idea about the feasibility of building up a logical construction referred to as the model of speciation. Find below the description of these manifestations and the logic used for the construction of this model named the regeneration model of speciation.

Table 1 lists the progenies of the drosophila males carrying the generated mutations in their X chromosome. The viable mutant males in the crosses with yellow females do not produce daughters, that is, the mutation in daughters acts as a dominant lethal although it manifests no lethality in the male genome of the fathers. Table 2 shows the results of crosses of the same mutant males with the females differing form the females used in the first set of crosses by the presence of the In(1) Muller-5, w^aB inversion in one of the X chromosomes. This inversion emerged to be sufficient for the mutation to lose its dominant lethality in daughters. Both classes of daughters (+ and B/+) appeared in the progeny. Thus, these mutations in the X chromosome manifest themselves as dominant lethals only when the mutant paternal X chromosomes meet with the X chromosomes of yellow females. The presence of the X inversion in a female is sufficient for the mutation to lose its dominant lethal effect.

The elimination of a lethal effect of the mutations in the test cross with yellow strain repeats if the mutant males are crossed with females (1)In (1)5, y/y, (2) In (1)23, y/y, (3) T (1; 2)12 y/y, and(4) T (1; 2)19, y/y, carrying chromosomal rearrangements in the yellow strain or females of other (wild type) strains Berlin wild and Barnaul11. The lethal effect of these mutations is also eliminated in the case when female crossed with a mutant male carries the chromosomal rearrangements not in the X chromosome but in the chromosomes of the second and third pairs (females y/y; +/Cy, females y/y; +/Pm and females y/y; +/D) 8.

Not only mutations in the X chromosome, but also mutations in other chromosomes manifest themselves as a “facultative dominant lethal”. The ability of a mutation to cause lethality under certain genotypic conditions and to fail to manifest it under other conditions has allowed us to design different techniques for generating facultative dominant lethals, including the mutations in chromosomes 2 and 3. Table 3 shows the progeny of facultative dominant lethals in drosophila chromosome 2. Characteristic of the lethals of this type is that they manifest dominant lethality in the compound with a structurally normal autosome 2 but do not manifest it if the opposite chromosome carries the 2 In(2LR) SM1 inversion 33.

The facultative dominant lethals represent the class of mutations the genetics encountered for the first time. By definition, any individual carrying a dominant lethal cannot exist at all. The facts that the mutations with the features of a dominant lethal are obtained and do exist as stocks is explainable by a facultative character of their dominant lethality. In certain genetic surroundings (ensemble), a mutant ontogene manifests itself as a dominant lethal and the corresponding individual dies in heterozygote; however, it survives, exists in full, and gives progeny in other surroundings. Some genetic conditions that abolish a lethal behavior of the ontogene, such as chromosomal rearrangement and sex of mutant, are shown above. The overall experimental work with the mutations in ontogenes has been performed with the stocks in which the dominant lethality is removed using a particular technique.

The specific functional features of ontogenes able to form facultative dominant lethals are briefed in Table 4 versus the function of a Mendelian protein-coding gene. They are structurally similar since both are represented by DNA regions but are functionally distinct. Being changed (mutated), Mendelian gene creates a single mutant variant, whereas ontogene creates two variants. One of the latter is a lethal (a step towards isolation) and the other variant represents a retained mutation capable of further alterations. Thus, it is clear that ontogene, even in formal terms, has more opportunities to influence evolution. These opportunities are considered in detail below.

Characteristic of the facultative dominant mutations is a parental pattern of inheritance. In the crosses of the males carrying a mutation in the X chromosome with yellow females (Table 1), not only the absence of daughters in the progeny attracts attention, but also a high level of undeveloped eggs. In the case all daughters die, this level must not exceed 50%; however, it was considerably higher for the majority of mutations. This reasonably suggests that not only daughters, but also sons were among the lethals. The latter have not received the mutation from their father but nonetheless died. The transfer of a trait from father to its progeny without the transfer of the corresponding mutation is a manifestation of the parental effect.

