Genetic effects on microsatellite diversity in wild emmer wheat (Triticum dicoccoides) at the Yehudiyya microsite, Israel.

This study investigated allele size constraints and clustering, and genetic effects on microsatellite (simple sequence repeat, SSR) diversity at 28 loci comprising seven types of tandem repeated dinucleotide motifs in a natural population of wild emmer wheat, Triticum dicoccoides, from a shade vs sun microsite in Yehudiyya, northeast of the Sea of Galilee, Israel. It was found that allele distribution at SSR loci is clustered and constrained with lower or higher boundary. This may imply that SSR have functional significance and natural constraints. Genetic factors, involving genome, chromosome, motif, and locus significantly affected SSR diversity. Genome B appeared to have a larger average repeat number (ARN), but lower variance in repeat number (sigma(ARN)(2)), and smaller number of alleles per locus than genome A. SSRs with compound motifs showed larger ARN than those with perfect motifs. The effects of replication slippage and recombinational effects (eg, unequal crossing over) on SSR diversity varied with SSR motifs. Ecological stresses (sun vs shade) may affect mutational mechanisms, influencing the level of SSR diversity by both processes.

Climatic effects on microsatellite diversity in wild emmer wheat (Triticum dicoccoides) at the Yehudiyya microsite, Israel.

Microsatellite (SSR) diversity at 28 loci comprising seven types of tandem dinucleotide repeated motifs was analyzed in 105 individual plants of wild emmer wheat, Triticum dicoccoides, from a microsite in Yehudiyya, northeast of the Sea of Galilee, Israel. The study area was less than 1000 m(2) and involved 12 paired plots distributed in a mosaic pattern. Each experiment involved very close (a few meters apart), but sharply divergent, microclimatic niches in the open park forest of Tabor oak: (1) sun, between trees, and (2) shade, under tree canopy. Significant microclimatic divergence characterized many loci displaying asymmetric and non-random distribution of repeat numbers. Niche-specific and niche-unique alleles and linkage disequilibria were found in the two sub-populations. Microsatellite diversity at both single- and two-locus levels is affected by microclimatic environment. The evidence reflects effects of ecological stresses and natural selection on SSR diversity, resulting presumably in adaptive structures.

Microsatellite polymorphism in natural populations of wild emmer wheat, Triticum dicoccoides, in Israel.

Diversity in 20 microsatellite loci of wild emmer wheat, Triticum dicoccoides, was examined in 15 populations (135 genotypes) representing a wide range of ecological conditions of soil, temperature, and water availability, in Israel and Turkey. An extensive amount of diversity at microsatellite loci was observed despite the predominantly selfing nature of this plant species. The 20 Gatersleben wheat microsatellites (GWM), representing 13 chromosomes of genomes A and B of wheat, revealed a total of 364 alleles, with an average of 18 alleles per GWM marker (range: 5-26). The proportion of polymorphic loci per population averaged 0.90 (range: 0.45- 1.00); genic diversity, He, averaged 0.50 (range 0.094- 0.736); and Shannon's information index averaged 0.84 (range 0.166-1.307). The coefficients of genetic distance between populations were high and averaged D=1.862 (range 0.876-3.320), an indication of sharp genetic divergence over short distances. Interpopulation genetic distances showed no association with geographic distance between the population sites of origin, which ruled out a simple isolation by distance model. Genetic dissimilarity values between genotypes were used to produce a dendrogram of the relationships among wild wheat populations by the unweighted pair-group method with arithmetic averages (UPGMA). The results showed that all the wild emmer wheat populations could be distinguished. Microsatellite analysis was found to be highly effective in distinguishing genotypes of T. dicoccoides, originating from diverse ecogeographical sites in Israel and Turkey, with 88% of the 135 genotypes correctly classified into sites of origin by discriminant analysis. Our present microsatellite results are non-random and in agreement with the previously obtained allozyme and RAPD patterns, although the genetic-diversity values obtained with microsatellites are much higher. Significant correlates of microsatellite markers with various climatic and soil factors suggest that, as in allozymes and RAPDs, natural selection causes adaptive microsatellite ecogeographical differentiation, not only in coding, but most importantly in non-coding genomic regions. Hence, the concept of "junk DNA" needs to be replaced by at least partly regulatory DNA. The obtained results suggest that microsatellite markers are useful for the estimation of genetic diversity in natural populations of T. dicoccoidesand for the tagging of agronomically important traits derived from wild emmer wheat.

