Introduction by Eugene Daev

Since the very beginning, I suggested that state of stress, which accompanied by sharp hormonal changes (Selye, 1950), ought to have an effect at the genetic level.

My group has focused on pheromonal destabilization of mouse genome. We used the urinary pheromones from conspecific males and/or females as sex-specific stressors.

Cytogenetic pheromonal effects we discovered supported this idea. We showed the genetic effects (mutagenic and antimutagenic) in vital peripheral organs (bone marrow and germ cells) in mice after sniffing pheromones. Therefore, our group interpreted these effects to be signs of stress at genetic level. Now it is easier to understand how pheromones act.

Effects on hormones appear to be linked to affects of hormones on behavior, physiology and genetics of the organism in the following sequence of events: pheromones – “reception – perception” in brain – spread to the periphery. The sequence requires an epigenetic effect that (in case of psychosocial stressors) begins with gene activation in brain cells, which link gonadotropin releasing hormone (probably not only) pulse frequency to changes in the levels of other hormones which in turn regulate intracellular messenger activity. This leads to changes of activity and stability of organized genomes in targeted cells.

Thus, organisms that cannot adapt to the stressors are examples of targeted cell type destruction. Organisms that epigenetically adapt, exemplify the link from non-lethal stressors to adaptation in their phenotypes. The adapted phenotypes appear to be more resistant to stress, and adaptations protect adapted organisms from stress-induced mutations.

Density-dependent pheromonal regulation of rate of mutations and following specific cell selection inside the organism is the model, which helps understanding the mechanism (at least in rodents) of self-regulation of population density and rate of microevolutionary changes.

My summary of his introduction:

His works focus on stress-linked hormonal changes that link genes and behavior.  For instance, Selye considered “Stress in heath and disease is medically, sociologically, and philosophically the most meaningful subject for humanity that I can think of”. Professor Daev’s group uses the urinary pheromones from conspecific males and/or females as sex-specific stressors. They discovered and reported cytogenetic effects of pheromones, which supported their hypothesis.

In a series of published works, they showed mutagenic and antimutagenic changes in vital peripheral organs (bone marrow and germ cells) in mice after sniffing pheromones. Their group interpreted these changes in the context of genetic stress. The interpretation may help others to understand the dynamic interactions that link social stress from pheromones to genes and behavior in the context of healthy longevity or to pathology.

Effects on hormones appear to be linked to affects of hormones on behavior. The effects and affects link physiology from metabolic networks to genetic networks via the following sequence of events: pheromones – “reception – perception” in brain. That sequence links the effects and affects of pheromones to the cell type differentiaton in the periphery. The sequence requires an epigenetic effect that (in case of psychosocial stressors) begins with gene activation in brain cells, which link gonadotropin releasing hormone (and perhaps other hormones) from pulse frequency to changes in intracellular messenger activity. Those changes lead to differences in the activity and stability of organized genomes in targeted cells.

Organisms that cannot adapt to the stressors become examples of targeted cell type destruction. Organisms that epigenetically adapt, exemplify the link from non-lethal stressors to adaptation in their morphological and behavioral phenotypes. The adapted phenotypes appear to be more resistant to stress, and adaptations protect adapted organisms from stress-induced mutations.

The group has modeled density-dependent pheromonal regulation of rate of mutations and tracked specific cell selection inside the organism. The model attests to what appear to be conserved molecular mechanisms (at least in rodents) of self-regulation of population density and rate of microevolutionary changes.

In my works, the term “abiotic environmental stressor” can be placed into the context of olfactory receptor gene creation and virus-driven loss of function in genes. Loss of function is linked to the entropy of organized genomes, which is how mutations are linked to pathology.

Eugene V. Daev: Chronology

* indicates a reference to a published work or a presentation that I have not yet seen.

Research Gate requires an institutional address for access to published works or to follow researchers. That prevents anyone outside academia from viewing documents that are available for free.

The alternative is to contact Professor Daev and ask for reprints.  I have provided links to some of the abstracts available from the PubMed database, which falsely indicates that many publications are only available in the Russian language.  That misrepresentation also prevents many people from requesting reprints of articles that Professor Daev will send.

This chronology attests to the importance of learning who else has been linking atoms to ecosystems via what is now known to all serious scientists about biologically-based cause and effect. Like Bruce McEwen, and Anna Di Cosmo, Eugene Daev has made a series of important contributions that help to explain the role of pheromones in RNA-mediated cell type differentiation.

