The template RNAs of RNA polymerases can have compact secondary structure, formed by long double helices with partial violations of the complementarity.

A new method of contextual analysis was used to search the long non-random inverted repeats and the complementary palindromes in the genes of E. coli and T7 RNA polymerases. These genes were found to contain from 25% to 50% of all the nucleotides involved in such helices. The 5' -and 3' -ends of mRNA can be protected by neighbouring double helices from the nuclease attack. Some double helices are competing and very similar to the attenuator of E. coli trp-operon.

[A concept of limiting genetic factors of expression, organization, and evolution]. / Kontseptsiia limitiruiushchikh geneticheskikh faktorov ékspressii, organizatsii i évoliutsii.

Elicitation and analysis of limiting genetic factors represent convenient method for approximate description of complex molecular-genetic systems. In sequential metabolic ways, the limiting is based on the minimum of catalytic activity, in parallel ones--on the maximum activity. In polygenic systems, the expressing polygenes affect always the limiting oligogenes. Limiting genes are only available to selection on the population level, the non-limiting genes being neutrally evolving. This result eliminates the acuteness of the Haldane's dilemma. The complex genetic systems could be quickly evolving by relay-race principle with sequentional change of limiting genes and without violation of Haldane's dilemma. The limiting factors of organization which restrict the possibilities of some special evolutionary directions have the key role in evolution. These limits were historically overcome by acceptance of evolutionary acquirements of wide usage. The sequence of such limits and acquirements was assumed as a basis of "scenario" of Prebiological and Biological Molecular Evolution. The concept is illustrated by some examples and results of theoretical analysis.

[The genetic language: grammar, semantics, evolution]. / Geneticheskii iazyk: grammatika, semantika, évoliutsiia.

The genetic language is a collection of rules and regularities of genetic information coding for genetic texts. It is defined by alphabet, grammar, collection of punctuation marks and regulatory sites, semantics. There is a review of these general attributes of genetic language, including also the problems of synonymy and evolution. The main directions of theoretical investigations of genetic language and neighbouring questions are formulated: (1) cryptographic problems, (2) analysis of genetic texts, (3) theoretical-linguistic problems, (4) evolutionary linguistic questions. The problem of genetic language becomes one of the key ones of molecular genetics, molecular biology and gene engineering.

[Comparative hierarchic structure of the genetic language]. / Sravnitel'naia ierarkhicheskaia struktura geneticheskogo iazyka.

The genetical texts and genetic language are built according to hierarchic principle and contain no less than 6 levels of coding sequences, separated by marks of punctuation, separation and indication: codons, cistrons, scriptons, replicons, linkage groups, genomes. Each level has all the attributes of the language. This hierarchic system expresses some general properties and regularities. The rules of genetic language being determined, the variability of genetical texts is generated by block-modular combinatorics on each level. Between levels there are some intermediate sublevels and module types capable of being combined. The genetic language is compared with two different independent linguistic systems: human natural languages and artificial programming languages. Genetic language is a natural one by its origin, but it is a typical technical language of the functioning genetic regulatory system--by its predestination. All three linguistic systems under comparison have evident similarity of the organization principles and hierarchical structures. This argues for similarity of their principles of appearance and evolution.

[Computer system for simulating population dynamic patterns of polygenes and mobile genetic elements upon truncation selection for a quantitative trait]. / Komp'iuternaia sistema dlia modelirovania populiatsionnoi dinamiki patternov poligenov i mobil'nykh geneticheskikh élementov pri otsekaiushchem otbore po kolichestvennomu priznaku.

A computer system was developed for simulation of population dynamics of interacting polygene patterns and mobile genetic elements (MGEs) under selection for a quantitative trait. The system is stochastic (Monte Carlo) and takes into account the main sources of random change in the patterns (recombinations, transpositions, excisions), genetic drift, and determined trends of selection and other genetic processes in a finite population. Using this model, it is possible to analyze the dynamics of many population parameters that cannot be experimentally estimated: frequencies of polygenic alleles, proportions of adaptive and random fixations, average heterozygosities of polygenes and MGEs, coefficient of inbreeding, heritability, etc. In addition, the model can be used to test various hypotheses on polygene-MGE interaction.