The interaction between mutations and chromosomal rearrangements (Table 5) follows a typical parental pattern of inheritance. The progeny of mutant males crossed with yellow females lacks daughters, which appear if the mother females carry inversions in autosomes: In(2LR)Cy, In(2LR)Pm. or In(3LR)D. Thus, the inversion in mother’s genome partially eliminates the lethal effect of mutation. Interestingly, the presence of inversion in the survived zygote is not obligatory for the removal of lethality. Survived zygotes have either phenotype Cy (containing the inversion of mother) or phenotype Cy+ (lacking the inversion of mother), as well as Pm and Pm+. Obviously, here is a typical parental (in this case, female) effect of chromosomal inversion in chromosome 2 on the manifestation of mutation received by daughter from its father.

Of interest is another form of the parental effect observable in the case of interaction between the rearrangements in autosomes and mutations in the X chromosome 32 (Table 6). In this experiment, males carried both rearrangements and mutations. In this combination, the rearrangements failed to cause the effect. The males crossed with yellow females gave no daughters in their progeny although the mutations in the zygote were present together with the studied chromosomal rearrangement In(2LR)Cy (Table 6). Thus, the removal of lethal mutation manifestation by the rearrangement depends on the particular parent from which it was received as well.

As of today, the complete list of manifestations of the mutations in ontogenes comprises seven variants: (1) facultative dominant lethality; (2) facultative recessive lethality; (3) dominant effect on metabolism and activity; (4) dominant effect on meiosis; (5) dominant generation of morphoses; (6) dominant generation of instability; and (7) dominant type of modification of ontogene manifestations (rearrangements in heterozygote). The parental pattern of inheritance in different variants is characteristic of all seven manifestations 3134353637 although only three cases, associated with manifestations (1) and (7), are described above for the sake of brevity.

A parental pattern of inheritance is a consequence of the gene activity in a germinal cell. The initial mutation and the “product of its activity” during the reduction division in meiosis are distributed independently of one another to give the gametes carrying the “product of activity” but lacking the mutation that is its source. In terms of phenomenology, the formation of the gametes of this type gives the progenies that received the parental character without receiving the correspondingly gene (parental pattern of inheritance) 35. The parental pattern of inheritance of mutant manifestations in an ontogene suggests that (1) ontogenes are active in germline cells, (2) they interact with other ontogenes, and (3) the interaction leaves a “trails”, which are delivered together with the gamete. Numerous cases of paternal parental effect (in particular, shown in Table 1) that exclude the transfer of the cytoplasm components of the sperm to the zygote suggest that the parental effect of an ontogene is determined by the changes in the conformation of other ontogenes.

The observations of mutations in ontogenes in permissive stocks have supplied us with extensive information about the specific features in mutation manifestations. One of the key specific features of mutants is their physiological and genetic instability. Find below six arguments favoring this inference.

Development of morphoses, modifications, mosaics, and gynandromorphs. Many mutations have been found to give rise to phenotypically abnormal progeny. Generally, these abnormalities are morphoses affecting various body parts; they are mainly asymmetric and uninheritable. Both the maternal and paternal effects are observable in the development of morphoses. In four cases, dimorphic mutations are recorded, namely, a female homozygous for a mutation had a mutant phenotype, while its male counterpart was phenotypically normal. The mutations are recessive with regard to the norm. New phenotypes behaving as mutations with incomplete penetrance emerged during cultivation. In the stocks of mutant homozygotes, numerous phenocopies emerge, persist for one or two generations, and disappear. One wave of phenocopies followed the other. The emerging visible phenotypes further behave as ordinary recessive mutations 383940.

Loss in manifestation of a dominant mutation in the opposite chromosome. Characteristic of the lethal mutations in autosome 2, maintained in heterozygote with inverted chromosome In(2LR)Cy, CyBlL4, is the “loss” in manifestation of dominant mutations Cy , Bl, and L4 in the inverted chromosome (Figure 1). The loss takes place in the crosses aimed at maintenance of mutations and in the crosses between mutant stocks 8. Over the first half year of mutation maintenance, 20 cases of the loss in manifestation were recorded (Figure 1): one marker was lost in 17 cases and two markers (Cy, Bl, and L4 individuals) in three cases. The reciprocal classes sharply differ in the abundance, suggesting that the nature of the losses is not related to crossing over. The chromosomes with the altered set of dominant markers continue acting as the balancers of lethals in autosome 2. This is another argument against a crossing-over nature of the losses. The loss in dominance manifestation for each of the three mutations was autonomous. That is why the loss in one mutation was the most frequent and in two, less often. Any case of the loss in all three mutations was unobservable. Each of the mutations was lost separately but at different rates. The Curly mutation was lost in 11 cases; Lobe, in 10; and Bristle, in two cases.