Protein folding: looping from hydrophobic nuclei.

Protein structure can be viewed as a compact linear array of nearly standard size closed loops of 25-30 amino acid residues (Berezovsky et al., FEBS Letters 2000; 466: 283-286) irrespective of details of secondary structure. The end-to-end contacts in the loops are likely to be hydrophobic, which is a testable hypothesis. This notion could be verified by direct comparison of the loop maps with Kyte and Doolittle hydropathicity plots. This analysis reveals that most of the ends of the loops are hydrophobic, indeed. The same conclusion is reached on the basis of positional autocorrelation analysis of protein sequences of 23 fully sequenced bacterial genomes. Hydrophobic residues valine, alanine, glycine, leucine, and isoleucine appear preferentially at the 25-30 residues distance one from another. These observations open a new perspective in the understanding of protein structure and folding: a consecutive looping of the polypeptide chain with the loops ending primarily at hydrophobic nuclei.

Distinct stages of protein evolution as suggested by protein sequence analysis.

Evolution of proteins encoded in nucleotide sequences began with the advent of the triplet code. The chronological order of the appearance of amino acids on the evolution scene and the steps in the evolution of the triplet code have been recently reconstructed (Trifonov, 2000b) on the basis of 40 different ranking criteria and hypotheses. According to the consensus chronology, the pair of complementary GGC and GCC codons for the amino acids alanine and glycine appeared first. Other codons appeared as complementary pairs as well, which divided their respective amino acids into two alphabets, encoded by triplets with either central purines or central pyrimidines: G, D, S, E, N, R, K, Q, C, H, Y, and W (Glycine alphabet G) and A, V, P, S, L, T, I, F, and M (Alanine alphabet A). It is speculated that the earliest polypeptide chains were very short, presumably of uniform length, belonging to two alphabet types encoded in the two complementary strands of the earliest mRNA duplexes. After the fusion of the minigenes, a mosaic of the alphabets would form. Traces of the predicted mosaic structure have been, indeed, detected in the protein sequences of complete prokaryotic genomes in the form of weak oscillations with the period 12 residues in the form of alteration of two types of 6 residue long units. The next stage of protein evolution corresponded to the closure of the chains in the loops of the size 25-30 residues (Berezovsky et al., 2000). Autocorrelation analysis of proteins of 23 complete archaebacterial and eubacterial genomes revealed that the preferred distances between valine, alanine, glycine, leucine, and isoleucine along the sequences are in the same range of 25-30 residues, indicating that the loops are primarily closed by hydrophobic interactions between the ends of the loops. The loop closure stage is followed by the formation of typical folds of 100-200 amino acids, via end-to-end fusion of the genes encoding the loop-size chains. This size was apparently dictated by the optimal ring closure for DNA. In both cases the closure into the ring (loop) rendered evolutionarily advantageous stability to the respective structures. Further gene fusions lead to the formation of modern multidomain proteins. Recombinational gene splicing is likely to have appeared after the DNA circularization stage.

Very high mutation rate in offspring of Chernobyl accident liquidators.

Exposure to ionizing radiation has long been suspected to increase mutation load in humans. Nevertheless, such events as atomic bombing seem not to have yielded significant genetic defects. The Chernobyl accident created a different, long-term exposure to radiation. Clean-up teams (or 'liquidators') of the Chernobyl reactor are among those who received the highest doses, presumably in some combination of acute and chronic forms. In this study, children born to liquidator families (currently either in the Ukraine or Israel) conceived after (CA) parental exposure to radiation were screened for the appearance of new fragments using multi-site DNA fingerprinting. Their sibs conceived before (CB) exposure served as critical internal controls, in addition to external controls (non-exposed families). An unexpectedly high (sevenfold) increase in the number of new bands in CA individuals compared with the level seen in controls was recorded. A strong tendency for the number of new bands to decrease with elapsed time between exposure and offspring conception was established for the Ukrainian families. These results indicate that low doses of radiation can induce multiple changes in human germline DNA.

