Shabanov (2002) What will be the third synthesis in evolutionary theory?

Author’s pre‑notice to the online publication Thanks to the kindness of the creator of “Macro‑evolution,” Alexander Markov, I obtained the opportunity to publish an article written in 2002; now I am posting it on “Batrachos.” I must admit that this article received a critical response and was sent back for revision by the editorial board of the “Journal of General Biology,” to which I submitted it. I am very grateful for the criticism expressed by Alexei Merkurievich Gilyarov. Summarizing its focus briefly, I can say that it concerns insufficient “expansion” and the justification of several statements. Unfortunately, my attempt to revise this article convinced me that, to sufficiently substantiate the idea presented, the article would need to be turned into a book. At the same time I hope that, even in its current form, this text will serve as material for discussion with like‑minded colleagues and constructively oriented “opponents” – supporters of alternative views. Among the reviews of the manuscript, the response of Mikhail Alexandrovich Shishkin was especially important to me. This response also turned out to be sharply critical. From Mikhail Alexandrovich’s point of view, the explanatory approaches of the synthetic and epigenetic theories are fundamentally different, and their mixture, demonstrated in the proposed article, cannot lead to anything good. In my view, such a combination is necessary. I think that one of the pressing tasks in building a new evolutionary theory is to develop a sound classification of traits according to the nature of the control of their development. When dealing with biochemical traits of bacteria (especially traits such as “enzyme is broken”/“enzyme is not broken”), the methodology of the synthetic theory of evolution proves entirely sufficient. If we are interested in the emergence of new adaptations in representatives of rapidly evolving, highly organized groups of organisms, we will not be able to explain them in the language of allele selection and will have to turn to the epigenetic theory approach. Another necessary pre‑notice concerns the use of the term “epigenetic.” This concept can be employed in several different senses, even without invoking the famous debate between epigeneticists and pre‑formists in the history of developmental biology. These senses can be called molecular and ontogenetic. Both, in general terms, correspond to the definition by K. H. Waddington, the author of this concept in its modern interpretation. According to Waddington, epigenetics is the branch of biology dealing with causal interactions between genes and their products that form the phenotype. The gap between the molecular and ontogenetic approaches to epigenetics reflects the gap between research levels available to modern science. We can study development either at the level of individual molecules or at the level of ontogeny as a whole. Describing the mutual influence of all factors governing development even at the level of a single cell is an intractable task for contemporary science. However, Waddington himself used the term mainly in the ontogenetic sense, as, for example, in his well‑known metaphor of the epigenetic landscape. The ontogenetic sense of this concept is used in this article (as in the works of M. A. Shishkin). I consider the purpose of this online publication to be a discussion of the ideas presented herein. I would be grateful for constructive criticism. D. A. Shabanov What will be the third synthesis in evolutionary theory? In the first half of the 20th century, the crisis of classical Darwinism (the first evolutionary synthesis) gave rise to the second synthesis – the synthetic theory of evolution (STE). The current crisis of STE should lead to a third synthesis that will overcome its reductionist limitation. Possible elements of the third synthesis are being developed today relatively independently of each other. These include V. A. Krasilov’s ecological theory, non‑saltationism, concepts of species monomorphism, punctuated equilibrium, “evolution of evolution,” etc. One of the consequences of M. A. Shishkin’s epigenetic theory, which may become the core of the third synthesis, is a new approach to solving the problem of the emergence of biological purposiveness. It can be hypothesized that within the third synthesis an explanation will be found for the mechanism by which whole complexes of traits, the multilevel nature of evolution, and changes in its tempo are acquired during evolution. On the eve of the third evolutionary synthesis According to the periodization of the development of evolutionary thought proposed by N. N. Vorontsov (1999), Darwinism became the first broad synthesis of evolutionary ideas. At the end of the 19th–beginning of the 20th century, the crisis of the first synthesis occurred. Some of the problems that caused this crisis were solved by the second synthesis – the synthetic theory of evolution (STE). The present time is a period of crisis of STE preceding the third evolutionary synthesis. Some features of the forthcoming synthesis began to coalesce several decades ago (e.g., Schwartz, 