The rate of loss in manifestation was high. Six cases of nonmanifestation among 90 progenies (rate, 6.7%) were recorded in the crosses of two lethal stocks (nos. 37 and 53). However, any case of the loss in marker was unobservable among 833 progenies in the cross of yellow females with mutant males (four stocks). Over several decades when the In(2LR)Cy, Cy Bl L4 chromosome was retained in laboratory stocks, any cases of the loss in manifestation of dominant markers have not been recorded. Correspondingly, we believe that mutations in ontogenes were the actual reason underlying the loss in dominant mutations in the In(2LR)Cy, Cy Bl L4 inverted chromosome.

Lethal mutations l(2) in autosome 2 were maintained in the stock with the inverted autosome 2 carrying dominant mutations Curly (Cy), Bristle (Bl), and Lobe (L4). In the norm, the progenies manifested all three dominant mutations; however, the loss in manifestation of one or two mutations was observed in 20 cases.

Secondary mutagenesis. The lethals were mapped using a standard set of deletions for 10 mutations in ontogenes displaying a recessive lethality in chromosome 2. Five mutations had two and more lethal defects. The multiple lethal defects of an individual mutation are unexplainable with the statistics of γ-irradiation. One of the mutations with four lethal regions had a small barrel (Smba) visible phenotype. The Smba phenotype in the Smba/In(2LR)Cy strain is inherited according to the parental pattern but disappears in the Smba/In(2LR)Pm strain. In the same strain, lethality is lost in one of the four initially lethal regions. In a separate experiment, we observed how the mentioned region commenced to lose the lethal manifestation after introducing the In(2LR)Pm chromosome into the Smba/In(2LR)Cy strain. We also observed the process of loss in Smba phenotype in three substocks of the Smba/In(2LR)Cy stock after its cross with the Smba/In(2LR)Pm strain over 13 successive generations. In our view, the regions of multiple recessive lethality repeatedly (secondarily) emerge under the influence of a radiation-induced mutation in ontogene 41.

Transposition of mobile element 412. This study involved two strains carrying mutations in ontogenes in the X chromosome. The strains were dimorphic: only females displayed the mutant phenotype, whereas the males were normal. Multiple transpositions of retrotransposon 412 were observed in the strains. The rates of inversions exceeded those for isogenization, a strong inducer of MGE (mobile genetic element) transposition 42.

Disturbances of meiosis and mitosis. In total, 30 mutations in ontogenes located in the D. melanogaster X chromosome were assayed for their ability to cause the meiotic nondisjunction of X chromosomes 31. The level of X nondisjunction in the females heterozygous for mutation in ontogene emerged to be very high. The share of matroclinous daughters reached 24.7% of the total progeny and of patroclinous males, 24.9%. An inversion in the opposite X chromosome and additional Y chromosome had no effect on the X nondisjunction. The balance between XX and X0 egg cells was disturbed: exclusively daughters were prevalent in the females with a normal opposite X chromosome versus the females with inverted X chromosome, displaying the prevalence of sons. Moreover, 12% of the matroclinous daughters produced by the mothers with a normal opposite X chromosome appeared to be homozygous for the marker of one of the maternal X chromosomes (equational nondisjunction). A “damping” parental effect of a mutation in ontogene on the X chromosome nondisjunction was observed 31.

Increase in basal metabolism and locomotor activity of mutants. An unusually high mobility and a high sexual activity of mutant males were recorded. The energy metabolism of mutants was assessed using special tests. For this purpose, it was measured in the flies of four mutant and four control strains with indirect calorimetry (according to the emitted CO₂). In addition, a special device was used to assess the locomotor activity of these flies. The energy metabolism and locomotor activity of the mutants were higher as compared with the control in a statistically significant manner 8943.

The above data demonstrate a physiological and genetic instability caused by the presence of a mutation in ontogene. Section 1.5 will consider the data on the changes in the lethality of mutations over their cultivation in laboratory. They supplement the body of the data on the instability in mutant stocks.