[Truncation family selection and nonsystematic inbreeding leads to a rapid fixation of a pattern of mobile genetic elements in a computer model]. / Otsekaiushchii semeinyi otbor i bessistemnyi inbriding privodiat k bystroi fiksatsii petterna mobil'nykh geneticheskikh élementov v komp'iuternoi modeli.

A computer simulation model of the population dynamics of a polygenic system and a pattern of mobile genetic elements (MGEs) under directional truncation selection for a quantitative trait was developed. Modifier MGEs were shown to be rapidly and adaptively fixed (or lost) together with the modified polygenes. Marker MGEs and independent MGE copies were fixed and lost just as rapidly but in a random manner. Using specific marking of initial haploid genomes and direct computing of the mean proportion of identical encounters at each locus in each generation, it was shown that the mean nonselective inbreeding coefficient F(n) dramatically increases in the course of selection, reaching values 0.7-0.9 in 15-20 generations. As a result, adaptive homozygotization of polygenes and modifier MGEs and random homozygotization of marker MGEs, independent MGE copies, and all other genes of the genome occurs. These results confirm the hypothesis on the "champion" polygene pattern advanced earlier to explain the data of selection experiments.

[Distribution of motifs of functional sites in the MDG2 DNA sequence]. / Raspredelenie motivov funktsional'nykh saitov v posledovatel'nosti DNK MDG2.

Computer context analysis of the MDG2 (Dm412) DNA sequence was performed, and 530 motifs similar to functional sites from the database were identified. These motifs were found to be nonrandomly distributed along the DNA sequence. Clustering of motifs was revealed in both LTR sequences, in the regions upstream of sORF2, ORF1, and ORF2, and in the spacers between the main polypeptide domains corresponding to ORF2. The total number of clusters found is highly significant due to the presence of a group of the largest "peaks." Internal regions of some ORF contained a decreased number of site motifs (sORF1, ORF1, and ORF2.) In other words, clustering of site motifs was strongly correlated with positions of the regulatory zones in LTR and in the vicinity of the start sites of ORF and their domains. Thus, MGE of Drosophila and other organisms are considered as mobile batteries of functional sites with the increased content of half-finished motifs easily transformed into functional sites. We suggest that these sequences are involved in the adaptive rearrangements of regulatory relationships within molecular genetic regulatory systems.

[Analysis of motifs of functional MDG2 sites in assuring its possible molecular functions]. / Analiz motivov funktsional'nykh saitov MDG2 v obespechenii ego vozmozhnykh molekuliarnykh funktsii.

We analyzed the location and possible interaction of motifs of functional sites in a DNA sequence of MDG2 (Dm412) revealed by means of computer context analysis. It was shown that motifs of functional sites in the appropriate location can ensure the basic molecular functions of MDG2: expression of its ORF, transcription, induction of transposition, modification of adjacent genes and polygenes, etc. MDG2 ILTR does not contain the NTCAGTYN motif required for initiation of transcription by RNA polymerase II in the absence of the TATA box and located close to the transcription start site in most gypsy-like retrotransposons of Drosophila. Therefore, MDG2 ILTR appears to contain the classic promoter region for RNA polymerase II, contrary to other retrotransposons of the gypsy group. Enhancers of mobile genetic elements are assumed to determine modification of adjacent genes and polygenes. Excisions and transpositions of mobile elements seem to be induced by external stress factors or physiological factors through a heat-shock system.

[Population dynamics of the additive polygenic system under truncation selection]. / Populiatsionnaia dinamika additivnoi poligennoi sistemy pri otsekaiushchem otbore.

Common features of the equations describing dynamics of the additive polygenic system under truncation selection are summarized. A combination of parameters playing the role of the effective selective pressure on the ith polygenic locus was revealed. The product of mean relative fitnesses of the individual polygenic loci, [formula: see text], was shown to play the role of relative mean fitness of the polygenic population. This value depends on the measurable parameters of the character distribution in the population: [formula: see text]. It was shown that under the constant population number during truncation selection, the characteristic of the best genotype increases, [formula: see text]; which is also a product of the frequencies of preferable genotypes at individual polygenic loci. This value plays the role of the proportion of the number of the best ("champion") genotype in the population. In fact, this is the champion genotype polygene consensus pattern frequency, which a priori indicates the possibility of the champion pattern fixation. The analogue of Haldane's dilemma for the polygenic system which restrict the number of polygenes simultaneously subjected to adaptive evolution [formula: see text] was obtained for the case of constant effective population number (Ne = const).

