The authors have declared that no competing interests exist.
The existing hypotheses on speciation rely on Mendelian genes and mutations in them. However, genome-wide sequencing demonstrates that the Mendelian genes account less than one-tenth of the entire genome DNA. This means that a greater part of the genome has not yet been subject to large-scale evolutionary consideration. This paper deals with the conditional mutations in drosophila, which are mutations of the genes belonging to a special category (ontogenes) controlling the program of individual development. The ontogenes presumably reside in the DNA of intergenic spaces and introns. Conditional mutations display a number of properties absent in the mutations of Mendelian genes. These specific properties allow three key problems in speciation to be solved: (1) the possibility of emergence of new traits as a result of sequential mutagenesis; (2) selection of mutants; and (3) establishment of isolation. We have shown that (1) the mutations in ontogenes are able to form new multigenic regulatory blocks that escape selection during their creation; (2) mutations in ontogenes allow for existence of constantly acting zygotic selection, which is by no means less important for speciation than Darwinian selection; and (3) owing to their conditionally lethal effect, the mutations in ontogenes are able to create biological isolation barrier. This gives the grounds for assuming that the emergence of mutations in ontogenes is a necessary condition for speciation.
The classical period in development of genetics gave birth to the genetic foundations of ontogenesis and phylogenesis, bringing the corresponding areas of knowledge to a higher level. However, genetics have encountered difficult questions. The first question is how it is possible to explain the obligate similarity of individuals within a species with the help of changeable (those that form viable mutant variants) genes
The attempts to answer these and other questions have suggested existence of different genes, other than the Mendelian ones
We have assumed that the genes responsible for the species-level program of individual development are obligately homozygous; hence, the mutations that lead to speciation should look a sort of paradoxically. They should be lethal in a heterozygous state and not lethal as homozygotes
The very fact that conditional mutations were found in drosophila
The goal of this work was to explicate reasoned conclusions (decisions) on three pivotal problems in phylogenesis. The first problem is the possibility of a multistep speciation. The assumption of stepwise speciation looks justified, even the only possible, but its implementation with the help of Mendelian genes alone faces serious obstacles. The second problem is the role of selection in speciation, formulated by Darwin and still debated. The third problem is the mechanism underlying the isolation during speciation, which is among the most important in this field.
All these problems have a deep history, long lists of the papers that have attempted to resolve them, and the generally accepted fact that the solutions are yet absent. The postulates formulated here are based on analysis of the unusual properties of ontogenes earlier discovered in experiments. This paper is a kind of a
The research into ontogenes has passed through several stages. The first stage consisted in theoretical prediction of the earlier unknown genes and formulation of the search rules allowing the mutations in these genes to be found
The second stage consisted in the description of how these mutations manifested themselves in permissive genotypes. This manifestation pattern drastically differed from the pattern characteristic of Mendelian mutations
The method for obtaining conditional mutations itself suggests that these mutations are damages in DNA (DNA genes)
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Template | DNA region | DNA region |
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Mechanism of implementation | DNA–mRNA–protein | DNA–nRNA–DNA conformation |
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Site of gene activity | Soma | Germline and soma |
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Time of activity | The entire period of soma development | Gametogenesis to meiosis and soma |
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Final product | Polypeptide | nRNA |
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Allelic state | Two products | One product (duplex) |
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Status in genome | Unique | Multiplied |
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Pattern of interaction in genome | Independent | Dependent |
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Typical gene function | Structural | Regulatory |
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Dependence of gene function on position in the nuclear space | Independent | Dependent |
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The combination of the effect of a chromosomal rearrangement and the phenomenon of parental inheritance
Thus, the living organism is under a double control of the Mendelian genes and ontogenes, the latter being the most stringent. The effect of ontogenes is of a systemic character, since it depends on the ontogenes of both the own genome and the genome of the partner in cross. The ontogene is manifested in a dominant manner excluding any changes. Any change in the ontogene in one dose, as a rule, leads to death at the earliest embryonic stage. A mutation in an ontogene can be saved from death only if this ontogene loses its activity. The control by ontogenes relies on two entities—nucleotide code of DNA and conformation of DNA molecule.