In the genetic experiments with drosophila, the death of a few laid eggs does not attract any attention. This can be caused by failed fertilization or a chromosomal rearrangement received by a progeny, which disrupted its viability. The following facts were observed in the crosses of mutants for ontogenes: (1) a very high level of egg death (Table 1) (2) for the overwhelming majority of mutations (3) in heterozygous state. Undoubtedly, we encountered an outstanding phenomenon determined by the specificity of mutations. In the experiment with yellow females, we determined the critical phase in lethality for 18 mutations in the X chromosome (Table 7). This experiment allowed us to assess the death rate at the stages of (1) white egg, (2) brown egg, (3) larva, (4) pupa, and (5) imago. The egg samples were obtained from assuredly fertilized females. The death took place at the stage of egg in 90% of the cases (72%, at the stage of white egg and 18%, brown egg). The stage of white egg matches the zygote containing two pronuclei to syngamy and of brown egg, the first stages of embryonic development after syngamy. Thus, the disturbance of the events taking place immediately before the syngamy kills the mutants 363744. The details of this phenomenon are described when discussing it in Section 2 “Critical events of speciation performed by mutant ontogenes”.

Processing of lethal mutation manifestation in generations of permissive stocks. The instability of permissive stocks, mentioned in Section 1.4, had one more specific feature, namely, it changed with time. In particular, the rate of the individuals with monstrosities decreased with the duration of stock cultivation. A change in the cross mate again increase the yield of monstrosities; however, the trend of a decrease yet retains. The other mutation manifestations underwent changes as well. We succeeded in recording the changes with time for some of them.

Loss in dominant lethal with time (delethalization). The loss in a dominant lethal effect of mutations was accidentally discovered in 2001 in the experiments on determining the rate of dominant lethals. The males from stocks nos. 1, 3, 5, 27, and 33, maintained using the attached X chromosomes, commenced to give daughters in the crosses with yellow females (Table 1). In the following years, the lethality was tested using more representative samples of progenies. Five of the above-mentioned mutations, tested in 2002 and 2004, demonstrated that they actually lost their lethality. In 2002, three additional mutations (nos. 29, 38, and 41) lost their lethal effect and one more (no. 35), in 2004. Lethality did not disappear but decreased in some stocks so that daughters appeared in the progeny although their share did not reach the expected level of 50% (nos. 7 and 9–11). In total, nine of the 23 mutations completely lost their lethality and four turned semilethal 1718.

The delethalization of mutations nos. 1–41 took place in the stocks maintained in heterozygote with the Muller-5 chromosome. Over the same time interval, eight mutations (nos. 3, 5, 9–11, 32, 34, and 38) completely lost their lethality and eight mutations (nos. 6–8, 30, 31, 33, 35, and 36) decreased it. The difference in the techniques used for maintaining mutations definitely influenced delethalization. The Muller-5 stock preserved mutations more reliably. After the loss in lethality and its sharp decrease in some stocks were discovered in 2002, ten stocks maintained using attached X chromosomes were duplicated by new stocks obtained from the males of the corresponding Muller-5 stocks, which retained the lethality of mutations. By 2004, seven mutations of the ten, that time maintained using attached X chromosomes, once again lost their lethality. Only three of them retained the lethality in both cases, including the maintenance using the Muller-5 chromosomes. These data suggest that the properties of mutations did change in stocks. This process depends on both the mutation itself and its genome surroundings 1718.

Loss in recessive lethality (homozygotization of mutation). In the previous section, we referred to the loss in a dominant lethal manifestation by a mutation in the cross of mutant male and yellow female as delethalization. This cross repeats the test cross for detection of mutations. The occurred delethalization refers only to dominant lethality, while recessive lethal manifestation of mutation remains. However, the cases of the loss in this type of lethality appeared in the further maintenance of the X-chromosome mutations in the +/In(1) Muller-5, B,w^a. They were easily recognizable according to the emergence of +/+ females. The first +/+ females were completely sterile,; with time, weakly fertile females started to appear as well. Thus, we can assert that a lethal manifestation of mutations is lost with time (thereby restoring fertility). This process develops in a stepwise manner: (1) first, only facultative dominant lethality disappears (2) followed by weakening of recessive lethality with emergence of homozygotes for mutation, and, finally, (3) sterility disappears in the homozygotes for mutation so that they become fertile. Unfortunately, the phenomenon of the loss in lethality is rather infrequent and we have no adequate statistics for this phenomenon. This process is of a fundamental importance and will be discussed in the next sections.