1967; Krasilov, 1984; Shishkin, 1987; Nazarov, 1991), yet this process is far from complete. The current state of evolutionary theory allows us to anticipate several characteristics of the third synthesis. The crisis of evolutionism stimulated the emergence of a number of new theories. The main idea of this work is the assertion that the concepts mentioned in the article, which examine the evolutionary process from different perspectives, are well compatible with each other. Their integration, in the author’s opinion, should lead to the emergence of a third evolutionary synthesis. After characterizing some features of the STE crisis, this article examines the epigenetic theory of evolution, which, in the author’s view, should become the core of the new synthesis. Some authoritative evolutionists have expressed the opinion that the accumulation of new data does not replace STE with a new synthesis, but merely modifies and expands STE itself. As an analogy one may mention the views of I. I. Schmalhausen, who considered the distinction between Darwinism and neo‑Darwinism (STE) unnecessary. According to the author, in this matter science as a whole (in this case – evolutionary biology) should not be conflated with any particular theory (Darwinism or STE). Science develops by moving from one set of views to another. A theory is a product of a particular time, characterized by relatively coherent perspectives. Thus, for STE the representation of evolution as a change in allele frequencies in populations is characteristic. Abandoning this approach does not broaden the scope of STE, but requires a transition to another theory. Crisis of STE Both the initial success and the current crisis of STE are linked to its reductionism. Its manifestations are diverse: reduction of speciation and macroevolution to microevolution, detachment of population evolution from changes in biogeocenoses and the biosphere, and the acceptance of the assumption of independent evolution of individual genes. In particular, the mathematical theory of selection is based on the assumption that all alleles have a constant fitness value. This ignores important factors such as the influence of genotype, the uncertainty of ontogenetic outcomes (conditioned by interactions of external and internal factors), and environmental heterogeneity. When naming the problems solved thanks to the synthesis of evolutionary and genetic theory, STE proponents often cite F. Jenkin’s (Jenkin, 1867) criticism of Darwinism. According to this author, an adaptive trait cannot persist across generations because of “dilution” when its carriers mate with individuals lacking the trait. “After the rediscovery of Mendel’s laws and the proof that the factors determining the development of inherited traits are transmitted to offspring without fragmenting, ‘Jenkin’s nightmare’ was dispelled” (Soifer, 1975, p. 309). However, it is clear that Jenkin did not refer to monogenic traits: “Suppose a white man is shipwrecked on an island inhabited by blacks… Our shipwrecked hero will probably become king; he will kill a great many blacks in the struggle for existence; he will have a huge number of wives and children, while many of his subjects will live and die as bachelors. … In the first generation there will be several dozen clever young mulattoes, on average intellectually superior to the blacks. We might expect that for several generations the throne will be occupied by a more or less yellow king; but could anyone believe that the whole island would gradually acquire a white or even yellow population, or that the islanders would acquire energy, bravery, inventiveness, perseverance, self‑control, endurance, by virtue of which our hero killed so many of their ancestors and sired so many children—that is, the qualities actually selected by the struggle for existence, if it can select anything?” (Jenkin, 1867, pp. 289–290). For evaluating Jenkin’s reasoning it is irrelevant that racial superiority does not exist and that the named traits are mainly inherited culturally. If an individual’s adaptiveness depends on a complex of independently inherited traits, the “scattering” of such a complex should impede selection. The assumption that each of these traits would be selected independently of the others has been refuted within STE itself. Developing the mathematical theory of selection, J. Haldane (Haldane, 1957) showed that selection on several independent allele pairs is ineffective due to the increasing genetic load and reduced reproductive potential of the population. The assumption of prolonged selection on many separate genes, each contributing at the phenotypic level (especially characteristic of sociobiology that developed on the basis of STE), not only contradicts Haldane’s calculations but is also contradicted by data on the relatively small number of genes in humans and other species obtained from genome‑sequencing projects. The discovery of genetic diversity among carriers of normal phenotypes from natural populations by S. S. Chetverikov contributed to the creation of STE. However, from the STE perspective this phenomenon has never received adequate explanation (Leventin, 1978). It is equally difficult to