[Parallelism and paradoxes on viability and the life span of two loss-of-function mutations: heat shock protein transcriptional regulator hsf(1) and l(2)gl tumor suppressor in D. melanogaster].

In this study we analyzed how a dosage decrease in mono- and diheterozygotes on both lethal alleles of the lgl-gene and hsfheat shock regulator influences viability and life span at optimal and high temperature 29 degrees C conditions. We found that hsf(1) (1 dosage of active hsf-factor) heterozygote animals had significantly increased viability (up to 30-39%) in case of its development from egg to imago under the stress of 29 degrees C. However, this stress-protective effect of a decreased dosage of HSF1 was suppressed in diheterozygotes, while the dosage of tumor suppressor lgl was simultaneously decreased. Under stress temperature conditions, a decrease in dosage of one of the alleles also increased the average life span and delayed aging, especially in the case of maternal inheritance of each of the loss-of-function mutations. In diheterozygotes the average life span had intermediate meanings. However, in diheterozygote males under stress conditions the positive longevity effect of hsf was suppressed in the presence of the lgl-mutation. Paradoxically, that decrease of expression of each of the studied vital genes provided a positive effect on both viability and life span under stress conditions. However, a simultaneous dosage decrease of two loss-of-function alleles in diheterozygotes resulted in disbalanced effects on the organism level. The received data indicate interaction between HSF1 and LGL gene products during ontogenesis and stress-defending processes.

[Effect of antioxidant responsive element inducing phenol on D. melanogaster life span].

The effect of water-soluble synthetic antioxidant TS-13 (sodium 3-(3'-tert-butyl-4'-hydroxyphenyl) propyl thiosulfonate) on life span of different lines of Drosophila melanogaster under normal conditions and survival under oxidative stress induced by hydrogen peroxide and paraquat has been investigated. Introduction to the diet of 1% TS-13 prolonged the life span of males and females of D. melanogaster long-living line Canton S, had no effect on short-living Oregon R life span and reduced the life span of male D. melanogaster line IgI(558)OR/Cy, heterozygous on tumor suppressor recessive lethal mutation. When flies were exposed to hydrogen perexide, TS-13 significantly enhanced Canton Smale and Oregon R female survival. Under the influence of paraquat antioxidant protected Canton S female and Oregon R flies of both sexes. Despite the fact that the anti-aging and protective properties of synthetic phenol antioxidant TS-13 depend essentially on the genotype and gender, in the extreme conditions of oxidative stress its positive effect pronounced.

[Variability of the exogenic antioxidant effect on survival: modeling in Drosophila lines with different lifespan and l(2)gl-tumor suppressor dosage].

Different exogenic antioxidants and geroprotectors are used to decrease age abnormalities and enhance the human life span. However, the antioxidant effect on lifespan is variable and requires detailed analysis. In the present report, we modeled in Drosophila the peculiar character of action of various doses of a new phenol antioxidant TC-13. We studied the TC-13 effect on aging of two Drosophila lines with genetically determined contrast lifespan dynamics. In addition, we tested the TC-13 antioxidant influence on the background of heterozygozity on the loss-of-function mutation of the l(2)gl tumor suppressor. The differing effect of TS-13 on LS, the character of which depends on the antioxidant dosage, genotype of line, and sex of Drosophila, was found. TS-13 in the concentration 0.2% did not affect the lifespan in all studied lines and decreased survival, whereas the antioxidant in a concentration of 1% positively affected the lifespan in both males and females of long-living lines. The antioxidant effect on animal lines with a smaller dose of tumor suppressor l(2)gl resulted in a decrease of the lifespan.

[Population genetic analysis of Drosophila melanogaster longevity: similar effects of endosymbiont Wolbachia and tumor suppressor lgl under conditions of temperature stress].