[Analysis of the expression system of gene radius incompletes in Drosophila melanogaster]. / Analiz sistemy ékspressii gena radius incompletus u Drosophila melanogaster.

The genetic expression system of gene radius incompletes was studied by substituting regions of chromosome 3 from line th st sr ca, which has drastically reduced ri expression, to regions of chromosome 3 from a "selection" line ri s having very high expression of this gene. Virtually all chromosome 3 was shown to carry polygenes controlling phenotypic expression of oligogenic mutation ri. Chromosome regions making large (as well as small and even negative) contributions to sizes of the distal and proximal fragments of the latitudinal wing vein were found. These results suggest that the genetic system of expression does not correspond to the generally accepted postulates of K. Mather on equal, small, and additive contributions of polygenes.

[Genetic analysis of a polygenic system for a quantitative character after negative and positive selection. II. Chromosome contributions to the expression of the radial vein fragments]. / Geneticheskii analiz poligennoi sistemy kolichestvennogo priznaka posle negativnoi i pozitivnoi selektsii. II. Vklady ukromosom v 'efspessi iu fragmentov radial'noi zhilki.

Hybridological genetic analysis of a polygenic system of the character radius incompletus in Drosophila was conducted by intercrossing the contrasting selection lines riSN and riSP and crossing them with the tester line y bw st ri. Two vein segments were shown to have different polygenic systems which control penetrance and expressivity of the character. Determination of the proximal segment was additive with regard to the contribution of the haploid genomes in the hybrid zygote and to the contribution of different chromosomes. The contributions of individual chromosomes of the riSN line compared to those of the tester line were equal to -0.97 (1), -0.31 (2), and -0.14 (3). The contributions of the chromosomes of the riSP line were 0.26 (1), 0.095 (2), and 0.31 (3). Determination of the distal segment was nonadditive in all respects. Specifically, in the hybrid zygotes of riSN and the tester line, the absence of the distal segment was completely dominant over its presence; for that, only one riSN chromosome was necessary. Both intergenomic and interchromosome contributions were nonadditive. The results are discussed with regard to penetrance, expressivity and morphological mechanisms of the longitudinal wing vein formation in Drosophila.

[Mobile genetic elements and quantitative characters in Drosophila: facts and hypotheses]. / Mobil'nye geneticheskie élementy i kolichestvennye priznaki u Drozofily: fakty i gipotezy.

This review is dedicated to the comparison of the facts obtained and the proposed hypotheses, to the critical analysis of the situation arisen, and to the estimation of key propositions of the concept developed. The main point is that mobile genetic elements (MGEs) participate directly in expression, variability, selection and evolution of different quantitative characters. Genetic and selection data are considered, and hypotheses of random fixation, marker effect and direct participation of MGE patterns in expression and selection of quantitative characters are discussed. The consequences of temperature treatment are considered and hypotheses of masked selection and temperature induction of transpositions are discussed. The marker effects are shown to be non-sufficient to explain the properties of quantitative character radius incompletus system. The MGE patterns are important components of genetical system of determination of a quantitative character. MGEs modify, enhance the expression of neighbouring polygenes. Temperature effects could be explained by the influence of stress temperature treatment through the system of heat shock response on the capacity of MGEs to transcribe and transpose. The system of diversed MGE patterns in drosophila chromosomes could be believed to be universal genomic system of "soft" modification of the polygenic control of any limiting quantitative characters.

[The role of mobile genetic elements (MGE) in microevolution]. / Rol' mobil'nykh geneticheskikh élementov (MGE) v mikroévoliutsii.