The synthesis of evolutionary theory in one of its variants specified the following factors of evolution: (1) mutation process; (2) isolation; (3) natural selection; and (4) population waves 2. The mutation in gene is regarded as the elementary structure of evolution. The pattern of manifestation of ontogenes described in the previous section comprises many episodes that the synthesis of evolutionary theory ascribed to speciation, in particular, the induction of mutagenesis caused by a primary mutation, zygotic selection in the form of the eggs with arrested development, and emergence of morphological novelties in the form of morphoses. As is mentioned above, once the mutations in Mendelian genes are unable to implement the processes that the synthetic theory states necessary for speciation 5, the ontogenes, as is suggested by the manifestation of their mutations, can well turn out the appropriate but missing tool for implementation of the tasks related to speciation. Three of the processes suggested by the synthetic theory to lead to speciation are key factors: selection, mutagenesis, and isolation. See below that all these three processes can be performed by ontogenes. Table 8

Darwinian natural selection goes on under the action of environment among the adult sexually mature breeder organisms. The selection among the mutants for ontogenes also takes place but at the stage of zygote. At this stage of individual development, it is out of question to speak about the effect of environment because the multicellular organism as such does not yet exist. Zygotic selection is a pure autogenesis (nomogenesis or orthogenesis as synonyms) organized and controlled by the genetic system itself. The evolution of the living beings in this case is inspired by the living itself and its tool is the genetic system of the living.

The methodology of the zygotic selection is more intricate. The selection according to Darwin is the summation of mutations in the generations and each of mutations contributes to an increase in fitness. The summation does not alter the quality of the selected material but changes its quantity. Zygotic selection operates with facultative dominant lethals. In this process, not the primary mutations are the object of selection but rather genetic supplements to them that protects the mutation against elimination. In the former case, the supplement discards dominant lethality and in the other, does not discard it. In the former case, zygotic selection allows a mutation in ontogene together with the supplement to continue its life, eventually giving rise to the adult progeny carrying the mutation in ontogene in a permissive genotype. In the latter case, the life process is arrested, resulting in a fertilized white egg that ceased to develop.

The final biological effects caused by selection are vague. Unlike Darwinian selection, zygotic selection does not specify the direction of further evolution. It only gives a chance to continue existence of a mutation in an ontogene. The direction will be specified by the trends that exist in the living and thanks to which it emerged. They are currently unknown; however, the results of the relevant experiments define the address where the preserved mutation in ontogene will reside and where the next round of evolutionary events can occur. This address is the germline cells of the progeny carrying the mutation in ontogene within a permissive genotype.

Table 5 lists the results of an experiment on the effect of chromosomal rearrangements in the mother’s genome on the manifestation of the mutation in ontogene delivered from father. In the absence of rearrangement in mother, the mutation in ontogene kills all female progenies (column 2 shows the absence of daughters in cross). Chromosomal inversions In(2LR)Cy,In(2LR)Pm, and In(3LR)D in mother partially eliminate the dominant lethal effect of the mutation in ontogene so that daughters commence to appear in progeny (columns 4–5, 8–9, and 12–13). Noteworthy that the survived daughters contain not only the individuals with the Cy, Pm, and D inversions, but also those lacking these inversions. The observed effect of inversions can be validly regarded as a parental effect suggesting that the effect of inversions took place in the maternal germline cells during egg maturation. This experiment, as well as the others that demonstrate the parental effects in mutants, indicates that the most important events of an evolutionary scale are associated with the activity of ontogenes in germline cells.

