Biomedical subjects

V A Ratner

Publications and source records attributed to V A Ratner.

At least 37 records · Page 2Linked to original sources

PubMed1998

[Different patterns of molecular evolution of influenza A viruses in avian and human population].

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.

Animals↗

PubMed1998

[Population dynamics of the response of the genomic pattern of the mobile genetic element Dm412 in Drosophila on selection for a quantitative trait].

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.

Animals↗

PubMed1998

[Comparison of the synonymous and non-synonymous substitution rates in various regions of the neuraminidase and hemagglutinin genes of the influenza A virus].

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.

Amino Acid Substitution↗

PubMed1998

[New evidence for the induction of mobile genetic element transpositions by severe heat shock].

The induction of retrotransposon 412 transpositions by stress was studied in detail. Males of an isogenic line carrying the radius incompletus (ri) mutation of the Mendelian gene were exposed to heavy heat shock (HHS). The procedure consisted of treatment at 37 degrees C for 1 h and at 4 degrees C for 1 h, with reciprocal changes of developmental temperature 3 times, sequentially; the males were then crossed with untreated females. The same males were crossed both on the fifth and ninth day after the HHS treatment. On the basis of in situ hybridization in 85 F1 larvae, 193 transpositions were identified. After treatment, the transposition rate increased by two orders of magnitude (compared to control) and amounted to 0.11 events per site of the original isogenic line per spermium per generation. Two hot sites (segments) of preferential transposition localization, 43B and 97CD, were detected after the first cross; these sites comprised more than 3/4 of all transpositions. Sperm from the first cross were exposed to HHS during the time period of 120 to 244 h after the appearance of the corresponding germline cells, probably at the stage of spermatid maturation. The overinduction of transpositions was shown to occur in these sites and at this stage. In the remaining sites, after the first cross, and in all sites, after the second cross, the rate of induced transpositions was (1.3-3.1) x 10(-2) events per site per spermium per generation, which is higher than in the control by an order of magnitude. This basic induction level was observed at all stages of spermatogenesis. The induction of transposition by heavy heat shock may be considered established.

Animals↗

PubMed1997

[Stress induction of retrotransposon transposition in Drosophila: reality of the phenomenon, characteristic features, possible role in rapid evolution].

A polygenic system of expression of the quantitative character radius incompletus was shown to be sensitive to external and physiological stresses: heat shock, gamma-irradiation, isogenization, etc. This stress response involved mobilization of retrotransposons. Heavy heat shock induced transpositions of Dm412 and B104 in three and one isogenic lines, respectively. The induced transposition rate was (2.5-11.0) x 10(-2) per site per sperm per generation, i.e., 1-2 orders of magnitude higher than for spontaneous transpositions. Induction of transpositions by gamma-radiation yielded similar estimates. Recently, induction of transpositions and excisions by isogenization was demonstrated; transposition and excision rates were, respectively, 0.35 and 0.13 per site per sperm per generation, which was 2-3 orders of magnitude higher than in control lines. In all these cases, stress induction of retrotransposon transpositions was mediated by molecular mechanisms of the heat shock system-the general system of cell resistance to external and physiological stress factors. From the viewpoint of evolution, stress induction of transpositions is a powerful factor generating new genetic variation in populations under stressful environmental conditions. Passing through a "bottleneck," a population can rapidly and significantly alter its population norm and become the founder of new, normal forms.

Animals↗

PubMed1996

[Evolution modes of eukaryote retrotransposons].

A number of general problems of molecular macroevolution of retroposons were examined, including the question of the ratio of the contributions of genomic replication and retrotransposition to mutational variability of retrotransposons, as well as that of the influence of stress-induced transpositional variability on the rate of evolution and the phylogenetic trees of retrotransposons. It is thought that the substitution fixation rate in genes of retrotransposons is determined by the transposition rate and the probability of mutation upon replication of copies of retransposons in the genome and upon retrotransposition, as well as by selection stabilizing the function of proteins of the retroreplicative mechanism. By means of molecular-evolutionary parameters, estimated for Drosophila retrotransposons and animal retroviruses, it was shown that spontaneous retrotransposition makes the dominant contribution to the frequency of mutation, and the expected fixation rate of nucleotide substations is on the order of 2 x 10(-8) per position per year. This version of evolution of retrotransposons agrees with the results of phylogenetic analysis of trees of macroevolution. Another version, associated with stress-induced transpositions, gives a very high rate of evolution, on the order 3 x 10(-6) fixations of nucleotide substitutions per position per year. This version seems improbable, as it leads to a significant hidden genetic load.