The MGEs of Drosophila and other objects contain open reading frames (ORFs) encoding transposition enzymes, and "motifs" similar to functional sites: promoters, enhancers, heat shock regulatory sites, those of reception of different stress external signals and hormones, recombination sites, etc. In other words, MGE play a role of "movable cassettes of regulatory elements" in the genomes. The patterns of genome MGE localization are the important components of polygenic systems of character expression, the subjects of variation and evolution. The summed up density of MGE localization along the genome has probably the upper value corresponding to approx. 1 MGE copy per gene. The transpositional variability of MGE patterns could be random, non-random, self-related and inducible. The MGE patterns are important subjects of microevolution and reconstruction of trees of the pattern similarity is an effective method for its description. The patterns could be changed by selection of limited quantitative characters. The stress induction (temperature, treatment, dysgenic cross, etc.) stimulated the MGE transpositions and excisions, mass in population and multiple in individuals. The temperature induction acts probably through the system of response to heat shock treatment. The totality of MGE patterns make up the genomic system capable of quick reorganizations after stress external and genomic influences. The stress external influences are often correlated with passing of the population through the "bottle-neck" stage. The rate of transpositions has an upper limiting border, so named "boundary of regulation error catastrophe", that corresponds to approx. 1 transposition per genome, per generation. After the stress induction of transpositions this boundary could be exceeded, the state of the population norm becoming disrupted. The changes in MGE patterns are also supposed to accompany the changes of characters of isolation, i.e. to accompany the speciation.

[Genetic analysis of a polygenic system of a quantitative character after negative and positive selection. I. General characteristics of the polygenic system]. / Geneticheskii analiz poligennoi sistemy kolichestvennogo priznaka posle negativnoi i pozitivnoi selektsii. I. Obshchaia kharacteristika poligennoi sistemy.

Genetic analysis of phenotypic expression of the quantitative character controlled by an oligogenic mutation radius incompletus (ri) and a polygenic system in Drosophila melanogaster was carried out. Flies from the control line riC and two contrasting selection lines, riSR (positive selection) and riSN (negative selection) were crossed to the wild-type line riN. Proximal and distal segments of the longitudinal wing vein were measured in F2 ri/ri homozygotes. RiC and riN lines were shown to carry sets of polygenes with equivalent phenotypic contribution while selection lines (riSP and riSN) had an excess of polygenes of positive and negative effect, respectively. Striking similarity in some features of the polygenic system and localization of mobile genetic elements in the chromosomes of the lines was demonstrated.

[Heavy heat shock induces genetic variation in a polygenic system of a quantitative trait in Drosophila]. / Tiazhelyi teplovoi shok (TTSh) indutsiruet geneticheskuiu izmenchivost'poligennoi sistemy kolichestvennogo priznaka u Drozofily.

Results of two experiments dealing with positive and negative selection on the quantitative trait radius incompletus in an isogenic line of Drosophila melanogaster after heavy heat shock (HHS) are presented. Selection was not effective in the control without HHS. In experiment 1, in which offspring of HHS-exposed males lacked transposition induction, selection also was ineffective. By contrast, selection was highly effective in offspring of males that responded to HHS exposure by transposition induction. Thus, HHS, which is not mutagenic, generates genetic variation in a polygenic system of a quantitative trait via transpositions and excisions of mobile genetic elements. In experiment 2, positive and negative selection was conducted in three replicates, which showed concerted dynamics of the selected trait. This means that the trait dynamics is mainly related to the nearly deterministic process of accumulation of active polygenic alleles rather than to genetic drift. The induced variation of polygenic systems promotes rapid selection of "champion" genotypes. This variation is probably associated with "soft" modification of polygene expression by adjacent MGE copies.

[Effect of genotypic environment on phenotypic manifestation of radius incompletus mutation in Drosophila melanogaster]. / Vliianie geneticheskoi sredy na kharakter fenotipicheskogo proiavleniia mutatsii radius incompletus u Drosophila melanogaster.

Genetic analysis of marked regions of Drosophila chromosome 3 was performed in order to localize the "effective factors" of the polygene system that controls the expression of the limiting mutation in radius incompletus, the major-effect gene. The marked homozygous strain with genotype th st ri sr ca was crossed with the "selection" riSN strain. Contributions of the marked regions of chromosome 3 to the expression of the proximal and distal fragments of the wing radial vein were estimated. It was demonstrated that the th-st region of the marked strain contained a polygene determining a large positive contribution to the lengths of both fragments, whereas the st-ri region contained a polygene determining a large negative contribution to the length of the distal fragment compared to the riSN strain. Crossings were performed between strains that contained Mendelian mutations of the ri, ve, and vn major-effect genes of the wing vein patterns. Unexpectedly, a strong, non-additive effect of the interaction between these mutations was found. This effect was expressed as a complete disarrangement of the wing vein pattern. Each participant gene may be regarded as a large-effect polygene relative to the other genes.