When placed into the context of how the microRNA/messenger RNA balance and RNA-mediated amino acid substitutions differentiate the cell types of all individuals of all living genera, Professor Daev’s works link metabolic networks and genetic networks via the cytogenetic effects of house mouse pheromones and the physiology of reproduction. Thus,  ecological variation in the availability of nutrients that are metabolized to species-specific pheromones can, like food odors, also be linked via social stress to ecological adaptation without the pseudoscientific nonsense of neo-Darwinian theory.

Any news source that wants to prevent the dissemination of accurate information about biologically-based cause and effect need only exclude works like these by people like Eugene Daev.

Here are some examples of what you may not otherwise see. Most publications are available from author in English upon request to Professor Daev via email to: mouse_gene@mail.ru

Note, for example, that all crustaceans were linked to all insects in a report on the 2015 Society for Integrative and Comparative Biology meeting. All in the (bigger) family.

See also: Desires of Microscopic Shrimp Illuminate Evolutionary Theory

Excerpt:

“I’ve always been interested in speciation and how species form, but this is a whole different mechanism, that light can influence speciation,” Ellis says. “I thought it was just fabulous.”

My comment: The idea that conserved molecular mechanisms link light to speciation is not new, see What is Life (1944). That suggests Ellis and other SICB 2015 meeting attendees/members may benefit from step-by-step recommendations for the analysis of cytogenetic data in the most recent report from Professor Daev’s group:

Daev EV, Dukelskaya AV, Barabanova LV 
Russian Journal of Genetics. 2015; 5(5): 441-448.
DOI: 10.1134/s2079059715050056
Abstract excerpt:
We present a step-by-step recommendations for the analysis of the cytogenetic data and discuss the prospects of applying genetic tests for ecological monitoring, based on the example of analysis using crustacean species.

Antimutagenic effect of chemosignals from isolated female house mouse on male germ cells (Mus musculus L.)
Daev EV, Bezruchko YA, Dukelskaya A.V.
Russian Journal of Genetics. 2014; 50(6): 621–625.
DOI: 10.1134/S1022795414060027

Conclusion:

Unfortunately, the problem of how the different states of the integrated neuroendocrine immune system can themselves have mutagenic/antimutagenic effect on the reproductive cells of the same organism is still to be investigated. Studies on how external signals can specifically tune the nervous system so that it would be capable of increasing the resistance of the genetic apparatus of the germ cells to radiation and other mutagenic factors would undoubtedly be promising. This would allow future development of noninvasive approaches to stabilization of the genetic apparatus in germ cells of human being via the psychoemotional state of any individual’s nervous system.

Chemosignals from Isolated Females Have Antimutagenic Effect in Dividing the Cells of Bone Marrow from Male Mice of the CBA Strain.
Daev EV, Glinin TS, Dukel’skaya AV.
Russian Journal of Genetics. 2014; 50(1): 55–60.
DOI: 10.1134/S1022795414010037

Conclusion:

Humans also have various pheromone-induced physiological effects, especially those associated with reproduction [46, 47]. This suggests that the human olfactory system is still an effective pathway for influencing environmental factors on the human nervous system. Various psychoemotional states of the human nervous system can, in turn, disrupt the integrity of the chromosomal apparatus of target cells, for instance lymphocytes [41, 42]. Therefore, studies on the oppositely directional modulation of the mutagenic consequences of stress in rodents with the use of specific, volatile, and zoosocial important chemosignals are a promising approach both to modeling posttraumatic stress disorders in humans [36] and to searching for mehods of their treatment.

Effect of two pyrazine-containing chemosignals on cells of bone marrow and testes in male house mice (Mus musculus L.)
Daev EV, Vyborova AM, Kazarova VÉ, Dukel’skaya AV.
Journal of Evolutionary Biochemistry and Physiology. 2012; 48(1): 18—23.
DOI: 10.1134/S0022093012010033

Conclusion:

…The ana-telophase analysis thus detects both “strong” and “weak” (or “delayed”) effects of CMP. As to the metaphase analysis, it reveals only the “strong” effect of the pheromone 2,5-DMP that has already become apparent as structural chromosome aberrations.

It is to be noted that the effect of both chemosignals was revealed in the sperm head anomaly test in male CBA mice (see table): the impact of 2,5-DMP as well as CMP on the olfactory system of the recipients increased frequency of the malformed mature spermatozoa heads in the cauda epididymidis on the 17th day after the 24-h exposure. Taking into account the differentiation rate in the reproductive cells [23, 24], it suggests that meiotically dividing spermatocytes are also the target for the effect of the studied chemosignals mediated by the central nervous system. The induction of genetic instability leading to a higher genetic heterogeneity in cells of vital tissues and organs may differentially change the fitness of animals and their progeny. Such olfactory effects can affect rates of microevolutionary transformations [5].