Animals↗

PubMed1996

[Distribution of motifs of functional sites in the MDG2 DNA sequence].

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.

Animals↗

PubMed1996

[Analysis of motifs of functional MDG2 sites in assuring its possible molecular functions].

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.

Enhancer Elements, Genetic↗

PubMed1996

[Induction of transposition and excision of mobile genetic elements in Drosophila during isogenization].

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.

Animals↗

PubMed1995

[Comparative analysis of patterns of localization of mobile genetic elements in genetic selection experiments on Drosophila melanogaster].

A comparative selection-genetic analysis of three heterogeneous lines of Drosophila melanogaster with an interrupted longitudinal wing vein was performed. In the control line, riC, and two selection lines, riSP and riSN, overall patterns of localization of six families mobile genetic elements (MGE) (MGE) (MDG1, MDG2, MDG3, MDG4, copia, and 297) were compared. In all, the lines contained 220 sites (copies) in 153 segments of the Bridges' map. According to response to selection, six classes of sites were identified: strong positive (P), weak positive (p), neutral (n), weak negative (n), strong negative (N), and abnormal (A). More than 50% of the sites (P+N+p+n) were shown to respond to selection; the contrasting classes (P and N and p and n) counterbalanced each other. These sites are assumed to mark actual parts of the genome, where polygenes are located. In other words, more than 50% of the total number of the genome sites act as polygenes controlling this quantitative character and respond to selection. Pleiotropy of polygenes in such a system must be very high. 22.2% of sites are neutral (class 0); apparently, they do not mark polygenes. The remaining 21.8% of sites (class A) show an anomalous response to selection. They are assumed to mark the polygenes of another genetic system, which participated in the maintenance of homeostasis in the original line riC. On the basis of this evidence, the concept of oligogenes and polygenes is developed. Oligogenes and polygenes are genes that occupy respectively limiting and nonlimiting positions in systems of expression. Adaptive properties of oligogenes are evaluated first and evolve rapidly. Adaptive properties of polygenes are evaluated only with regard to their total set and are limited by oligogenes. Variation of polygenic systems is generated by polygenic combination and spontaneous transpositions and excisions of MGE.

Animals↗

PubMed1995

[Analysis of changes in MGE localization of Drosophila after selection and temperature treatment using Southern blot-hydridization].

For five heterogeneous lines of Drosophila melanogaster (riC, riSN, riSP, riT113, and riT149), patterns of DNA restriction fragments, containing different mobile genetic elements (MGE), were obtained by means of Southern blot hybridization. Using densitometry of gel radioautographs, differences between patterns were estimated and distance matrices and similarity dendrograms constructed. Judging by these dendrograms, lines riSN (selected in negative direction) and riT113 (treated with temperature) are most similar both for patterns of MGEs Dm412, I-3', and jockey; and for the expression of the quantitative character radius incompletus. The similarity in MGE patterns was shown to be determined mainly by more similar spectra of acquisition and loss of bands (fragments), than in the control line (riC). Earlier, the same results were obtained for MGEs Dm412, MDG1, and copia, using in situ hybridization. It is assumed that during selection, a consensus pattern of the selected line is largely formed by transpositions and excisions of MGE, which either modify the expression of adjacent polygenes or mark adjacent polygenes with large effect. Under temperature stress, non-random induced transpositions and excisions generate hot sites and site haplotypes. If they affect polygene expression, they also fall into consensus patterns of contrasting "temperature" lines and form correlation between the character expression and MGE localization pattern.

Animals↗

PubMed1995

[Induction of transposition of MGE Dm412 using gamma-irradiation of an isogenic line of Drosophila melanogaster].

