[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.

[Modeling dynamics of gene net, regulating the cell cycle in mammalian cells]. / Modelirovanie dinamiki gennykh setei, reguliruiushchikh kletochnyi tsikl v kletakh mlekopitaiushchikh.

The study of the molecular mechanisms determining cellular programs of proliferation, differentiation, and apoptosis is currently attracting much attention. Recent studies have demonstrated that the system of cell-cycle control based on the transcriptional regulation of the expression of specific genes is responsible for the transition between programs. These groups of functionally connected genes from so-called gene networks characterized by numerous feedbacks and a complex behavioral dynamics. Computer simulation methods have been applied to studying the dynamics of gene networks regulating the cell cycle of vertebrates. The data on the regulation of the key genes obtained from the CYCLE-TRRD database have been used as a basis to construct gene networks of different degrees of complexity controlling the G1/S transition, one of the most important stages of the cell cycle. The behavior dynamics of the model constructed has been analyzed. Two qualitatively different functional modes of the system has been obtained. It has also been shown that the transition between these modes depends on the duration of the proliferation signal. It has also been demonstrated that the additional feedback from factor E2F to genes c-fos and c-jun, which was predicted earlier based on the computer analysis of promoters, plays an important role in the transition of the cell to the S phase.

[Induction of MGE 412 transposition in an isogenic strain of Drosophila melanogaster by different doses of ethanol fumes]. / Induktsiia transpozitsii MGE 412 razlichnymi dozami parov étanola v izogennoi linii Drosophila melanogaster.

The effect of treatment of males from an isogenic Drosophila melanogaster strain by limiting doses of ethanol fumes on transpositions of MGE 412 was examined. Validity of the phenomenon of transposition induction was demonstrated. We estimated rates of induced transposition (approximately 10(-2) events per site, per sperm, per generation versus < 10(-3) in control) and showed dose dependence of the rate on the exposure time of the males to ethanol fumes. Experiments with alcohol treatment at limiting doses must end either in death of the individuals or bursts of genetic variability in their progeny. In terms of genetics of an individual, this may mean loss of vital hereditary basis followed by mass degradation of the progeny of the "hard drinkers." In terms of populations genetics, this mode of MGE transposition induction can rapidly create a burst of novel genetic variation, which, apart of great losses, may generate a number of advantageous individuals, i.e., be significant for population survival in new, stressful environments.

[Negative selection and computer models of the joint evolution of the patterns of polygenes, transposable elements, and origin identity labels]. / Negativnyi otbor v komp'iuternoi modeli sovmestnoi évoliutsii patternov poligenov, MGE i MIP.

Computer simulation of the population dynamics of the genomic patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of negative selection for an additive quantitative trait has been performed. It was demonstrated that active polygene alleles disappear very rapidly, whereas the patterns of TEs and OILs continue their evolution determined by strict selective inbreeding and gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. It was demonstrated that the final consensus pattern of OILs consists of the fragments of the original patterns, which contain neither active polygene alleles nor modifier or marker TEs. Neutral TE copies were present in the final pattern, as should be expected in the case of gene drift. Inbreeding coefficient increased steadily but by generation 100 reached values higher than 0.9. All other parameters and initial conditions being the same, the responses to negative and positive selections were asymmetric.

[Stabilizing selection and computer models of the joint evolution of patterns of polygenes, transposable elements, and origin identity labels]. / Stabiliziruiushchii otbor v komp'iuternoi modeli sovmestnoi évoliutsii patternov poligenov, MGE i MIP.

A computer model of the populations dynamics of the patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of stabilizing selection for an additive quantitative trait (with the target value being 0.4 of the maximum) was analyzed. It was demonstrated that the final plateaus of the trait value and the frequencies of the active values of polygenes are reached rapidly, namely, within five to seven generations (the effective selection period). The inbreeding coefficient during this period also grows rapidly and then gradually increases eventually reaching approximately 0.7. The inbreeding coefficient reaches plateau (at approximately 1.0) only in generations 300-350, which suggests the effect of gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. By generation 100 of selection, the final patterns of TEs and OILs were not formed completely. Fixations and losses, especially those of the OIL pattern, were delayed. In general, however, the population heterogeneity with respect to the patterns studied does not stabilize. This heterogeneity decreases the case of stabilizing selection, although more slowly than in the cases of positive and negative selections.

[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.

[Induction of MGE 412 transposition individually by heat and cold shock in spermatogenesis in Drosophila males]. / Induktsiia transpozitsii MGE 412 razdel'no teplovym i kholodovym shokom v spermatogeneze u samtsov drozofily.