With regard to the conservatism and the significant role of the chemical communication in a wide range of mammals, including Homo sapiens [25], we believe extremely promising the study of genetic mechanisms underlying regulation of reproduction and immunity by volatiles that work through the olfactory system.

The role of metabolic activation of promutagens in the genome destabilization under pheromonal stress in the house mouse (Mus musculus)
Zhuk AS, Stepchenkova EI, Dukel’skaya AV, Daev EV, Inge-Vechtomov SG.
Russian Journal of Genetics. 2011; 47(10): 1209–1214.
DOI: 10.1134/S102279541110019X

Conclusion:

Thus, the results of this study confirm our hypothesis that the increase in the frequency of mitotic disturbances in the mouse bone marrow under olfactory stress is accompanied by changes in the activities of enzymes of the cytochrome P450 family in the liver.

Stress-induced mutagenesis may be mediated by altered activity of p450 cytochrome in mice.
Zhuk AS, Stepchenkova EI, Dukel’skaya AV, Daev EV, Inge-Vechtomov SG.
In: Crimean Meeting: 3rd International Conference “Modern problems of Genetics, Radiobiology, Radioecology and Evolution” & NATO Advanced Research Workshop “Radiobiological Issues Penetrating to Environmental Security and Ecoterrorism”: Abst., Papers by Young Scientists. 2010. Dubna: JINR. P. 175-177.
ISBN 978-5-9530-0252-3

The role of social factors in the regulation of stability of the cell genetic machinery in animals.
Daev EV, Glinin TS, Dukelskaya AV.
Dokl Biochem Biophys. 2010; 435:299-301.
DOI: 10.1134/S1607672910060050

Stress, chemocommunication, and the physiological hypothesis of mutation.
Daev EV.
Russian Journal of Genetics. 2007; 43(10): 1082–1092. Review.
DOI: 10.1134/S102279540710002X

Conclusion:

The data surveyed in this review support the physiological hypothesis of mutation [40, 57]. They also demonstrate that, increasing the genomic variability in germline cells (at least in male house mice), stressors provide material for natural selection and promote qualitative changes in the progeny of stressed animals. The fertility of stressed animals markedly declines [83, 95]. At the same time, stress results in changing the variability of bone marrow cells, which seem to be fairly sensitive to pheromonal (stress) factors. This may
reflect on the processes of hemato- and immunopoiesis, e.g., increase the frequency of lymphoproliferative diseases, decrease infection resistance, etc.

The pheromone concentration in the environment increases with the population density. Their qualitative composition also changes, i.e., synthesis of additional active pheromones (e.g., 2.5 DMP) begins. Chromosome aberrations are induced in male germ cells, reducing fertility of these males. Immunity and general fitness of the animals reduce. On the other hand, pheromonal stress increases the genetic diversity of the survived progeny, while the reduction in number creates a bottleneck. Thus, conditions appear for divergence and change in genetic structure of the future house mouse populations. Different strain types point to the arising genetic differences in the survived ani mals, which switch on a microevolutionary process. A stress-induced reduction in general fitness and fertility of the animals in natural population may result in a bottleneck, and genetic heterogeneity of germline cells may mediate an increase in genetic variation of the progeny (Fig. 4). Finally, this may act as a mechanism of acceleration of microevolutionary change upon dramatic changes in the environment [83, 92, 98].

Induction of dominant lethals in progeny of CBA male mice after pheromonal action.
Daev EV.
Russian Journal of Genetics. 2003; 39(10): 1138–1142.

The female pheromone 2,5-dimethylpyrazine induces sperm head abnormalities in male CBA mice.
Daev EV, Dukel’skaya AV.
Russian Journal of Genetics. 2003; 39(7): 811–815.

Analysis for pheromone-induced cytogenetic disturbances depending on major urinary proteins of male laboratory mice.
Daev EV, Sverdlova OL.
Russian Journal of Genetics. 2002; 38(2): 132–137.

Cytogenetic effect of volatile components of urine of mature animals on bone marrow cells of young female house mice Mus musculus L.
Daev EV, Poluekhina EV.
Russian Journal of Genetics. 1996; 32(3): 357-360.

Cytogenetic effects of pheromones on bone marrow cells of male house mice Mus musculus L.
Daev EV, Sverdlova OL, Matskevich OA, Antoniuk EV.
Russian Journal of Genetics. 1995; 31(5): 541-544.