In an isogenic line of Drosophila, transpositions of mobile genetic elements (MGE) Dm412 were induced by gamma-radiation at doses of 300, 800, and 1300 R. The rates of induced transpositions were (for each dose, respectively) 3.9 x 10(-3), 1.0 x 10(-2), and 1.87 x 10(-2) events per occupied site per haploid genome of the isogenic line per generation. Thus, the transposition rate increased linearly with the radiation dose. The specific rate of gamma-radiation-induced transpositions was (1.3 +/- 0.6) x 10(-5) per occupied site per haploid genome of the isogenic line per Roentgen per generation. gamma-radiation-induced hot transposition sites and haplotypes, very similar to those induced by heat shock, were found. It was suggested that the mechanism of temperature induction than to the direct mutational effect of gamma-radiation. Estimates of induced transposition rates per genome for each dose were calculated as 1.1, 3.0, and 5.6 events, respectively, per genome per generation. This level probably corresponds to the subthreshold level of genomes near the "catastrophic border of transpositional losses."

Animals↗

PubMed1995

[Evolution of gypsy-group retrotransposons: phylogenetic analysis of domains included in the pol-polyprotein].

Transposons of gypsy group are assigned to LTR-containing retrotransposons present in the genomes of invertebrates, fungi, and plants. In this work, a theoretical analysis of the potential products of ORFs of these retrotranposons was conducted. Alignments were obtained and trees of similarity were constructed for domains of the POL region. On the basis of the obtained data, two hypothetically monophyletic subgroups of transposons were distinguished within the framework of the gypsy group, settling the genomes of taxonomically related organisms (the subgroup of "true" gypsy of insects and the subgroup of gypsy-like transposons of plants and fungi). A number of peculiarities of the topology of these trees hypothetically indicate cases of genetic conversion and recombination of domains accompanying the evolution of this group. The amino acid substitution fixation rate was evaluated on the basis of comparison of sequences of the protein products of ORFs. Estimates of the time of divergence of subgroups of gypsy-group transposons are significantly less than estimates of the times of divergence of their host species. One explanation for this discrepancy might be the hypothesis of settlement by transposons of the genomes of isolated host species.

Amino Acid Sequence↗

PubMed1994

[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].

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.

Animals↗

PubMed1994

[Effect of heat shock on transpositions of Mobile Genetic Element Dm412 in three isogenetic lines of Drosophila melanogaster].

Induction of Dm412 transpositions by heavy heat shock was studied in several isogenic lines of Drosophila melanogaster. The probabilities of spontaneous and induced transpositions were estimated. Their respective values were less than < 3.0 x 10(-3) and 3.8 x 10(-2) per site per genome per generation in line 51, and less than < 3.6 x 10(-3) and 2.6 x 10(-2) in line 66. These estimates are close to those obtained earlier for Dm412 (less than < 3.3 x 10(-4) and 7.2 x 10(-2) and for B104, line 49 (less than < 1.7 x 10(-3) and 8.1 x 10(-2)). Thus, transposition induction of copia-like mobile genetic elements by heavy heat shock is a general phenomenon common for various isogenic lines of Drosophila. Other properties of Dm412 and B104 transpositions, such as the presence of "hot" and "cold" sites, HSI haplotypes etc., are also similar.

Animals↗

PubMed1994

[Multiple induction of transpositions of Mobile Genetic Element B104 in Drosophila with severe heat shock].

Induction of transpositions by heavy heat shock (HHS) was demonstrated for the copia-like mobile genetic element B104. The probability of transposition induction lambda HHS was equal to 8.1 x 10(-2) per site per spermatozoon per spermatozoon per generation, which is an order of magnitude higher than the upper limit of spontaneous transposition probability estimate, lambda k < 1.7 x 10(-3). "Hot" and "cold" transposition sites were found. Many multisite heat shock haplotypes were shown to be nonrandom combinations of independent single-site transpositions. Multiples of numerous heat shock haplotypes exceeded expected values, which suggest-s that they were selected either in male germline cells or at the level of gametic fertility. These data confirm our earlier results obtained for Dm412. Heat shock transposition induction can be considered as a general property of different copia-like mobile genetic elements in Drosophila.

Animals↗

PubMed1994

[Genetic analysis of a polygenic system of a quantitative character after negative and positive selection. I. General characteristics of the polygenic system].

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.

Animals↗

PubMed1993

[The genetic language: grammar, semantics, evolution].

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.

Codon↗