Effects of temperature treatment (heavy heat shock, HHS; heat shock, HS; and cold shock, CS) on the daily productivity of treated males in different spermatogenesis stages have been studied in isogenic line 51 of Drosophila melanogaster. The average productivity was shown to substantially decrease in all cases. The sum of the HS and CS contributions to this decrease was nearly equal to the HHS (the combined HS and CS) contribution, i.e., these contributions were almost additive. The temperature treatments did not kill mature sperm. In the control, mating productivity of day 1 exceeded that of the next day at least by 10-20%. Each day, most sperm in matings was new, i.e., matured during that day. Transposition induction of MGE 412 was studied at four spermatogenesis stages after HS and CS. Both temperature treatments were effective but CS had a more pronounced inducing effect. Most temperature-induced transpositions occurred at stage 3 (meiosis) and 4 (spermiogenesis). The day rates of transpositions at different stages were estimated. After HS at the meiosis stage, lambda = 0.11 events per initial MGE copy per sperm per day of mating, which is approximately equal to the previous estimates after HHS. After CS at the meiosis stage, lambda = 0.51. The transposition hot sites (including the previously known 43B and 97DE as well as a number of new sites) were detected. The lists of transpositions after CS completely included the corresponding lists after HS, which suggests similarity of induction mechanisms underlying CS and HS.

[Prolongation of MGE 412 transposition induction after gamma-irradiation in an isogenic line of Drosophila melanogaster]]. / Prolongatsiia induktsii transpozitsii MGE 412 posle gamma-oblucheniia v izogennoi linii Drosophila melanogaster.

The dose dependence of the rate of gamma-induced transpositions and consequent dynamics of the MGE 412 pattern after gamma-irradiation were investigated in isogenic line 49 in generations F1, F12, F140, and F170. It was shown that the results on dose dependence of transpositions was very similar with the corresponding results of the classic works by Timofeeff-Ressovsky et al. (1935). It is suggested that the transcribed copies of retrotransposon 412 "cure" gamma-radiation-induced double-strand DNA breaks. The phenomenon of prolongation of MGE transposition induction during early generations after treatment was shown. In this period (F1-F12), the maximum transposition rate (lambda approximately equal to 2 x 10(-2) events per MGE copy, per haploid genome, per generation) and the maximum number of heterozygous MGE copies were achieved. In the late generations (F140 and F170), the reduced induction level (lambda approximately 10(-3) was established. In the population of effective size Ne = 2000 individuals, this corresponds to the state when lambda >> 1/4Ne, i.e., when the transposition flow prevails over the MGE copy loss by genetic drift. These data together with some indirect evidence argue for the hypothesis that the spontaneous transposition rate is proportional to the average number of heterozygous MGE copies per diploid genome.

[Computer modeling of joint selection response of MGE patterns and a polygenic system]. / Komp'iuternoe modelirovanie sobmestnogo otklika na otbor patternov MGE i poligennoi sistemy.

Using computer simulation, selection response of three genome patterns--polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)--were studied. In each generation of selection, variability of each pattern type was described by on UPGMA tree. Stringent positive truncation selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95-96% and 70-80% of respectively enforced and non-enforced active polygenic alleles were fixed (2-3% and 16-17% lost). In all generations, Hkn < or = Dkn of the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85-88% (lost for 11-12%); marker MGEs, for 60-70 (lost for 21-25%); and independent copies, for 30-40 (lost for 50-60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16:3 for modifier MGEs, 15:6 for marker MGEs, and 25:28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random.

[Response of the MGE 412 pattern to truncation selection of a quantitative trait in an isogenic line of drosophila after severe heat shock (SHS)]. / Otklik patterna MGE 412 na otsekaiushchii otbor kolichestvennogo priznaka v izogennoi linii drozofil posle tiazhelogo teplovogo shoka (TTSh).

Positive and negative selection on the total length of two fragments of an interrupted longitudinal wing vein in an isogenic line of Drosophila melanogaster was accompanied by changes in the genomic localization pattern of MGE 412. Strong truncation selection was conducted in the population of effective size Ne = 160 for 50 generations. Twenty-six out of 35 polymorphic HHS-induced segments of MGE localization behaved as independent copies and markers, whereas 9 segments proved to be selective. The second group included "hot" segments of HHS transposition induction (43B, 97E, etc.). Thus, final consensus patterns of induced MGE transpositions have a random and an adaptive component in generation 50 of positive and negative selection. Selective patterns probably include modifier MGEs, which generate induced genetic regulatory variation of polygenes controlling the selected quantitative trait in the isogenic line after HHS.

[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.

[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.

[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.

Heavy heat shock induced retrotransposon transposition in Drosophila.