The control by Mendelian genes is milder. The genes act autonomously (independent inheritance and manifestation) and, as a rule, in a recessive manner (at a double dose). The trans-alleles of Mendelian genes act independently and their mutations are typically not lethal. The Mendelian genes control only material aspect of the living matter, i.e., protein.
The idea of genome inhomogeneity with respect to its composition has been repeatedly posed in genetics. The two components of the genome in terms of cytogenetics are euchromatin and heterochromatin
Starting from the works by Korzhinsky
Trying to bypass this difficulty, it was proposed that a putative gene duplication took place before the corresponding mutation
The mentioned assumptions were made with respect to traditional Mendelian mutations and Mendelian genes. Genetics has not known any other genes and mutations. We believe that this is why the idea of sequential mutagenesis is inconsistent. On the contrary, conditional mutations of ontogenes, which are considered here, may represent the particular material for origination, spreading, and retention of a set of mutationally altered genes that represent a new species. The idea of speciation via sequential mutagenesis is quite realistic if it is considered with respect to ontogenes.
Mutant male stock no. | Cross: 2♀ y × ♂+ | Cross: 6♀ y × ♂+ | Fecundity of male |
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Total number of progenies | Share of daughters in progeny | Total number of progenies | Share of daughters in progeny | ||
1 | 119 | 0.00 | 191 | 0.00 | 0.02 |
2 | 650 | 0.00 | 435 | 0.00 | 0.15 |
3 | 112 | 0.00 | 180 | 0.00 | 0.12 |
4 | 114 | 0.00 | 293 | 0.00 | 0.07 |
5 | 50 | 0.00 | 303 | 0.02 | 0.14 |
6 | 47 | 0.00 | 283 | 0.02 | 0.14 |
7 | 47 | 0.02 | 100 | 0.00 | – |
9 | 182 | 0.07 | 529 | 0.00 | 0.40 |
10 | 162 | 0.03 | 297 | 0.04 | 0.09 |
27 | 68 | 0.00 | 93 | 0.00 | 0.18 |
29 | 15 | 0.07 | 61 | 0.00 | 0.14 |
30 | 122 | 0.00 | 115 | 0.00 | 0.19 |
31 | 106 | 0.00 | 83 | 0.00 | 0.15 |
32 | 81 | 0.00 | 117 | 0.00 | 0.13 |
33 | 144 | 0.00 | 90 | 0.00 | 0.16 |
34 | 88 | 0.00 | 110 | 0.00 | 0.12 |
26 | 92 | 0.03 | 89 | 0.01 | – |
35 | 102 | 0.03 | 115 | 0.04 | 0.35 |
36 | 95 | 0.00 | 110 | 0.01 | 0.14 |
37 | 52 | 0.02 | 68 | 0.04 | 0.14 |
38 | 54 | 0.06 | 84 | 0.01 | 0.10 |
The ratio of adult progenies to the number of laid eggs.
The mutations in males led not only to the lethality of daughters, but also to partial lethality of the sons. This is suggested by the ratio of the eggs laid by
The question arises on how we can explain the absence of lethal effect of mutation in male (father) once it is present in its daughters. There is the only answer: the mutant gene is inactive in male.