Before, it has been shown that keeping of Drosophila wild populations under temperature stress leads to prevalence of deletion alleles of tumor suppressor lgl, and higher survival of heterozygous lgl(-)/+ females descendants (haploadaptivity). On the other hand, recent investigations have demonstrated that an additional dose of lgl gene in transgenic males has inadaptive effect--cytoplasmic incompatibility, caused by the gene, is similar to the effect caused by the widespread endosymbiont Wolbachia. Both triple dose of lgl and Wolbachia infection invoke hyperexpression of some cytoskeleton proteins which leads to sperm defects and sterility of hybrid zygotes. Proceeding from this similarity, we studied the Wolbachia effect on Drosophila longevity (LG) depending on the bacteria strain, host genotype and sex, and maintenance temperature. With use of tetracycline, six Wolbachia-free lines were produced, analogical to the infected wild ones. After analyzing LG under optimal temperature conditions (25 degrees C), the lines were subdivided into three genotypic groups, differing by the LG, mortality dynamics, and type of sexual dimorphism. Under conditions of temperature stress (16 degrees C and 29 degrees C) the lines ranks with respect to LG remained as they were, though the distinctions between them were smoothed out. In other words, the effect of the genes regulating LG parameters depends on maintenance conditions. The research also revealed sharp genetic distinctions between LG parameters of two standard laboratory lines Canton and Oregon that were taken as the control. These distinctions do not disappear in crossings. In the infected lines, in seven experiments out of thirty (20% of cases) significant sex-specific influence of Wolbachia on LG was revealed, namely, in two combinations at the optimal temperature 25 degrees C, and in five combinations at stress temperatures. Under the optimal temperature conditions the endosymbiont shortened its host LG in both cases, while at stress temperatures, in four cases out of five, it extended the host LG. Females of the long-living line Bi90 (wMel) from a mountain Kirghiz population appeared to be especially sensitive to the infection carriage--their endosymbiont-caused LG extension was observed both under cold and heat stresses. This result is analogues to the effect of diminishing the oncosupressor lgl dose. In both cases LG extends only under temperature stress, and this positive effect is sex-specific.

[Genetic and epigenetic effects of lgl-tumor suppressor mutations on longevity under heat stress].

Human populations are polymorphic for risk factor mutations predisposing to diseases and cancer. The evolutionary conservative gene, tumor suppressor lethal (2) giant larvae (lgl), whose null variants are widespread in natural Drosophila populations, can be used as a model to study this phenomenon. We studied the effect of deletion and insertion mutant alleles of the lgl gene on the survival and longevity of their carriers depending on the genotype, cross direction, and action of permanent or impulse temperature stress. Under constant temperature stress, the viability and longevity of lgl/+ deletion heterozygotes increased compared to the control flies carrying two alleles of this gene. This haploid effect was maternally mediated. Exposure of deletion heterozygotes at successive oogenesis stages to moderate impulse temperature stress affected progeny survival in a similar way. The effect of impulse heating at the preembryonal stage was bidirectional: positive in the case of impulse warming of mature eggs and negative during egg differentiation. However, in both cases, deletion of one allele of the tumor suppressor gene in lgl/+ females increased survival of the next generation and delayed senescence. These data were compared to similar epigenetic transgeneration effects reported earlier for humans.

[Haploadaptivity of tumor suppressor lgl and ontogenesis in Drosophila melanogaster: increased survival rate and life span under stress conditions].

Mutations of tumor suppressor lgl induce neuroblastoma and malignant transformation of epithelial larval tissues in Drosophila. We have already shown that heterozygotes for lethal null variants lgl/+ are widespread in natural populations. In order to elucidate this paradox, we analyzed the parameters of biological adaptation of the carriers of one dose of the tumor suppressor. We studied the patterns of embryonic survival rate of lgl/+ flies under the conditions of competition for life resources and development at elevated and lowered temperatures (29 and 16 degrees C), influence of stress thermal conditions on life span, influence of short-term temperature stress during prezygotic period in the course of oogenesis of mothers on survival rate of F1 progenies, and resistance of heterozygotes for different lethal lgl alleles against RNA virus DCV. The loss of one dose of tumor suppressor lgl+ provided for increased survival rate and life span of lgl/+ heterozygotes under stress conditions. This phenomenon was called haploadaptivity. Important features of adaptogenesis were established in lgl/+ heterozygotes: dependence on the maternal genotype and critical periods in development. The increased survival rate of F1 progenies was determined already during early oogenesis of their lgl/+ mothers at the proembryo stage. With respect to humans, this conclusion draws attention to the oogenesis-dependent transgeneration aspect of determination and expression of mutant factors of risk, including tumor suppressors. The data obtained are essential for understanding of the causes of spreading null variants for the genes related to multiple pathologies, including cancer, in human populations.