The phenomenon of transposition induction by heavy heat shock (HHS) was studied. Males of a Drosophila isogenic line with a mutation in the major gene radius incompletus (ri) were treated by HHS (37 degrees C for 1 h followed by 4 degrees C for 1 h, with the cycle repeated three times) and crossed to untreated females of the same line. The males were crossed 5 d after heat shock, and also 9 d after HHS. Many transpositions were seen in the F1 larvae by in situ hybridization. The rate of induced transposition was at least 2 orders of magnitude greater than that of the control sample, and was estimated to be 0.11 events per transposable element copy per sperm. Two 'hot' subdivisions for transpositions, induced probably during the post-meiotic stage of spermiogenesis, were found: 43B and 97DE. Three-quarters of all transpositions were localized in these positions. In other sites the rates of induced transpositions were (1.3-3.2) x 10(-2) events per occupied segment per sperm, 1 order of magnitude greater than those of the control.

[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).

[Comparison of the synonymous and non-synonymous substitution rates in various regions of the neuraminidase and hemagglutinin genes of the influenza A virus]. / Sravnenie skorosti nakopleniia sinonimicheskikh i nesinonimicheskikh zamen dlia razlichnykh raionov genov neiraminidazy i gemaggliutinina virusa grippa A.

A new, statistically justified approach was used to estimate the synonymous and non-synonymous substitution rates in several antigenic variants of influenza-virus surface proteins. The rates were compared for antigenic and nonantigenic regions of neuraminidase and hemagglutinin, as well as for neuraminidase surface and internal amino acids identified by X-ray analysis. For neuraminidase, the estimation was performed for the first time. The non-synonymous substitution rate was shown to be significantly higher in antigenic than in nonantigenic sites. However, neither subsample of antigenic sites displayed a fixation rate of non-synonymous substitutions higher than that of synonymous substitutions, which would confirm the effect of positive selection on these sites and argue against a neutral evolution character. Specific features of methods used to estimate the substitution fixation rates and problems in their interpretation are discussed.

[Different patterns of molecular evolution of influenza A viruses in avian and human population]. / Razlichie rezhimov molekuliarnoi évoliutsii virusov grippa A v populiatsiiakh ptits i cheloveka.

Patterns of molecular evolution of the influenza virus proteins and genes are discussed. The subsets of all viral genes corresponding to statistically significant clusters on dendrogram were shown to fall into two distinct groups. The first group was characterized by the presence of an exact linear relationship between the year of the strain isolation and the evolutionary distance. The subsets of human influenza virus genes belong to this group. A method for eliminating the "frozen" strains from the subsets and for calculating the evolutionary rates without construction of phylogenetic trees has been elaborated. The substitution rates calculated according to this technique agreed with the data obtained previously. A linear relationship was not observed in the second group. This group was predominantly composed of avian influenza virus genes. The lack of linear correlation pointed to the cocirculation of a large amount of different influenza virus genomic segments in the avian population. An approach for an examination of the role of intragenic recombination in the development of the antigenic subtypes of hemagglutinin is suggested. Our results suggest that recombination did not play a considerable role in this process, and that all modern subtypes of this protein were probably formed before the introduction of the influenza viruses into the human population. These findings are consistent with the hypothesis that influenza viruses penetrated into human population from their pools in avian populations.

[Population dynamics of the response of the genomic pattern of the mobile genetic element Dm412 in Drosophila on selection for a quantitative trait]. / Populiatsionnaia dinamika otklika genomnogo patterna MGE Dm412 drozofily na otbor po kolichestvennomu priznaku.

In an isogenic line of Drosophila melanogaster carrying the Mendelian mutation radius incompletus, selection for the total length of two segments of the disrupted longitudinal wing vein was conducted. After gamma-irradiation at a dose of 13 Gy, positive and negative truncation selection became highly effective and was completed in 50 generations. The pattern of mobile genetic element Dm412 was almost completely fixed in the course of selection. In the positive direction of selection, fixations of mobile genetic element (MGE) sites exceeded losses; in the negative direction, this relationship was reversed. The number of MGE sites in the pattern increased from 23 to 33 and to 26 in the positive and negative directions, respectively. The mean heterozygosity of MGE sites decreased respectively ten and six times. The dynamics of some sites (6F, 43B, 66A, 69E, and others) corresponded to that expected with an adaptive response to selection. Two out of these sites (43B and 66A) were previously assigned to hot sites of Dm412 transposition induced by heat shock. Fixation and loss of sites continued on average for tens of generations. Four hypotheses describe the relationship between patterns of polygenes and MGE in the context of explanation of the above facts: (1) genetic drift; (2) the linkage of MGE and polygenes without modification of the latter (hitchhiking); (3) the linkage and modifying effect of MGE on polygenes linked with them; (4) the selection of the "champion" pattern of polygenes and a random or adaptive MGE pattern linked with it. Hypotheses 1 and 2 are unlikely, hypothesis 3 is possible in the case of other selection modes, whereas hypothesis 4 seems to be most plausible.