establish the causes of temporally stable differences between neighboring populations and breeding groups observed in many species. To explain these phenomena, STE supporters invoke gene drift. In fact, this means a rejection of the selectionism underlying STE itself. Studies of the phylogeny of many taxa have shown the fallacy of the STE‑typical view of evolution as predominantly divergent, closely linked to the recognition of mutation nondirectionality and gene drift. Parallelisms and convergences are the norm in the emergence of most groups (Tatarinov, 1987). From the foregoing it follows that the theory that will replace STE must explain the mechanism by which coordinated complexes of adaptive traits are acquired during evolution. Some other features of the second synthesis crisis are examined further in comparison with alternative views. Epigenetic theory of M. A. Shishkin A central role in the third evolutionary synthesis (Hrodnytsky, 2001) may be played by M. A. Shishkin’s concept (1987, 1988), which he called the “Schmalhausen‑Waddington epigenetic theory of evolution.” Although the author draws on the ideas of I. I. Schmalhausen and K. H. Waddington, he arrives at substantially different conclusions. Therefore, it is probably more accurate to speak of the “epigenetic theory of M. A. Shishkin.” The key notion of this theory is the epigenetic system (hereafter ES), the set of interactions among genetic and other factors influencing ontogeny. According to this theory, individual hereditary endowments are not the direct cause of particular phenotypic features, but only affect the system that controls ontogeny. As a result, natural selection selects and reproduces in offspring not individual alleles or traits, but whole phenotypes. Regardless of which factors (genetic and non‑genetic hereditary endowments, external influences) trigger the development of an adaptive trait, its bearers will contribute relatively more to the formation of the next generation. Descendants inherit from their parents not only genes but also the overall organization of the ES. If the nature of selection remains the same, those that reproduce the previously selected adaptive phenotypes gain an advantage. Selection of such phenotypes should lead to a restructuring of the ES that enhances the stability of the developmental trajectories (creodes) it generates. While the population norm remains adaptive, selection reshapes the ES so that, with maximal genotypic diversity, normal ontogenetic progress is ensured. The consequence of this is precisely the genetic diversity of normal‑phenotype carriers discovered by S. S. Chetverikov in natural populations. Selection against the established phenotypic norm destabilizes the epigenetic creodes leading to it. As a result, a series of relatively discrete aberrations appears, corresponding to possible alternative creodes for a given ES. Selection in favor of one of them increases the stability of its realization in ontogeny. Thus, according to the considered views, new traits arise through the transformation of a species‑specific ES by selection. In this process, developmental variants that initially appear as aberrations become stabilized. The above is supported by numerous facts. As is well known, there is no one‑to‑one gene‑trait correspondence. The action of each gene depends on other hereditary endowments and is characterized by a certain expressivity and penetrance. The expression of mutant alleles is especially unstable when their ontogenetic realization is not stabilized by selection: even dominant mutations do not always fail to manifest in the homozygote. R. Goldschmidt (Goldschmidt, 1940) showed that the same trait may develop or not develop due to very different causes (different influences on the ES): both mutations of different genes and environmental impacts. The development of the epigenetic theory began with Waddington’s experiments, which demonstrated the stabilization of labile traits. In these experiments, selection for the ability to produce morphs (developmental anomalies) such as dumpy or bithorax in response to temperature or toxic stress led to these morphs developing even under normal conditions (Waddington, 1957). From the perspective of M. A. Shishkin’s concept, such a result is due to a restructuring of the ES that stabilizes the selected developmental pathways (rather than the emergence of dumpy or bithorax genes). In G. H. Shaposhnikov’s experiments (1978), selection of aphid morphs induced by a change of host plant gave rise to new, morphologically and ecologically distinct forms of experimental animals that were reproductively isolated from the originals. Epigenetic system as a level of integration A regular question arises: should the ES be regarded as a separate level of developmental regulation, if gene interactions are already considered in classical genetics? Is the concept of “epigenetic system” not simply synonymous with “genotype”? Obviously, delineating a separate structural or functional level of integration is justified when new (emergent) properties appear at that level, absent at lower levels. Underestimating one of the essential integration levels (level n) leads to a typical