[R. Goldschmidt and J. Huxley: creative parallelisms]. / R.Gol'dshmidt i Dzh. Khaksli: tvorcheskie paralleli.

The comparative analysis of scientific heritage of Richard Goldschmidt and Julian Huxley shows convincingly the resemblance of these two scientists' views over the core problems of evolutionary theory, genetics and development biology. They both contributed to developing a triad "genetics--development--evolution". The problem of a relative growth of animals was the central point in both Goldschmidt's and Huxley's works. Huxley developed a formula of the allometric growth (law of constant differential growth) while Goldschmidt was the first to draw up the broad interpretation of the consequences of that phenomenon. Both scientists belonged to initiators of development genetics and used the "non-morganian" genetics in their efforts of solving problems of macroevolution. Goldschmidt tended toward an idea of an important role of macromutation in the process of macroevolution, though Huxley adhered to more moderate views. But at the same time the concept of preadaptive mutations proposed by Huxley was close to Goldschmidt's idea of macromutants. It is shown that both scientists analyzed profoundly the changes in early stages of embryogenesis in respect to macroevolution. It is not likely to be reasonable to oppose firmly Goldschmidt's saltationism to the evolutionary synthesis of Huxley. They developed the larger biological problems in a similar way, and undoubtedly their works in the field helped to enrich the development of the views over genetics and evolution. The open-minded analysis of Goldschmidt's and Huxley's concepts leads to creating modern and up-to-date views over the theory of evolution where seemingly incompatible things go together rather well and supplement each other. Evo-Devo rediscovered Goldshmidt's Biology and Huxley's Synthesis.

["Mode for mutation" in the natural population of Drosophila melanogaster from Umani is caused by distribution of a hobo-induced inversion in the regulatory region of the yellow gene]. / "Moda na mutatsiiu" v prirodnoi populiatsii Drosophila melanogaster Umani vyzvana rasprostraneniem indutsirovannoi homo-élementom nestabil'noi inversii reguliatornoi chasti gena yellow.

A mutation outburst of the yellow gene occurred in a Drosophila melanogaster population from the town of Uman' from 1982 to 1991 and was associated with the instability of several alleles. Molecular genetic analysis revealed a deletion variant of the hobo transposable element in the same site of the regulatory region of yellow in the mutant alleles and their derivatives. The outburst of the yellow-2 mutations was attributed to the spreading of the X chromosome, which contained an inversion of the yellow regulatory region, through the population. Reinversion resulted in the wild-type phenotype. Crossing lines carrying the inversion with laboratory line C(1)DX, ywf induced instability of the yellow alleles, which was associated with duplication or multiplication of a fragment of the yellow gene. Most derivative lines eventually became stable. The loss of instability was not associated with phenotypic changes; molecular genetic changes included a loss of the duplicated sequences or a deletion of the inverted regulatory region of the yellow gene.

[Mutation bursts of the yellow gene in a natural Drosophila melanogaster population is connected with insertion of the hobo transposon]. / Vspyshki mutatsii gena yellow v prirodnoi populiatsii Drosophila melanogaster sviazany s insertsiei transpozona hobo.

In 1981, a recurrent local burst of high mutability and high allele frequency of the yellow gene was recorded in the natural population of Drosophila melanogaster from Uman', Ukraine. A detailed genetic analysis showed that hypomorphic alleles y2 prevailed during the mutation burst. Mutations were strictly allele-specific and occurred only in two directions: from y2 to y+ and from y+ to y2. Alleles y2 isolated from the natural population differed in the degree of instability of mutant and wild-type derivatives, expression of the mutant phenotype, and complementation properties. In this work, the insertion nature of all unstable alleles derived from the natural population is confirmed by direct molecular methods. The mutation burst at the yellow locus is shown to result from insertion of a defective hobo copy. Six mutations y2 independently isolated from the natural population were caused by an insertion of hobo in the same site of the yellow regulatory region. The hobo copies were identical according to the restriction map. In three y2 alleles, the mutant phenotype was associated with inversion between hobo copies, one of which was located in the yellow locus and the other, in another unidentified region of the X chromosome. The remaining y2 alleles were associated with deletions that were located in the vicinity of the hobo insertion site and in the region of yellow enhancers.