The assertion that evolution is the process going on with the help of gene mutations prompts the idea that some mutations induce other mutations. This induction would allow a mutation to generate a set of mutations and, eventually, a new characteristic based on this set. However, geneticists have been constantly disappointed on this way. Any signs of chain mutagenesis have been undetectable. It is clear now that the absence of any induction of mutagenesis lies in the specificity of Mendelian genes. Usually, mutagenesis is tested according to the emergence of mutations in the parental germline. The Mendelian protein-coding genes are inactive, in the germline cells, making it senseless to expect an activation of mutagenesis there. The work with mutations in ontogenes immediately demonstrated the activity of this gene type in germline cells (parental effects) and the mutants in ontogenes displayed a very high rate of mutagenesis. Secondary mutations, morphoses, loss of dominant mutations, transposition of mobile level, and processing of lethality evidently confirm this. The epithet “explosive” 4546 precisely characterizes the mutagenesis observed in the mutants for ontogenes. It is not improbable that an increase in the basal metabolism in the mutants for ontogenes 91443 is associated with the mutagenesis that continues in the soma.

The isolation between two groups of organisms appears as the unfeasibility to have common progeny on the background of the fact that the production of progenies within each group is not disturbed. The relevant experiments show that a mutation in an ontogene is the first step in the formation of a genetic isolate. Once a mutation is formed in an ontogene, a single united panmictic population falls into two parts. The first part consists of the individuals lacking the mutation (say, nonmutant subpopulation). It is a continuation of the initial one and develops without any problems via panmictic reproduction. The second one consists of the progenies of the mutant for ontogene, which carry the mutation (correspondingly, mutant subpopulation).

The mutant subpopulation is partially isolated from the nonmutant subpopulation. This isolation appears as the death of part of common progeny of two subpopulations at the stage of zygote. However, the mutant subpopulation does not cease existing: part of the mutations survives by utilizing the suppressors of dominant lethality available in the initial population. Moreover, the mutant subpopulation commences to change because of the resulting genetic instability, which is induced by the presence of the mutation in ontogene. In the subsequent crosses of the representatives of both subpopulations, the composition of suppressors of dominant lethality can change qualitatively and quantitatively depending on the genetic variants emerging as a result of this genetic instability. The mutant individuals can be with good reason regarded as a mutant isolate. They become the scene of a set of genetic alterations, which eventually can lead to a complete genetic incompatibility with the nonmutant part of population.

The phenomenon of mutation emergence in a Mendelian gene and its further fate in population have been considered in many papers on population genetics; however, the authors have not seen any reasons to regard the mutations in Mendelian genes as the cause of further isolation. This feature appeared in ontogenes and stems from their unique function, namely, the ability to organize the process of ontogenesis. The ability to form chains of genes is unalienable from the ability to break these chains. The ability to organize a control system simultaneously means the ability to destruct it or break it down. That is what mutations in ontogenes actually do.

Proteins play a decisive role in the vital activities of a living organism; correspondingly, this refers to the role of protein-coding genes as well. However, the latter successfully function in both homozygous and heterozygous states supporting panmixia and preventing emergence of nonuniformities in a genetic system. The emergence of a nonuniformity able to develop into separation of the initial genetic system into two subsystems incompatible with one another results from the specific feature of ontogenes, namely, their ability to act in homozygote and inability to act in heterozygote (lethality). It is no exaggeration to believe that it is the ontogenes with their ingenious features that determine the order of the living world in the form of isolated species.

The research into ontogenes opens a new layer in the genetic phenomena associated with variation. In this case, the variation bears no resemblance to the classical mutagenesis in the form of changes in DNA stably inherited in the course of generations. Referring to Muller, Hadorn defines genetic mutation defines as «a change in genetic material that transforms its certain relatively stable state into another relatively stable state; the new state is reproduced in hundreds of thousands of cell generations” 47 ^p.24. Unlike this (classical) pattern of mutagenesis, the mutations in ontogenes display a pattern of chain mutagenesis, in which an event of mutation in a gene does not end with the alteration of this gene but rather induces further instability of the overall genome, thereby producing secondary, tertiary, and so on mutations. In some parameters, this pattern resembles the so-called epigenetic variation but with an important amendment that it refers to a particular group of genes, that is, ontogenes. Some fragments of this variation in the form of the loss in lethal manifestation and homozygotization of dominant mutations are recorded and described, suggesting that variation in this case (1) develops in the course of the regular events taking place in genetic system; (2) follows a historically fine-tuned mechanism; and (3) most likely leads to two stable states of the genetic system, namely, a stable state preceding the period of variation (“old” norm) and a new stable state, that is, a new species.