reductionist error: features of level n + 1 will be interpreted as the result of level n – 1 functioning. Consequently, the emergent properties of level n become inaccessible to study. Ontogeny, one of the most complex known processes, is regulated by diverse hereditary endowments, environmental influences, and their interactions. The equifinality of individual development and the externally conditioned possibility of its adaptive modification are set at the level of the ES as a whole, not at the level of individual genes. Considering this level is a prerequisite for studying the most important properties of living systems. Where are the mechanisms that channel development localized? This question is no more precise than, for example, asking where in the brain a particular thought resides, or where in the biosphere the regulator of atmospheric oxygen content is located. When dealing with complex systems (ES, brain, biosphere, etc.), pinpointing the localization of their emergent properties is simply impossible, because they are defined by the network of connections among all elements. Nevertheless, epigenetic mechanisms also manifest at the level of individual hereditary endowments, cognition is linked to brain cell function, and biospheric homeostasis is achieved through the activity of individual organisms. It is natural that the core of the first evolutionary synthesis was the study of phenotypic variability and its interaction with the environment—the most “obvious” level of regulation of historical development (Fig. 1). Studying the relatively simple mechanism of hereditary variability and the influence of selection on the frequencies of hereditary endowments led to the second synthesis. It appears that during the third synthesis the significance of the most complex level of developmental regulation—the ES—will be understood. [IMG_1] Fig. 1. Role of the ES in governing individual and historical developmentOvercoming “gene‑centrism” Interpreting the experiments described above on the fixation of morphs as a result of selection, K. H. Woodington called the phenomenon he discovered genetic (rather than epigenetic) assimilation. To explain the results of similar experiments, it was hypothesized that initial pheno‑adaptations are replaced by geno‑adaptations (Schmälgausen, 1938; Gauze, 1984). This is based on the belief that each trait is determined by specific genes. Such “gene‑centrism” remains widespread to this day. For example, the statement that “mutations and their combinations serve as material for evolution,” N. N. Vorontsov (1999, p. 470) regards as one of the positions “about which evolutionists do not argue.” It has been shown that closely related species can differ substantially in the organization of their genetic material, for instance in the proportion of different types of sequences (Korochkin, 1985). At the same time, the closeness of these species is linked to the similarity of their ES. Apparently, the similarity of the ES of different species is the reason for the existence of homologous series of variability described by N. I. Vavilov. Since homologous developmental aberrations may have different genetic bases, the homologous entities are not genes but epigenetically determined creodes. As A. S. Rautian (1993) points out, by virtue of A. A. Lyapunov’s principle of the relativity of information content, information in the genotype is accessible only to a certain competent user. This user is not the phenotype as a whole, but specifically the ES, initially inherited from the previous generation (e.g., during oogenesis) and then changing during ontogeny. Changes in phenotypes during evolution are linked not so much to changes in genes (and other hereditary determinants) as to changes in the ES. The same nucleotide sequence read by the ES of different organisms can have completely different meanings for them! The possibility, popularized in a film (and novel), of obtaining a dinosaur by transplanting its genes into a frog egg is an unfounded fantasy: such a procedure could at most produce a frog embryo with disrupted genotype‑ES interaction. As is known, during anthropogenesis human DNA sequences have undergone only minor changes. Thus, the difference between humans and chimpanzees lies less in having different genes than in possessing a reorganized ES. “Gene‑centrism” is also contradicted by the growing number of examples of non‑genetic inheritance. Apparently, dynamic inheritance (the transmission of a specific protein‑molecule conformation), manifested in prion diseases, is not an anomaly but the result of a general mechanism (Inge‑Vechomov, 2000). Thus, chaperone proteins participate in the synthesis of many polypeptide chains, determining their conformation. Even the cytoskeleton, which transmits features of the spatial organization of cellular structures, possesses inheritable capacity (Alberts et al., 1987, vol. 3, p. 132). Cultural inheritance in humans (and, to a lesser extent, in some other species) ensures the transmission of acquired traits and the shift to more efficient ways of generating adaptations. As shown in Fig. 1, the ES not only depends on hereditary determinants but also influences them. Examples of