It is evident from the example with conditional mutations in the drosophila X chromosome that the mutations in ontogenes are able to escape elimination by selection. The mutant variants of ontogenes can be preserved in special genomes over infinitely large number of generations. If so, a network of mutant regulators forming the basis for a new trait can be constructed involving the mutations in ontogenes generated as a result of sequential mutagenesis
Emergence of a new trait will look as a “sudden” although this is a result of a long-term changes in the genome. If a particular combination of mutations is beneficial, nothing prevents it from becoming homozygous since it is contained in the genomes of sibs in a heterozygous state. Something similar takes place in the long-term stocks of the mutants in the X chromosome (
The recovered mutations in the X chromosome were maintained in the stocks heterozygous for the In (1) Muller-5 inversion
The loss in lethal manifestation of some mutations was accidentally discovered in 2001 in the experiments on determining the level of dominant lethality. Males from stocks nos. 1, 3, 5, 27, and 33 (attached -X stocks) commenced to give female progenies (daughters) when crossed to
Three additional mutations (nos. 29, 38, and 41) lost their lethality in 2002 and another one (no. 35), in 2004. Some stocks displayed a decrease in lethality rather than its complete loss. Daughters started to appear in progeny although their rate did not reach the normal level of 50% (nos. 7 and 9–11). In total, nine mutations of the 22 mutant stocks completely lost their lethality over 2000–2004 and five mutations become semilethal. This phenomenon was named “loss of lethality” (see
Note that the mutant X chromosome does not lose its recessive lethal manifestation in the stock despite the cases when the conditional lethality is lost in the test with
Stock no. | 2000 | 2001 | 2002 | 2004 | |||||
Total number of progenies | Share of daughters | Total number of progenies | Share of daughters | Share of daughters | Total number of progenies | Share of daughters | Total number of progenies | ||
1 | 191 | 0.00 | 13 | 199 | 77 | ||||
2 | 435 | 0.00 | 4 | 0.00 | 259 | 0.02 | 36 | 0.03 | |
3 | 180 | 0.00 | 20 | 311 | 95 | ||||
5 | 303 | 0.02 | 33 | 265 | 83 | ||||
6 | 283 | 0.02 | 2 | 0.00 | 111 | 0.02 | 39 | 0.05 | |
7 | 100 | 0.00 | 3 | 0.00 | 44 | 63 | |||
8 | 216 | 0.07 | 5 | 0.00 | 90 | 0.09 | 49 | ||
9 | 529 | 0.00 | 7 | 0.00 | 169 | 81 | 0.04 | ||
10 | 297 | 0.04 | 7 | 0.00 | 69 | 57 | |||
11 | 409 | 0.06 | 4 | 0.00 | 82 | 55 | |||
26 | 89 | 0.01 | – | 0.00 | 175 | 0.07 | 40 | 0.02 | |
27 | 161 | 0.00 | 29 | 113 | 92 | ||||
29 | 76 | 0.00 | 4 | 0.00 | 171 | 80 | |||
30 | 115 | 0.00 | 8 | 0.00 | 109 | 0.02 | 71 | 0.00 | |
31 | 189 | 0.00 | 8 | 0.00 | 138 | 0.01 | 70 | 0.03 | |
32 | 198 | 0.00 | 4 | 0.00 | 74 | 0.00 | 53 | 0.02 | |
33 | 234 | 0.00 | 23 | 214 | 88 | ||||
34 | 198 | 0.00 | – | 0.00 | 62 | 0.00 | 54 | 0.02 | |
35 | 115 | 0.04 | 12 | 0.00 | 162 | 83 | |||
36 | 110 | 0.01 | 5 | 0.00 | 106 | 0.02 | 54 | 0.07 | |
38 | 84 | 0.01 | 3 | 0.00 | 80 | 51 | |||
41 | 100 | 0.01 | 5 | 0.00 | 331 | 106 |
Loss of a lethal effect of mutation.
** Reduction in a lethal effect of mutation.
The current theory of evolution relies on Darwinian selection. This selection implies elimination of the individuals poorly fit to environmental conditions and a decrease in fecundity, which reduces its genetic contribution to the next generation. Darwinian selection acts among the adult progenies, i.e., among the organisms in the postnatal period. The concept of environment is relevant to these particular individuals.