[Effect of genetic background on mutation frequency of insertional alleles of the lozenge in Drosophila melanogaster]. / Vliianie geneticheskogo fona na chastotu mutirovaniia insertsionnykh alleli gena lozenge u Drosophila melanogaster.

We studied the effect of genetic background on mutation frequency of an unstable lz75V allele of the lozenge gene (lz; 1-27.7) isolated from natural populations of Drosophila melanogaster and its mutant derivatives lzB abd lzsl. Genetic composition of the X chromosome containing unstable alleles (X75V chromosome) was shown to affect their mutability. The region of the chromosome proximal to lozenge contains factors required for high mutability of lz75V and lzB. Substitution of a distal part of the X chromosome from a laboratory strain for a homologous part of the X75V chromosome also resulted in stabilizing lz75V, but caused an increase in mutation frequency of lzB. Association between instability of lz75V and the presence of P element with the locus was revealed by in situ hybridization. Studying effects of regulatory elements from a pi 2 P strain showed that the P cytotype is associated with a twofold to threefold decrease in mutation frequency of lzB and lzsl, but P-M hybrid dysgenesis is associated with its slight increase. Regulation of instability of the lozenge gene within the X75V chromosome was assumed to involve three levels: (1) character and topography of a mobile element inserted into the locus, (2) regulatory factors of other X-chromosomal regions, and (3) cytoplasmic factors. The results obtained are discussed in terms of regulation of transposition of mobile genetic elements.

[Genetic instability in the Drosophila melanogaster lozenge locus: characteristics of the lz75V locus]. / Geneticheskaia nestabil'nost' v lokuse lozenge u Drosophila melanogaster: kharakteristika allelia lz75V.

Genetic properties of lz75V, an unstable allele of the lozenge locus, are described. The lz75V allele appeared in progeny of a male from a Far East natural population of Drosophila melanogaster. Mutation of this allele produces a broad spectrum of mutant derivatives with phenotypes varying from normal to extreme. The arising alleles can be stable or unstable. Some lz75V derivatives continuously preserve their spontaneous mutability in laboratory conditions, whereas other alleles of the same family show progressive stabilization at the intralocus or intrachromosome level. Instability of the lz75V-bearing X chromosome is locus-specific: only the lozenge gene mutates with high frequency, while visible mutations at other loci rarely occur. As shown previously, the lz75V allele appears to be caused by a P-element insertion. The appearance of spontaneous instability is discussed with regard to the general problem of transposition regulation in mobile elements. Different systems of hybrid dysgenesis, and, in particular, P elements are assumed to play an important role in induction of unstable mutations in nature.

[MR-chromosomes in Eurasian populations of Drosophila melanogaster]. / MR-khromosomy v evraziiskikh populiatsiiakh Drosophila melanogaster.

In natural populations of Drosophila melanogaster, two mutator systems, MR and P-M, are distributed throughout the world. Some evidence shows that these systems can be considered as one. Natural populations of D. melanogaster from Eurasia and North America are fundamentally different with regard to the P-M system. Comparison of Eurasian and North American populations with regard to the MR system was hindered by a lack of data concerning distribution and frequency of MR factors in Eurasia. In this paper, data on the MR-active chromosomes in natural populations of D. melanogaster from Russia and neighboring countries from 1977 to 1992 are presented. The frequencies of MR chromosomes in Eurasian populations were shown to be similar to those in North America. Hence, on a global scale, the MR and P-M mutator systems are expressed independently.

[Preparation and primary genetic analysis of Drosophila melanogaster transformants line w'lz(b)/XXywf, containing mini-white genes, integrated in the genome during P-element-dependent transformation]. / Poluchenie i pervichnyi geneticheskii analiz transformantov Drosophila melanogaster linii w'lz(b)/XXywf, soderzhashchikh gen mini-white, integrirovannyi v genom pri P-élementzavisimoi transformatsii.