such influences on genetic inheritance are epigenes (Holubovskyi, Churaev, 1987), and on non‑genetic inheritance—dynamically inherited protein‑conformation changes. Experiments have demonstrated bacteria’s ability to remodel their genetic apparatus within the lifespan of a single cell, providing gene changes needed for growth on a particular medium (Holubovskyi, 2001). When flax was cultivated on a biogene‑enriched soil, hereditary changes arose that increased plant size (Marx, 1984). These facts may seem to align with T. D. Lysenko’s views. However, a principal feature of these results is that they were obtained in sound experiments and are free of ideological overtones. It is well known that a characteristic feature of a scientific paradigm shift is the reinterpretation of known facts. The epigenetic theory provides grounds for revising concepts such as gene, mutation, modification, driving selection, etc. (Shishkin, 1987). It is improper to equate Mendelian genes with chromosome‑localized cytrosomes. In fact, a Mendelian gene is a switch between two epigenetically stabilized trajectories of individual development, not the cause of their emergence. Contrary to common views, only two basic types of selection can be distinguished: stabilizing and destabilizing. Traits should be divided not into inheritable (genotypic) and non‑inheritable (phenotypic) but into stable and labile in their expression. Is the problem of purposiveness solved? The problem of biological purposiveness became a key issue for natural science already in Aristotle’s time. The notion that purposeful organisms arose by chance appeared in antiquity and was expressed in various forms by Empedocles, Epicurus, and Lucretius. Darwinism added to this the hypothesis of long sequences of small undirected changes that randomly increase organismal fitness. Modern nonlinear thermodynamics studies self‑organization as a consequence of random perturbations. Nevertheless, the idea that purposiveness arises from random deviations cannot be considered definitively proven. It is contradicted by the fact that mutations are usually deleterious and not integrated into the genotype. For scientists convinced of nature’s perfection, the idea of random emergence of purposiveness is unacceptable. Probably for this reason L. S. Berg postulated an immanent, scientifically unanalyzable purposiveness of the living (Berg, 1977). The epigenetic theory opens the possibility of a new solution to the problem of purposiveness, beyond Berg’s classification (ibid., pp. 99–101). The purposiveness of mutations postulated in STE is a phenomenon on the verge of a miracle. In contrast, aberrations caused by destabilization of normal development can be potentially purposeful, because their formation involves an ES shaped by the prior evolution of the species and life as a whole. A gene mutation is not linked to corresponding changes in other genotype elements; an epigenetic aberration can affect many traits while preserving their correlations. Mutations arise randomly, whereas aberrations appear when the former population norm ceases to be adaptive. Finally, as D. L. Hrodnytskyi (2001) notes, the regularity of aberrant phenotype emergence makes it sufficiently probable to encounter their carriers. If any arising aberration proves adaptive, a process modeled by Woodington’s experiments occurs in the population: selection for the stability of its reproduction across generations. The final stage is the stabilization of a new norm. Thus, a new trait passes through the following stages of its formation: a more or less adaptive “modification” developing under appropriate environmental influence; one of the alternative developmental pathways, increasingly stably realized in ontogeny; a norm whose development no longer requires specific external influences. To explain the appearance (often parallel in different organism groups) of complexes of mutually advantageous traits, one should consider the influence of a regulatory mechanism that lies above the level of individual hereditary determinants—the ES. This is precisely the way to overcome the “Jenkin’s nightmare.” P. Teyssier de Chardin (1987) claimed that life moves forward “by feel.” These words are usually understood as a statement of the inevitability of accumulating random errors. The analogy of Teyssier is probably much deeper. Although there is no predetermined final state in the evolutionary process, there is also no random tossing from side to side. The direction of each evolutionary step is determined by the whole organism’s response to changes in its environment. Ecological theory of evolution The reductionism characteristic of STE manifests not only in representing the developmental control system as a mosaic of genes but also in treating the population as the main theater of evolutionary events. Each biocenosis possesses a certain capacity to maintain homeostasis. Changes in external (e.g., climatic) factors can be compensated by internal regulatory mechanisms of that biocenosis. These mechanisms maintain the characteristic structure of ecological niches within a certain range of external conditions. At the same time, a stabilizing selection for normal