Note that the age of the organism that is subject to selection is very important. This information allows us to understand which particular genes are potentially involved in selection under the influence of environment. Naturally, these are the genes becoming active from the moment the zygote is formed. Until recently, all genes of an organism have been regarded as such genes. Thus,
The discovery of ontogenes made it clear that the Mendelian genes are by no means the only genes of the organism. There is another kind of genes, ontogenes. They are no less but rather more abundant than the Mendelian genes. Ontogenes commence their activity earlier, during the maturation of gametes in parental organisms
Male mutant strain | Total number of laid eggs | Lethality (%) at the stage of | Live imagoes (%) | |||
White egg | Brown egg | Larva | Pupa | |||
1 | 50 | 92 | 2 | – | – | 6 |
2 | 50 | 81 | 13 | 2 | – | 4 |
3 | 50 | 76 | 18 | - | – | 6 |
5 | 100 | 65 | 28 | 3 | – | 4 |
6 | 50 | 80 | 8 | – | – | 12 |
7 | 50 | 52 | 32 | 6 | 2 | 8 |
8 | 50 | 90 | 6 | – | – | 4 |
10 | 50 | 68 | 20 | 6 | – | 6 |
11 | 50 | 56 | 30 | 2 | - | 12 |
27 | 50 | 72 | 8 | 6 | – | 12 |
29 | 50 | 92 | 6 | – | – | 2 |
30 | 50 | 96 | 2 | 1 | – | – |
31 | 50 | 90 | 4 | 2 | - | 4 |
32 | 50 | 46 | 32 | 8 | – | 14 |
33 | 50 | 50 | 28 | 6 | 2 | 14 |
36 | 24 | 33 | 54 | – | 6 | 7 |
38 | 40 | 68 | 22 | 5 | – | 5 |
41 | 50 | 90 | 6 | – | – | 4 |
Average | 51 | 72 | 18 | 3 | 0.6 | 7 |
Male stock no. |
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Total number of progenies | Rate of females | Total number of progenies | Rate of females | Total number of progenies | Rate of females | Total number of progenies | Rate of females | Total number of progenies | Rate of females | |
1 | 191 | 0.00 | 169 | 0.06 | 87 | 0.01 | 138 | 0.01 | 148 | 0.03 |
2 | 435 | 0.00 | 236 | 0.12 | 76 | 0.11 | 38 | 0.05 | 173 | 0.13 |
3 | 180 | 0.00 | 469 | 0.63 | 190 | 0.43 | 128 | 0.59 | 331 | 0.58 |
4 | 293 | 0.00 | 209 | 0.08 | 162 | 0.04 | 86 | 0.00 | 213 | 0.08 |
5 | 303 | 0.02 | 107 | 0.27 | 112 | 0.01 | 46 | 0.04 | 96 | 0.22 |
6 | 283 | 0.02 | 136 | 0.23 | 106 | 0.23 | 64 | 0.00 | 112 | 0.25 |
7 | 100 | 0.00 | 154 | 0.36 | 135 | 0.21 | 13 | 0.23 | 145 | 0.39 |
26 | 89 | 0.01 | 121 | 0.24 | 210 | 0.30 | 46 | 0.02 | 69 | 0.28 |
27 | 93 | 0.00 | 123 | 0.05 | 117 | 0.02 | 79 | 0.00 | 79 | 0.06 |
29 | 61 | 0.00 | 203 | 0.49 | 122 | 0.57 | 18 | 0.00 | 128 | 0.55 |
30 | 115 | 0.00 | 142 | 0.38 | 100 | 0.17 | 93 | 0.09 | 106 | 0.19 |
31 | 83 | 0.00 | 118 | 0.19 | 123 | 0.22 | 121 | 0.04 | 195 | 0.27 |
32 | 117 | 0.00 | 183 | 0.13 | 101 | 0.19 | 80 | 0.14 | 117 | 0.35 |
33 | 90 | 0.00 | 144 | 0.34 | 123 | 0.24 | 42 | 0.17 | 100 | 0.22 |
34 | 110 | 0.00 | 115 | 0.25 | 71 | 0.07 | 31 | 0.29 | 41 | 0.15 |
36 | 110 | 0.01 | 108 | 0.25 | 127 | 0.20 | 105 | 0.01 | 323 | 0.46 |
A maternal variant of zygotic lethality appears in the experiments with autosomal rearrangements (