Thus, the following four processes the existence of which was unknown or vague when studying Mendelian protein-coding genes take place with involvement of ontogenes:

(1) Editing of the program of individual development in germline cells of an individual. Its material basis is two parental genomes. The program is edited in the germline concurrently with the development of morphogenesis in the somatic primordium. The players in this process are ontogenes;

(2) Genetic instability induced by a mutation in an ontogene. The instability appears at all developmental stages of a living organism but is especially important in germline cells because it leads to inherited changes;

(3) Zygotic testing for compatibility of parental genomes. The genomes that entered with the egg and sperm are compared. The genomes in the pronuclei interact at a distance. If they match, they fuse to continue the ontogenesis; otherwise, they fail to fuse and the zygote dies. The inference on the interaction of genomes follows from the parental effect of chromosomal rearrangement in the maternal genome on the lethality of the mutation in ontogene received from father 293234; and

(4) Processing of ontogene manifestations. The species-specific program of individual development can be changed by a regular activity of ontogenes. Homozygotization of the mutation in ontogene with elimination of dominant lethal and recessive lethal manifestations demonstrate that these changes are feasible.

These processes are regular and lead to the preservation and reproduction of the species-level program of individual development. However, once a mutation emerges in an ontogene, these processes commence to work on the creation of a developmental program distinct from the ancestral one. Thus, they work on speciation. The proposed model of speciation describes the events that, in our view, should follow the emergence of a mutation in ontogene. The model may be named regeneration model. In general, this is the process of restoration of a species-level program of individual development disturbed by the mutation in ontogene.

The overall process starts from a mutation in an ontogene in a germline cell. The appearance of mutation interferes with the course of editing of the program of individual development. However, the mutation interferes with the process but not arrests it. The gamete is formed and takes part in fertilization. The disturbance is brought to light in the zygote carrying two parental pronuclei. They fail to interact in a routine manner and do not fuse. Thus, the zygote dies without even starting to develop. In part of cases, the appropriate interaction of the parental genomes still takes place thanks to the variants existing in a partner genome, as well as the syngamy, so that the viable progeny carrying the “mutation + suppressor of dominant lethality” is formed. In the language of genetics, we referred to this situation as the “mutation in ontogene residing in a permissive genotype”.

A favorable outcome combined (1) a partial isolation of mutant genome and (2) the permission for its further existence, including reproduction and secondary mutagenesis. Currently, it is not possible to specify the particular processes that take place in a persisting genome but we can assert that they do occur. This is suggested by both the changes in the energetics of mutants and the development of morphoses in progenies. Although morphoses are not inherited, their genetic nature is evident from the formation of groups of progenies with identical morphoses. Even the association of a defect with a particular side of the fly body is reproduced in the group of identical morphoses 272839. The facts described in Section 1.3 suggest a constantly ongoing alteration in the mutant genome.

The occurring changes can be regarded as the regeneration of the species-level program of individual development. The distinct trend of the removal of lethality in mutant stocks represents this particular regeneration. This commences from the elimination of dominant lethality followed by the removal of recessive lethality. The elimination of lethality indicates the ongoing regeneration. It forestalls an independent existence of a mutant clone on the background of the retained (and even deepening) isolation from the parental genotype. Individual facts of emerged sterile and later, fertile homozygotes demonstrate the progress in the regeneration of the program of individual development. In our earlier work 44, we describe the arguments favoring the assumption that the program of species-level ontogenesis is tested in the direction from the last to first stages of ontogenesis, while this program in the soma is implemented in the opposite direction.

The homozygotization of a mutation in ontogene can be regarded as the next stage in speciation. Homozygotization marks the transition from the nascent program of individual development to a fully autonomous existence, comprising a complete isolation from the nonmutant subpopulation and a standard (homozygous) existence of ontogene in the genome. The assumption on homozygotization of mutation as a stage in the construction of “novel ontogenesis” agrees with the data on the natural polymorphism of drosophila populations.

The researchers adhering to the chromosomal theory of speciation report numerous cases of the correlation between speciation and the formation of chromosomal rearrangements in the genome 4849505152. Note that they mean not the rearrangements in a heterozygous state, which are most abundant in natural populations and, as a rule, lethal in homozygotes, but rather the particular chromosomal rearrangements in a homozygous state. This means that the regulatory system of ontogenesis is remodeled in the interval between the emergence of a rearrangement in a heterozygous state to its inclusion into the genome of a new species.