Pheromonal Regulation of Genetic Processes: Research on the House Mouse (Mus musculus L.)
Daev EV
Russian Journal of Genetics. 1994; 30(8): 964 – 970.

Conclusion: 

The specificity of pheromonal regulation depends on such significant characteristics as population den¬sity and population structure (age and genetic). Along with other conditions, it defines the reproductive status of individuals and, possibly, not only the quantity, but also the quality, of the progeny. If this proposition is true, then this mechanism can determine the spatial genetic structure of the future population and the speed of alteration of this structure [66, 67]. We suppose that similar systems of intraorganism regulation of genetic processes can exists in other animal species. Their detection and study is a new and promising direction of research for the understanding of the regularities of functioning of genetic material on organismal and interorganismal levels of organization.

Frequency of dominant lethals in progeny of young male house mice (Mus musculus) after exposure to excretory products of adult males of the same species (1988). [Incidence of dominant lethals in the progeny of young male house mice (Mus musculus L.) after exposure to excretory products of mature males of the same species]. Daev EV, Tsapygina RI, Lopatina NG.
Plenum Publishing Corporation. 1989: 1409-1414 (translated from: Genetika. 1988; 24(11):2015-21).

——————–

*The Response of Bone Marrow and Spleen Immunocompetent Cells of Mouse Males of Different Strains to Stress and Pyrazine-Containing Chemosignals.
Daev EV, Surinov BP, Dukel’skaya AV.
Russian Journal of Genetics: Applied Research, 2013, Vol. 3, No. 5, pp. 412–417.
DOI 10.1134/S207905971305002X

*Pheromones and adaptive bystander-mutagenesis in mice.
Daev EV, Glinin TS, Dukel’skaya AV.
In: Radiobiology and Environmental Security (Eds., Mothersill C.E., Korogodina V., Seymour C.B.), 2012. Dordrecht (Netherlands): Springer. P. 153-161.
DOI 10.1007/978-94-007-1939-2_14

*The Balance Hypothesis of the Effect of Socially Important Volatile Chemosignals on Reactivity of Chromosome Machinery of Bone Marrow Dividing Cells in the House Mouse Mus musculus.
Daev EV, Glinin TS, Dukel’skaya AV.
Journal of Evolutionary Biochemistry and Physiology, 2012, Vol. 48, No. 3, pp. 280—286.
DOI 10.1134/S0022093012030048

*Genetic Aspects of Stress Neuroendocrinology.
Daev EV.
In: Neuroendocrinology Research Developments (Eds. N. S. Penkava and L. R. Haight). Hauppauge, New York: Nova Science Publishers, Inc., 2010. P. 119-133.

*Effects of “Pheromone-Like” Pyrazine-Containing Compounds on Stability of Genetic Apparatus in Bone Marrow Cells of the Male House Mouse Mus musculus L.
Daev EV, Kazarova VE, Vyborova AM, Dukel’skaya AV.
Journal of Evolutionary Biochemistry and Physiology. 2009; 45(5): 589-595.
DOI: 10.1134/S0022093009050053

*Effect of the Estrus Cycle Stage on Sensitivity to Pheromone 2,5-Dimethylpyrazine in the House Mouse Mus musculus.
Daev EV, Dukel’skaya AV, Kazarova VE, Filkina YA.
Journal of Evolutionary Biochemistry and Physiology. 2007; 43(6): 573-578.
DOI: 10.1134/S0022093007060059

*Immunological, Cytogenetical, and Behavioral Changes in CBA and C57BL/6 Male Mice after Pheromonal Action.
Daev EV, Surinov BP, Dukel’skaya AV, Karpova NA, Kulish YS, Isaeva VG.
Journal of Evolutionary Biochemistry and Physiology. 2005; 41(4): 398-405.
DOI: 10.1007/s10893-005-0075-6

*Genotype-specific changes in functional parameters of immunocompetent cells in laboratory male mice under conditions of pheromoneal stress.
Daev EV, Vorob’ev KV, Shustova TI, Zimina SA, Samotokin MB.
Russian Journal of Genetics. 2000; 36(8): 872-876.

*Recent biochemical insights into puberty acceleration, estrus induction and puberty delay in the house mouse.
Novotny MV, Ma W, Zidek L, Daev EV.
In: Advances in Chemical signals in Vertebrates 8. 1999. N.Y. :Kluwer Academic/Plenum Publishers. P. 99-116.

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