development acts on populations, resulting in little change or slow, coherent evolution. V. A. Krasilov (1969) called evolution within a stable biocenosis coherent evolution. In the case of biocenosis breakdown, rapid incoherent evolution of its individual elements is observed. The most plastic and least integrated species in a disrupted community can persist under altered conditions. The cessation of stabilizing selection and the diversity of developmental conditions lead to ontogenetic destabilization and the expression of a variability reserve characteristic of the ES of those species. In unstable communities, r‑strategists gain an advantage. r‑selection results in accelerated individual development, which may lead to partial loss of specialization achieved in the later stages of ontogeny. Mosaic patches of territory at different successional stages and forming new biocenoses facilitate quantum evolution. Thus, in anthropogenically altered biocenoses, rapid emergence of adaptive traits has been recorded in several species (e.g., new forms of avian nesting behavior or simplification of the life cycle of migratory fish). The epigenetic theory does not address why selection begins to support one aberration rather than the former norm. Ecological theory explains the stepwise change in the character of selection. Both concepts focus on the holistic properties of the studied systems and complement each other well. Concept of species monomorphism It is interesting to compare the conclusions of the epigenetic theory of evolution with data on the existence of a monomorphic complex of genetic and physiological traits in species. “One of the most important properties of the eukaryotic genome is the duality of its structural‑functional organization, directly reflected in the coexistence of two real phenomena: polymorphism and monomorphism” (Altuho, 1989, p. 219). Intraspecific monomorphism is characteristic of genetic systems with many structural components and high redundancy (ibid., p. 203), i.e., of the regulatory part of the genome. Similarly, H. Carson distinguishes two systems of genetic variability: an “open” system represented by loci that provide intraspecific polymorphism, and a “closed” system associated with co‑adapted gene blocks (Carson, 1982). From this viewpoint, speciation is a consequence of reorganization of the “closed” part of the genome. D. K. Belyaev (1974) showed that destabilizing selection on certain traits leads to the manifestation of wide variability in other previously stable traits. This phenomenon may be linked to reorganization of the “closed” genome part and the ES. Study of genome variability leads to a conclusion fully consistent with the epigenetic theory: “At the supra‑specific level, evolution is not only, or rather not so much, the appearance of new genes with new functions, but a rapid reorganization of genetic material followed by the development of new systems of gene interaction (and regulation) at the post‑transcriptional and post‑translational levels” (Altuho, 1989, p. 216). S. S. Schwartz showed that “adaptations of specialized species and adaptations of individual populations of widely distributed species proceed by fundamentally different routes” (1980, p. 45). Adaptations of intraspecific forms to changing environmental conditions are expressed in morphofunctional shifts (changes in heart or kidney size, blood oxygen‑binding capacity, etc.). Species‑level adaptations occur at tissue and biochemical levels, making morphofunctional shifts unnecessary. The integrity of a species, besides genetic mechanisms, is supported by species‑specific responses to environmental changes (ibid., p. 132), which can also be viewed as a reflection of the commonality of the ES. Some traits, demonstrating differences among various taxa, turn out to be monomorphic within most of them (thus resembling species traits linked to the “closed” genome part and the ES). For example, all mammals have erythrocytes of the same size, different from those of birds, reptiles, fish, and caecilian amphibians. The only vertebrate group in which a substantial diversity of erythrocyte sizes has been recorded is the tailed amphibians (Schmidt‑Nielsen, 1987, p. 128). Probably, within a third synthesis it will be necessary to abandon the STE‑typical gradualism (derived from the view that adaptation arises from randomly beneficial mutations). One may assume that it will delineate periods of stabilization and destabilization of the developmental control system. It is reasonable to hypothesize that the monomorphic part of the species genome underlies the species‑specific ES. Occupation of a new adaptive zone, emergence of taxa of a given level, will most likely occur as a result of restructuring the main characteristics of the ES. In this context, the epigenetic concept of species proposed by K. E. Mykhailov in a work published on the Internet (Mykhailov, url) is of interest. According to this concept, the main characteristic of a species is a stabilized ontogeny. With this approach, populations and individuals that are in the transitional phase of speciation during ontogenetic destabilization should be regarded as deviant forms, close to one