[Epigenetics: gene and epigene networks in ontogeny and phylogeny].

An attempt was made to systematize theoretical and experimental epigenetic data in the framework of genetics as a science on laws of preservation, coding, transfer, and transformation of heritable information in the living systems. The structure of the total hereditary memory is discussed in context of the theory of epigenes, hereditary units of the next to genes level of complexity. In epigenes as cells of functional hereditary memory, part of the hereditary information is stored, coded, and transmitted to the progeny irrespective of the primary structure of the genomic DNA molecules. The principles of the structure and the general laws of functioning of cellular governing gene networks are presented. The ontogenetic and phylogenetic role of epigene networks as the second level of the hereditary system is considered. Arguments for inheritance of somatic epimutations are presented, as well as the results of in silico and in vivo experiments showing the possibility of an epigenetic mechanism of primary biochemical divergent determination (autodetermination). A network hypothesis on material carriers of the common heterotary memory is formulated.

[The frame of non-canonical theory of heredity: from genes to epigenes].

Particular theory of heredity that exceeds the limits of mendelian genetics is suggested. The model based on five sufficiently obvious assumptions (accepted as axioms) As consequence of these axioms the strict statements concerningfunctional heredity memory were formulated in mathematical terms. Molecular-genetic realization of the memory cells appears as new class of heredity units--epigenes. In the epigenes part f hereditary information is contained, encoded and transmitted beyond the primary structure of DNA molecules of genome. Epigenes capable to conserve sequences of genes functional states in the course of ontogenesis and provide transmission of information contained in this states throw consequent generations. It was shown that epigenes differ from genes at least by encoding method of heredity information. There are three functional-equivalent classes of really existing epigenes mechanisms: dynamic, modificational and transpositional; and there is one hypothetical class--invertional. It was shown that a lot of experimental data concerning epigenetic mechanism of heredity is in accord with theoretical conclusions concerning epigenes existence. Moreover, we constructed an artificial epigenes by genetic engineering methods. The existence of epigenes means that obtaining complete genome sequence, its physical and genetic maps, as well as distinguishing the rules of genes function encoding by its primary structure do not provide complete decoding of hereditary information. The role of epigenes in ontogenesis and phylogenesis was examined. It was shown that even elementary epigenetic systems could determine key ontogenesis events. Epigenetic system could serve as the basis of non-darwinian evolutionary strategies by means of "memorization of rather unsuccessfully steps of evolution" and conservation of alternative variants of ontogenesis. Teleonomic hypothesis on functional heredity memory was formulated. This theory provides explanation of phenomena of acquired features inheritance and molecular mechanisms of stress-induced evolution.

[On parametric stability of gene networks controlling ontogenetic processes]. / O parametricheskoi ustoichivosti gennykh setei, upravliaiushchikh ontogeneticheskimi protsessami.

The problem of evaluating the parametric stability of three models of pro- and eukaryotic gene networks controlling ontogenetic processes has been defined and solved. Experimental plans of testing gene networks for parametric stability based on the method of generalized threshold models were developed and realized as a software application. We examined the "sensitivity" of the functioning modes to random variations of the parameters in the three model systems: the system of developmental control of phage lambda, the subsystem of morphogenetic control of Arabidopsis thaliana flower, and the gene subnetwork controlling early ontogeny in Drosophila melanogaster. The parametric stability was quantitatively assessed for these models.

[Construction of an artificial digenic network with epigenetic properties]. / Konstruirovanie iskusstvennoi digennoi seti, obladaiushchei épigeneticheskimi svoistvami.

A model of the simplest epigene was constructed to have two alternative states, which proved to be stable and transmittable through Escherichia coli cell generations. A switch from one to another state was induced by thermal and chemical external signals. The results gave further insight into the dynamic mechanism of preservation, coding, and transmission of the genetic information.

[Modeling real eukaryotic control gene subnetworks based on generalized threshold models]. / Modelirovanie real'nykh éukarioticheskikh upravliaiushcheikh gennykh podsete na osnove metoda obobshchennykh porogovykh modelei.

Mathematical and computational means are developed that take into consideration the specifics of control processes at the molecular level and allow one to obtain both qualitative and quantitative patterns of gene network dynamics. Using the method of generalized threshold models, models are constructed for the Arabidopsis thaliana flower morphogenesis control subsystem and gene subnetwork controlling the Drosophila melanogaster early ontogeny. The dynamics of these systems are investigated: kinetic curves are computed for molecular components (RNA, proteins), possible modes of functioning and steady states of the nets are revealed and biologically interpreted. The models are shown to be adequate to the real processes. The effectiveness of the generalized threshold model method is evaluated in the analysis of the actual eukaryotic gene networks.

[Expanded model of lambda phage ontogeny]. / Rasshirennaia model' ontogeneza faga liambda.

An enlarged threshold model of regulatory system of development of lambda phage (RSDP lambda-2) is built. It includes 15 synthetic blocks of proteins and mRNAs and 4 blocks corresponding to the ontogenetic processes: two-stage replication, integration and exclusion of phage genome, formation of aggregates of regulatory proteins, regulation of bacterial lysis. By means of computer simulation of the RSDP lambda-2 model, the dynamics of concentrations of all main proteins, respective fractions of mRNAs and DNA are described in lytic and lysogenic regimens of phage ontogenesis. The results obtained are in a good agreement with available experimental data. The dependence of portion (%) of lysogenic responses on the mean multiplicity n of phage infection of bacterial culture, is built. This curve has a maximum point in accordance with experimental data of Kourilsky [10].