Abundant multilocus polymorphisms caused by genetic interaction between species on trait-for-trait basis.

This paper deals with the problem of polymorphism maintenance in species coevolution mediated by selection for quantitative traits controlled by Mendelian genes. We showed here that the conditions for polymorphism maintenance in interacting species can be deduced from the behavior of the isolated partners in stable and changing environments. This allows also to address such difficult questions as evolution of sex and recombination, that can not be considered properly in non-Mendelian models. An abundance of polymorphic regimes was revealed in the proposed genetic model. The obtained results demonstrate a remarkable property of trait-dependent coevolution concerning the conditions for maintenance of genetic polymorphism: what seems to be more realistic, that is, non-equal gene effects and deviation from purely additive within-locus gene action, promotes polymorphism.

Complex limiting behaviour of multilocus genetic systems in cyclical environments.

Here we demonstrate that complex limiting behaviour (supercycles and chaotic-like phenomena) may arise in a rather broad and natural class of multilocus systems, both haploid and diploid, experiencing stabilizing selection with cyclically varying optima over a short period. These include loci with purely additive, dominant, or semidominant effects, with different types of their chromosome distribution. The observed complex dynamics appeared to manifest a certain stability with respect to disturbances of parameters specifying the structure of the selected system and environmental characteristics. This mode of multilocus dynamics by far exceeds the potential attainable under ordinary selection models resulting in simple behaviour. It may represent a novel evolutionary mechanism increasing genetic diversity over long time periods. This novel mechanism could contribute to the observation that biological diversity has increased over geological time regardless of the well-known massive extinctions.

Sequential estimation of linkage between PCR-generated markers and a target gene employing stepwise bulked analysis.

PCR-based markers are used for targeting plant genes. However, mapping these markers requires laborious and expensive analysis of individual genotypes. We propose here a sequential procedure for fine mapping of PCR markers relative to a target gene. Stepwise bulked analysis is employed to get a censored estimation of the recombination rate. The sequential estimation is compared to fixed sample size design. In both cases, the proposed procedure can achieve a substantial reduction in the number of PCR runs (up to 90-97% for close linkage) as compared to the standard individual-by-individual analysis.

Linkage between quantitative trait loci and marker loci: resolution power of three statistical approaches in single marker analysis.

This paper presents a comparison of three methods of parameter estimation in analysis of linkage between a quantitative trait locus (QTL) and a marker locus: maximum likelihood, mean square for trait cumulative distribution function, and method of moments, employing simulated backcross data. The sensitivity of estimates to violation of assumptions of normality and equal variances were also studied. Some measures of discrepancy between the trait distributions in the QTL groups are considered to evaluate the potential dependence of the resolution capacity of the QTL substitution effect with respect to trait mean value and variance.

Complex dynamics of multilocus systems subjected to cyclical selection.

Earlier we have shown that oscillations with a long period ("supercycles") may arise in two-locus systems experiencing cyclical selection with a short period. However, this mode of complex limiting behavior appeared to be possible for narrow ranges of parameters. Here we demonstrate that a multilocus system subjected to stabilizing selection with cyclically moving optimum can generate ubiquitous complex limiting behavior including supercycles, T-cycles, and chaotic-like phenomena. This mode of multilocus dynamics far exceeds the potential attainable under ordinary selection models resulting in simple behavior. It may represent a novel evolutionary mechanism increasing genetic diversity over long-term time periods.

Genetic supercycles caused by cyclical selection.

Typical behavior of a two-locus genetic system experiencing cyclical selection, includes fixation (in one or both loci) or a stable polymorphic cycle with a period equal to that of environmental changes. By considering the time scale in terms of environmental periods, the last case could be trivially classified as a polymorphic stable point. Here we report on some results showing the complex limiting behavior of diploid population trajectories resulting from selection in a cyclically changing environment. We found that simple cyclical selection could produce genetic supercycles composed of many hundreds of environmental periods.

Interval mapping of quantitative trait loci employing correlated trait complexes.