The meaning of the transition of a natural chromosomal rearrangement from a heterozygous to a homozygous state in the proposed model of speciation consists in the transition of the corresponding mutation in ontogene residing in the rearrangement into a homozygous state. This statement explains a well-defined type of correlation between speciation and the formation of a rearrangement. They do correlate but the degree of correlation is rather low. The low correlation results from their indirect relation. Speciation tightly depends on the ontogenes within the rearrangement rather than the rearrangement itself.

Other facts also suggest an indirect role of the chromosomal rearrangement in the course of speciation. The drosophila males carrying inversions in a heterozygous state display a decreased fertility. This appears as a high death rate of their progeny at the stage of zygote (white egg) as in the case with the mutations in ontogenes. The death is independent of the presence of inversion in the progeny 53. Table 9 shows high death rates in the progeny of the drosophila males carrying inversions in their genome at the stage of white egg. The ratio of the classes “with inversion” to “without inversion” in the survived progeny is 1:1, thereby suggesting that the cause underlying the lethality of zygotes is not associated with the presence of a rearrangement there. The death is associated with the effect of the rearrangement on the function of the ontogenes in premeiosis 34. Apparently, the events occurring with chromosomal rearrangements in experiment and in nature are readily explainable if we associate the mechanism of speciation with the mutations in ontogenes.

The elimination of lethality in the mutants for ontogenes requires a comprehensive study. The very first data demonstrate that this process differs from that occurring with the Mendelian genes. Although Mendelian genes are chemically akin to ontogenes, the latter function in a fundamentally different manner. Remote interaction independent of the mutual arrangement of nucleotide sequences in space 30 directly leads to the inference that this interaction is provided not chemically but rather physically via the formation of a physical field of an electromagnetic type. The state of compaction putatively characteristic of the active ontogenes perfectly agrees with the electromagnetic nature of interaction 2931.

The assumed biophysical way of activity is not the only one for ontogenes. We postulate that the activity of ontogenes in germline cells consists in the production of small nuclear RNAs 54. Thus, ontogenes are most likely able to exert the activities of two types: biochemical activity with the help of small nuclear RNAs and biophysical activity with the help of wave action. The former is implemented in germline cells during editing of the program of individual development and the latter, while this program is deployed in the developing soma 32.

Zygotic selection is the process of self-development of genetic system, that is, the programmed response to an occurred damage in the system of individual development. The meaning of this response is the restoration of the coordinated work of genetic structures that guarantee the eventual construction of an actively functioning living organism. The restoration cannot be anything but the construction of an additional control structure supplementing the already existing ones. This is yet another increase in complexity performed according to the rules of the arrangement of the genetic system itself. Morphoses demonstrate which particular structure–function variants can be created. These are cellular ensembles 28. This can be referred to as the buildup of complexity. As is shown above, this is a special evolutionary mechanism. The following specific mechanisms are necessary for this mechanism to exist: (1) genome editing; (2) “explosive mutagenesis”; (3) zygotic selection; (4) isolation; and (5) processing of lethality.

Zygotic selection arranges a new model of individual development, Bauplan, and cellular ensemble for the future organism. However, this is not the entire program of individual development of an organism. To eventually develop into the organism, the cellular ensemble should be filled with proteins and energetically blend in with the ambient environment. The formed living system (an organism of a novel species) should be tested for its ability to exist under particular environmental conditions. Correspondingly, we assert that the selection of the fittest is obligatory and takes place concurrently with the zygotic selection. The material for the former is the mutations in Mendelian genes and the process itself is the famous Darwinian selection according to fitness. The zygotic selection and Darwinian selection act in cooperation.

However, note that the fact of zygotic selection changes the established view on the evolutionary process as the adaptation to habitat. The significance of Darwinian selection is not zeroed but rather considerably hypostatized. Correspondingly, the severe competitive relations between the adult organisms, which appear absolutely necessary in the case of the evolution that follows the Darwinian model, do not seem inevitable in this case. The genetic variants in the case of zygotic selection are rejected at the level of cells (zygotes) rather than adult organisms. That is why the general course of evolution looks more peaceful 2425 than it seemed earlier.