species but not belonging to it. Extending Mykhailov’s views, the presence of stabilized epigenetic creodes could be included in the characterization of supra‑specific taxa. An unexpected consequence of this approach could be the justification for recognizing transitional groups that do not belong to taxa of higher ranks, i.e., incertae sedis forms (for example, families not assigned to any order of their class). Neo‑saltationism and punctuated equilibrium One possible route of genome reorganization is chromosomal rearrangements (Altuho, 1989; Vorontsov, 1999). A close link between genome reorganization and hybridization is probable (Borkin, Darevsky, 1980). In recent decades, numerous confirmations of the significance of punctuated events for evolution have been obtained, reviving interest in saltationism, seemingly refuted by the modern synthesis. Karyotype studies of closely related species have shown the important role of chromosomal rearrangements and polyploidy in speciation not only in plants but also in animals (including highly progressive groups such as frogs and rodents). This allows the assumption that, in many cases, the emergence of partial or complete isolation precedes ecological or morphophysiological differentiation (Vorontsov, 1999). In such a case, competitive exclusion of karyologically isolated forms should promote their divergence. Examples of fairly well‑studied saltational events can be given. A strain of *Clostridium botulinum* causing botulism, when infected with a specific phage, transforms into *Clostridium novyi*, the agent of gas gangrene (Eklund et al., 1974). During the emergence of several mammalian orders, fixation of aberrations such as hairlessness, pug‑like morphology, and papillomatosis occurred (Vorontsov, 1999, pp. 507–507). One enzyme (Cu‑Zn superoxide dismutase) of the bioluminescent bacterium *Photobacterium leiognathi* resembles not the analogous enzymes of prokaryotes but those of silver‑belly fishes (Leiognathidae), symbionts of these bacteria. This indicates a “horizontal transfer” of hereditary information (ibid., p. 518). Alteration of hormonal balance by adding thyroxine induces in the mudskipper (*Periophthalmus*) a ontogenetic remodeling that includes development of “limbs” instead of pectoral fins (Harms, 1934). According to molecular systematics data, the major animal groups arose through successive endosymbioses (Kusakin, Drozdov, 1994)—punctuated evolutionary events. Finally, some evolutionary events (e.g., the origin of secondary‑jawed animals from primary‑jawed ones, the connection of the olfactory canal with the oral cavity by hoans in fish) could not have occurred gradually. The presented and other facts demonstrate the inadmissibility of the STE‑typical reduction of macroevolution and speciation to microevolution. Neo‑saltationism, like the epigenetic and ecological theories, explains the uneven rates of evolution on which the concept of punctuated equilibrium is based. The possibility of exploiting a new adaptive zone may arise as a result of various saltational events. These include substantial changes in developmental trajectories due to macro‑mutations, acquisition of an adaptive trait via horizontal transfer, or a whole complex of traits through hybridization (Borkin, Darevsky, 1980), introgression, or symbiogenesis. Further evolution of the developmental control system will proceed under the influence of selection stabilizing some of the new developmental variants. Increasing efficiency of the evolutionary process From the STE perspective, the speed of evolution should decrease as the genetic system of organisms becomes more complex and their generational turnover slows. This is contradicted by the fact that evolutionary rates accelerate with increasing morphophysiological complexity of organisms. A striking episode in Earth’s history is the so‑called “Cambrian explosion”: the rapid emergence of the overwhelming majority of animal types that ever existed, many of which soon became extinct. It is hard to attribute this event to small undirected population‑genetic changes.It is more likely that it is caused by the emergence of mechanisms that substantially increase the efficiency of macroevolution. For example, this could have been the acquisition by organisms of bilateral body symmetry, which is linked not so much to the acquisition of corresponding genes as to the development of epigenetically regulated variants of cell, tissue, and organ development responsible for the differentiation of body parts. The stabilization by selection of the most successful body plans should have been preceded by a wide variety of their variants. Currently, a well‑regulated epigenetic complex governs the body plan, and significant novelties are not observed in modern organisms. As I. I. Shmalgauzen noted, the consequence of inter‑group selection is the displacement of forms that lag in the rate and quality of adaptation to a changing environment. Such a process should lead to the improvement of the evolutionary mechanism itself (Shmalgauzen, 1968; Zavadsky, Kolchinsky, 1977). The acceleration of evolution in highly organized forms (Rasnitsyn, 1978) is the result of such inter‑group selection.