Transformation of Drosophila melanogaster using P-element-based vectors yielded 129 sublines, which carried mini-white gene copies in the different genome regions. Dependence of mini-white gene expression on the location, gene dosage, and sex of the transformed individuals was analyzed. The mutation lzb was shown to suppress mini-white gene expression, the degree of suppression depending on the location and dosage of the mini-white gene.

[Current state of the genetics of the white locus in Drosophila melanogaster]. / Sovremennaia genetika lokusa white u Drosophila melanogaster.

The modern data on structure, transcription of the white locus of Drosophila melanogaster and its insertional alleles, including unstable ones, are considered. Special attention is paid to the transvection effect (synapsis-dependent interaction between white and zeste genes), cis-acting regulatory elements and the behaviour of the white genes introduced into the genome by P element-mediated DNA transformation.

[Interaction of mobile elements P and mdg3 in Drosophila melanogaster: genetic aspects]. / Vzaimootnoshenie mobil'nykh élementov P i mdg3 u Drosophila melanogaster: geneticheskii aspekt.

It was found earlier that two unstable sn mutants isolated from natural populations are connected with insertion of mobile element mdg3 into the 7D1-2 region where singed gene (1-21.0) is localised. From two original sn mutants, a series of unstable sn alleles, both mutant and normal for phenotype, was extracted. Then we studied, how they change the mutation rate in germinal and somatic cells of different hybrids with pi 2 stock having P cytotype and active P elements in the chromosomes. Addition of P chromosomes, independently of the background of cytoplasm, proved to reduce the sn instability. The level of sn mutability was decreased with increasing the dose of P chromosomes. It is suggested that mutation events are caused by transposition of mdg3 and that both mdg3 and P elements compete for the same cellular factor, capable of activation of transposition process.

[Pedigree in which multiple pregnancy is combined with sterility]. / Rodoslovnaia, v kotoroi mnogoplodie sochetaetsia s besplodiem.

A case of simultaneous hereditary transmission of twinning and sterility in a jewish family from Novosibirsk is described. The both characters are transmitted by male and female. It is suggested that twinning and sterility are connected with the action of one dominant mutation with multiple pleiotropic action on propagation system. The action of two alleles in homozygotes is additive. The importance of special search for and study of similar situations for understanding mechanisms of twinning and sterility occurrence in man is discussed.

[Possible cytogenetic mechanisms of direct paternal influence on the human twinning tendency and their consequences: a hypothesis]. / Vozmozhnye tsitogeneticheskie mekhanizmy priamogo ottsovskogo vliianiia na bliznetsovost' u cheloveka i ikh sledstviia: gipoteza.

Certain cytogenetic mechanisms are suggested to explain the puzzling cases of the direct male influence on the repeated twin births in mammals including humans. The hypothesis is based on the peculiarities of female oogenesis and meiosis, the peculiarities of fertilization and on the established facts of the occurrence of true viable chimaeras produced by separate fertilization of two meiotic products of oogenesis. We postulate that definite genetic factors are transferred from the paternal side whose products become active in male gametes and promote penetration of two spermatozoa (polyspermy) or appearance of two male pronuclei in the egg cytoplasm. The results of such events may be twinning and occurrence of chimaeric or heteroploid individuals. The appearance of viable twins produced by male-dependent polyspermy may be considered as a fortunate outcome of various possible cytogenetic anomalies of fertilization, meiosis, and cleavage divisions. The existence of non-canonical cases of twins, except mono-and dizygotic ones is postulated, according to the hypothesis. Twins pairs produced by two paternal and one maternal genomes may be called "one and halfzygotic or sesquizygotic". The different types of twins may be classified in an order, according to the degree of genetic similarity; monozygotic, chimaeric, sesquizygotic chimaeric, sesquizygotic and dizygotic. This gives an opportunity to explain the appearance of 2 to 3% of "doubtful cases" in mass classification of twin pairs into mono- and dizygotic. The verification of the hypothesis involves the special thorough genetic and cytogenetic analysis of all twin sibs and their parents in families with the direct paternal influence on twin births.(ABSTRACT TRUNCATED AT 250 WORDS)