[Induction of transposition and excision of mobile genetic elements in Drosophila during isogenization]. / Induktsiia transpozitsii i ékstsizii mobil'nykh geneticheskikh élementov u drozofily v protsesse izogenizatsii.

Localization patterns of mobile genetic element (MGE) Dm412 were compared in chromosomes of ten isogenic lines and a heterogeneous control line riC of Drosophila. Isogenization was shown to induce MGE transpositions and excisions. Rates of induced transpositions and excisions were, respectively, 0.35 and 0.13 per site per haploid genome per isogenization, which is significantly (by two to three orders of magnitude) higher than corresponding rates in the control line. These values are also higher by an order of magnitude than previously obtained rates of transposition induction by means of heat shock treatment and gamma-irradiation of isogenic lines. In the average haploid genome of the original line, nc = 22.14 of the occupied Dm412 sites correspond to 11.9 transpositions and 4.6 excisions generated by isogenization. Calculated for the genomic system of copia-like MGE, these rates are approximately 105 and 39 events per approximately 300 initial MGE positions. Apparently, these rates exceed the "catastrophic limit of transpositions and excisions." A hypothesis on the role of inbreeding as genomic stress in induction of transpositions and excisions was proposed. Inbreeding is assumed to increase cell concentration of defective proteins, acting via the system of heat shock response-a general system of cell response to external and physiological stresses.

[Comparative analysis of MGE 412 patterns in 18 isogenic lines of Drosophila melanogaster]. / Sravnitel'nyi analiz patternov MGE 412 v 18 izogennykh liniiakh Drosophila melanogaster.

Comparative analysis of patterns of mobile genetic element 412 was conducted in 18 isogenic lines of Drosophila melanogaster isolated in three isogenic experiments in 1987 through 1999. Twelve "extra-hot" isogenization sites (in 15-18 lines) and 23 "hot" isogenization sites (> or = 10 lines) were found; of these, 19 occurred in the original heterogeneous line. These sites virtually do not overlap with hot induction sites of transposition. Sites of the latter group generally retain their positions during isogenization. It was shown that no more than 20% of the new sites were brought from the balancer by double recombination, while inbreeding and outbreeding caused 80% of them. Different factors were shown to have different hot isogenization sites. A similarity tree was constructed for the patterns of 18 isogenic lines. The maximum peak of the tree was very low (< 0.25), i.e., the isogenic lines are more similar to than different from one another. The tree was subdivided into subtrees. The division was in good agreement with the isogenization groups corresponding to individual isogenization experiments. Significant correlation was found between the total fragment length and the number of new sites per lines.

[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].

[Expression of the quantitative trait radius incompletus in Drosophila and localization of mobile elements MDG1 and copia]. / Ekspressiia kolichestvennogo priznaka radius incompletus u drozofily i lokalizatsiia mobil'nykh élementov MDG1 i copia.

A series of subpopulations earlier obtained were studied for hybridization of mobile genetic elements (MGE). The subpopulations examined were two "selected" (ris- and ris+), two "temperature" (ri(c113) and ri(c149)) and the control (ric). The method of in situ hybridization with polytene chromosomes of larval salivary glands was used to determine the patterns of MGE localization for all subpopulations. The patterns obtained appeared to be quite different from that of mdg-2. The trees of similarity for subpopulations according to the patterns of every MGE localization were built by conventional clustering methods. These trees were topologically similar to each other and to mdg-2. Distinction spectra of patterns of four daughter subpopulations, in comparison with the control one, were shown for each of these MGE to be independent and individual. However, there are some common regularities among copia-like MGE-mdg-1, copia, mdg-2 and, probably, mdg-3, namely: non-random property of the majority of changes, the similarity of patterns for subpopulations with similar phenotypes etc. So, Drosophila genome can be conceived as a complex system of patterns of different MGE localization, capable of common or independent mass transpositions after external stress action.