Apparently, as organisms become more complex, the epigenetic component plays an increasingly important role in shaping their traits. The biochemical traits of prokaryotes are determined mainly at the genetic level (this is widely used in genetic engineering). In contrast, the morphological traits of highly developed organisms depend on a complex system of epigenetic interactions. The existence of mechanisms that ensure species integrity and manifest in species monomorphism may also be a consequence of “the evolution of evolution”.

The efficiency of evolution in many species is enhanced by the subdivision of their population structure (Konovalov, 1974; Altuhoh, 1989). Thus, even on a relatively homogeneous territory, green toads (Bufo viridis) and common toads (B. bufo) form local groups that differ in many traits more strongly than subspecies or closely related species (Shabanov, 2001, 2002). A large number of diversity levels, most of which can be subject to group selection (Shabanov, Shabanova, 2001), increases its effectiveness.

Consequently, there are grounds to assume that the main evolutionary pathway is the refinement of epigenetic mechanisms regulating individual and historical development. Therefore, the efficiency of epigenetic system restructuring under selection may serve as a measure of evolutionary progress for particular groups. The most important milestones of this path are the development of regulation of bacterial cistron expression; the emergence of sexual reproduction; the formation of multicellular organisms; the appearance of a cultural inheritance mechanism.

**Some Conclusions** Based on the foregoing, several conclusions can be drawn.

Some conclusions Based on the foregoing, several conclusions can be drawn. 1. Our time is a period of crisis of the second evolutionary synthesis (SES) and the formation of a third synthesis. This synthesis is intended to describe the pathways of emergence of adaptive complexes of traits, the action of factors that direct evolution and regulate its rate, and the historical refinement of evolutionary mechanisms.

2. A distinctive feature of the third synthesis should be a systems approach to evolution, its study at different levels with the identification of integrating mechanisms for each of them.

2. The distinctive feature of the third synthesis should be a systems approach to evolution, its study at various levels with the identification of integrating mechanisms for each. 3. The third synthesis should unite the achievements of various relatively independent concepts (classical Darwinism, biology of individual development, modern genetics, M. A. Shishkin’s epigenetic theory, V. A. Krasilov’s ecological theory, neosaltationism, concepts of species monomorphism, “evolution of evolution”, punctuated equilibrium, and others).

4. The notion of punctuated speciation is consistent with data on genome reorganization during species emergence and species monomorphism. Ecological and epigenetic theories, as well as neosaltationism, explain the causes of uneven evolutionary rates, while the punctuated equilibrium concept focuses on its outcomes.

5. M. A. Shishkin's epigenetic theory emphasizes the key level of ontogenesis regulation. One of its consequences is a new approach to solving the problem of the emergence of biological purposefulness.

5. M. A. Shishkin’s epigenetic theory emphasizes a key level of ontogenetic regulation. One of its consequences is a new approach to solving the problem of the emergence of biological purposiveness. What data could confirm the views expressed here? The hypothesis that ontogeny of individuals developing under controlled conditions from disturbed (including anthropogenically impacted) ecosystems would be less stable than that of individuals from reference habitats is testable.

To support the epigenetic theory, it would be useful to test the hypothesis that Mendelian alleles are not nucleotide sequences but switches set by the entire epigenetic system between stabilized norm variants. For this, their experimental acquisition and disruption should be carried out. Suppose that, under selection in a destabilized population, carriers of both alternative aberrations are retained. Will such selection produce Mendelian epigenetic switches of ontogeny? Will this process be more effective under cultivation conditions that differ substantially from normal ones (e.g., when raising Drosophila on a non‑standard medium)? Will selection for stable reproduction of a heterozygous phenotype (arising from crossing lines with different stabilized norm variants) lead to the cessation of its Mendelian segregation? One variant of such selection is the preservation of heterozygous phenotype carriers from those broods where their proportion was maximal.

Some statements of this article can be examined by studying the variability of the monomorphic part of the genome in experimental populations subjected to strong selection for a shift in adaptive norm.

The main goal set by the author was to stimulate discussion and experimental investigation of the issues raised.

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