An approach to increase the resolution power of interval mapping of quantitative trait (QT) loci is proposed, based on analysis of correlated trait complexes. For a given set of QTs, the broad sense heritability attributed to a QT locus (QTL) (say, A/a) is an increasing function of the number of traits. Thus, for some traits x and y, H(xy)2(A/a) > or = H(x)2(A/a). The last inequality holds even if y does not depend on A/a at all, but x and y are correlated within the groups AA, Aa and aa due to nongenetic factors and segregation of genes from other chromosomes. A simple relationship connects H2 (both in single trait and two-trait analysis) with the expected LOD value, ELOD = -1/2N log(1-H2). Thus, situations could exist that from the inequality H(xy)2(A/a) > or = H(x)2(A/a) a higher resolution is provided by the two-trait analysis as compared to the single-trait analysis, in spite of the increased number of parameters. Employing LOD-score procedure to simulated backcross data, we showed that the resolution power of the QTL mapping model can be elevated if correlation between QTs is taken into account. The method allows us to test numerous biologically important hypotheses concerning manifold effects of genomic segments on the defined trait complex (means, variances and correlations).

Linkage between loci of quantitative traits and marker loci: multi-trait analysis with a single marker.

An efficient approach to increase the resolution power of linkage analysis between a quantitative trait locus (QTL) and a marker is described in this paper. It is based on a counting of the correlations between the QTs of interest. Such correlations may be caused by the segregation of other genes, environmental effects and physiological limitations. Let a QT locus A/a affect two correlated traits, x and y. Then, within the framework of mixture models, the accuracy of the parameter estimates may be seriously increased, if bivariate densities f aa(x, y), f Aa(x, y) and f AA(x, y) rather than the marginals are considered as the basis for mixture decomposition. The efficiency of the proposed method was demonstrated employing Monte-Carlo simulations. Several types of progeny were considered, including backcross, F2 and recombinant inbred lines. It was shown that provided the correlation between the traits involved was high enough, a good resolution to the problem is possible even if the QTL groups are strongly overlapping for their marginal densities.

Cyclical behavior of genotype frequencies in a two-locus population under fluctuating haploid selection.

Numerical iterations have shown that periodic haploid two-locus selection with nonoverlapping generations can produce large-scale cyclical behavior with a period differing significantly from the environmental period. Among other types, we observed slowly damping oscillations with very long periods, stable T-cycles with a length containing several environmental periods, and chaotic-like dynamics. Possible biological implications are discussed.

[Adaptive bioregulation in the treatment of essential hypertension with cerebrovascular disorders]. / Adaptivnoe bioregulirovanie v lechenii bol'nykh gipertonicheskoi bolezn'iu s tserebrovaskuliarnymi narusheniiami.

The authors developed a system of adaptive bioregulation based on the principle of biological feedback. Sixty hypertensive patients with the initial forms of cerebrovascular disturbances and 30 clinically healthy subjects were examined. Adaptive bioregulation is successfully realized in the technical system with a visual control of changes in the REG area. The treatment is associated with normalization of the tonus, vessel blood filling, arterial pressure and clinical status of patients. Adaptive bioregulation may be one of the methods of treatment of patients with cerebrovascular pathology. The effect of its use is determined by the duration and nature of the disease.

[Bioelectric and vegetative reactions of the rat to stimulation of the ventromedial hypothalamus]. / Bioélektricheskie i vegetativnye reaktsii u krys pri stimuliatsii ventromedial'nogo gipotalamusa.

Neurophysiological and correlational analysis was carried out to investigate the influence of stimulation of negative zones in the ventromedial hypothalamus on dynamics of electroencephalographic and vegetative parameters. The stimulation used led to an appearance of theta-rhythm initially in the stimulated structure, followed by an increase of plasticity of the system of bioelectrogenesis and regulation of vegetative functions. Stimulation of the negative zones of the ventromedial hypothalamus led to a formation of pathological excitation focus mainly at the limbic level with special cyclic type of cortico-subcortical relations. Increase of rigidity of the systems of electrogenesis and regulation of vegetative functions was accompanied by a formation of closed reverberatory cycle of integrations of the hypothalamus, hippocampus, and neocortex and by a change in autocorrelational functions reflecting an increase of general synchroneity .