Male mutant stock no. | Female |
Female |
Female |
Female |
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Daughter + | Son
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Daughter + | Son |
Daughter + | Son |
Daughter + | Son |
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1 | – | 230 | – | – | 178 | 163 | – | – | 107 | 57 | – | – | 115 | 8 |
2 | – | 230 | 14 | 13 | 127 | 134 | 4 | 3 | 70 | 72 | – | – | 42 | 7 |
4 | – | 270 | 9 | 4 | 185 | 159 | 1 | 7 | 86 | 81 | – | – | 162 | 7 |
5 | – | 197 | 23 | 21 | 80 | 95 | 6 | 4 | 47 | 48 | – | – | 37 | 3 |
27 | 2 | 167 | 1 | 0 | 102 | 113 | 2 | 1 | 53 | 65 | – | – | 9 | 2 |
29 | 4 | 163 | 32 | 27 | 71 | 56 | 26 | 24 | 55 | 20 | 6 | 6 | 88 | 10 |
30 | – | 184 | 15 | 13 | 81 | 76 | 9 | 12 | 60 | 47 | – | – | 38 | 6 |
31 | – | 242 | 32 | 20 | 127 | 102 | 5 | 4 | 28 | 29 | – | – | 70 | 6 |
32 | – | 197 | 22 | 10 | 90 | 77 | 9 | 17 | 36 | 32 | – | – | 48 | 2 |
33 | – | 209 | 20 | 18 | 95 | 101 | 11 | 8 | 87 | 47 | 24 | 2 | 85 | 12 |
34 | – | 140 | 11 | 14 | 88 | 101 | 25 | 20 | 68 | 54 | – | 10 | 103 | 3 |
The above listed specific features of zygotic lethality and, in particular, the parental effect, suggest that zygotic lethality is prepared by the processes that involve the genetic material during maturation of reproductive products in the germline tissue. The processes go on on a regular basis during formation of each gamete
The existence of zygotic selection fundamentally alters the concept of evolutionary development. In addition to Darwinian selection, which involves the adult organisms, the germ cells are selected on a regular basis. This selection takes place at the stage of synkaryon and zygote formation. The internal factors of the organism are important for this selection rather than external environment. There is no more talk about the adaptation to external environment in the case of zygotic selection.
A regular adjustment of the program of individual development, occurring when each gamete is formed, precedes the zygotic selection
The fact that zygotic selection exists leads to
This issue was already considered when discussing Darwinism and orthogenesis
The individuals belonging to different species either do not cross with each other or give infertile progeny. Owing to this property, referred to as isolation, all living matter exists as hereditary separate sets, individual species. From the standpoint of the modern evolutionary synthesis, the genome of a new species is constructed of the mutations in the Mendelian genes of the precursor species. This approach to speciation does not allow the phenomenon of isolation to be explained. Indeed, mutations of Mendelian genes are unable to provide isolation of a newly formed species. The mutants in Mendelian genes are full-fledged members of the species-level community without any trend of isolation. That is why there are no grounds for isolation of a new species in this case.
On the contrary, mutations in ontogenes are a perfect material for establishment of isolation. Each mutation in ontogene is a lethal with a particular range of action. A mutation in ontogene (= conditional mutation) causes death of the progeny that received the corresponding lethal as well as the progeny that did not get this lethal (parental effect) (
The mutations in ontogenes possess a unique pattern of lethal manifestation. They are lethal even in heterozygous state, except for permissive genotypes. We believe that it is the ability of an ontogene to be inactive that allows the mutant ontogenes to escape elimination from population
Once becoming mutant, an ontogene commences acting as both speciation and isolation factors. The event of new species formation is the event of homozygotization of the mutant ontogenes. It marks creation of a new congruous regulatory system, which is not lethal but rather beneficial from biological standpoint. The fundamental significance of ontogenes in solving the problem of isolation was recognized immediately on appearance of the first data on conditional mutations
A lethal effect of mutations in an ontogene displays remarkable features, described above in the section on zygotic selection. The lethal effect depends on both the mutation itself and the gamete of the partner in mating. Mutation can lose its lethal manifestation in the crosses with a certain partner. This has been shown experimentally (
This picture resembles the situation with chromosomal rearrangements. As a rule, the chromosomal rearrangements from natural drosophila populations are lethal in a homozygous state
The speciation issues considered above were formulated as early as the classical period in development of genetics. The concept of ontogene can enhance their resolution. The last section of this paper discusses the new questions in evolutionary transformation of the living matter. These questions arise with the emergence of the concept of ontogene on the genetic horizon.
The emergence of a new genetic unit, an ontogene, transforms the genome from a one-component to two-component entity. The question arises on the similarity and distinction between these components. In molecular terms, these elementary units of the genome are similar, being represented by DNA sequences; however, they code for different processes, namely, regulatory (switching genes on and off) and synthetic (protein synthesis). Changes in the functions of DNA region in the course of evolution cannot be excluded. Both functions—regulatory and synthetic—had sometimes originated from the same structural material (a polynucleotide).
The data reported here directly suggest the presence of zygotic selection and demonstrate that the object of selection is variants of regulation implemented by ontogenes. Presumably, this mechanism is used in order to incorporate new regulatory scenarios underlying the new species. This mechanism may represent the long-awaited
The process of creation of a new species when referring to the constantly going zygotic selection must also continue after the isolation is formed. The organism of a new species now can get rid of some functions and structures of the progenitor species that became needless and energetically unbeneficial. This process can be implemented via both Darwinian and zygotic selections.
Experimental data show emergence of gene, chromosome, and genome instabilities in the mutants carrying conditional mutations
The heading for this section lists the biological aspects in considering a living material object. A genetic view on the evolutionary process as compared with a biological view is evidently narrower. Mendelian genes allow for consideration of only substantial aspect. Indeed, it is possible to explain formation of proteins, the major part of a living organism, using the concept of Mendelian gene. However, Mendelian genes contain no information about when (temporal aspect) and where (spatial aspect) these genes should act.
It is ontogenes that open the road for studies into a spatiotemporal aspect in living objects (ontogenesis and phylogenesis). Ontogenes are involved in construction of the program for individual development of a species
Until recently, genetics has not touched the energy aspect of a living organism. However, this aspect quite unexpectedly appeared when studying the ontogenes. The mutants in ontogenes display a higher level of the basal metabolism as well as high locomotor activity
Molecular analysis of genomic DNA in eukaryotes shows that most of it is not involved in protein synthesis
In this paper, we have analyzed the specific features of the mutations in ontogenes, including (1) their conditional manifestation; (2) lethal effect; and (3) parental effect. These features distinguish ontogenes from the traditional Mendelian genes. Our data demonstrate that the specific features of ontogenes make it possible to resolve some problems in phylogenesis that have emerged because of the classical idea of a single-component genome comprising only Mendelian genes.
It is worth noting that we consider here three evolutionary problems at once although each of them deserves a separate consideration. The chance to simultaneously advance in all three directions demonstrates that the central idea postulating existence of the genome composed of Mendelian genes and ontogenes is an adequate one. This idea forms the background for a new approach to the research into the genetic system.
The authors are grateful to the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences for support of this work under project no. 0324-2019-0042.