Interaction of the p53 DNA-binding domain with its n-terminal extension modulates the stability of the p53 tetramer

The tetrameric tumor suppressor p53 plays a pivotal role in the control of the cell cycle and provides a paradigm for an emerging class of oligomeric, multidomain proteins with structured and intrinsically disordered regions. Many of its biophysical and functional properties have been extrapolated from truncated variants, yet the exact structural and functional role of certain segments of the protein is unclear. We found from NMR and X-ray crystallography that the DNA-binding domain (DBD) of human p53, usually defined as residues 94-292, extends beyond these domain boundaries. Trp91, in the hinge region between the disordered proline-rich N-terminal domain and the DBD, folds back onto the latter and has a cation-π interaction with Arg174. These additional interactions increase the melting temperature of the DBD by up to 2 °C and inhibit aggregation of the p53 tetramer. They also modulate the dissociation of the p53 tetramer. The absence of the Trp91/Arg174 packing presumably allows nonnative DBD-DBD interactions that both nucleate aggregation and stabilize the interface. These data have important implications for studies of multidomain proteins in general, highlighting the fact that weak ordered-disordered domain interactions can modulate the properties of proteins of complex structure.     

Natural selection causing microsatellite divergence in wild emmer wheat at the ecologically variable microsite at Ammiad, Israel

Genetic diversity at 28 microsatellite loci was studied in a natural population of Triticum dicoccoides at the Ammiad microsite, north of the Sea of Galilee, Israel. This microsite was subdivided into four major habitats, North, Valley, Ridge and Karst, and further subdivided into nine subhabitats. The units thus defined showed strong and highly significant differentiation in ecological factors; in particular with respect to cover, proximity and height of rocks, and surface soil moisture after early rains. The results showed that allele distributions at microsatellite loci were nonrandom and associated with habitats. Significant genetic differentiation and variation in repeat number were found among subpopulations in the four major habitats and nine subhabitats. Habitat-specific and -unique alleles and linkage disequilibria were observed in the Karst subpopulation. The subpopulations dwelling in drier habitats and subhabitats showed higher genetic diversities at microsatellite loci. These results suggest that natural selection, presumably through aridity stress, acts upon microsatellite divergence predominantly on noncoding sequences, thereby contributing to differences in fitness. Received: 9 September 1999 / Accepted: 16 September 1999     

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.     

Effect of aging on the cardiovascular regulatory systems in healthy women

Aging, independently from the hormonal status, is a major risk factor for cardiovascular morbidity in healthy women. Therefore, we studied the effect of healthy aging on the cardiovascular homeostatic mechanisms in premenopausal and postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal women, confirmed by follicular-stimulating hormone (FSH) and luteal hormone (LH) levels, were compared with 14 normally menstruating women during the early follicular phase (young-EF), to avoid as much as possible the effects of estrogen. Systolic BP was 108 +/- 1.5 vs. 123 +/- 2.5 (P < 0.001), supine norepinephrine was 260 +/- 30 vs. 216 +/- 45 and upright 640 +/- 100 vs. 395 +/- 50 pg/ml (P = 0.05) in young-EF vs. postmenopausal, respectively. Plasma renin activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased significantly with aging (young-EF vs. postmenopausal): high-frequency (HF) band, root mean square successive differences (rMSSD) and proportion of R-R intervals >50 ms (PNN50%) were 620 +/- 140 vs. 270 +/- 70 (P = 0.04), 53 +/- 7 vs. 30 +/- 3 (P = 0.02), and 23 +/- 5 vs. 10 +/- 3 (P = 0.04), respectively. LF to HF ratio was 0.85 +/- 0.17 in young-EF and became 1.5 +/- 0.22 in postmenopausal (P = 0.03). Both arms of the baroreflex, +BRS (29 +/- 5 vs. 13.5 +/- 2.5, P = 0.01) and -BRS (26 +/- 4 vs. 15 +/- 1.5, P = 0.02) decreased with aging. Cardiovascular alpha(1)-adrenoreceptor responsiveness significantly increased and beta-decreased in postmenopausal compared with young EF (P < 0.001, both). The corrected QT intervals (QTc) were similar, whereas corrected JT intervals (JTc) and JTc to QTc ratio were prolonged in the postmenopausal group. We conclude that in young women, parasympathetic control is the main regulator of the cardiovascular system and in postmenopausal women, sympathetic tone dominates. The transition from parasympathetic to sympathetic control may contribute to the increased cardiovascular morbidity with aging.     

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. dicoccoides and for the tagging of agronomically important traits derived from wild emmer wheat. Received: 27 February 2001 / Accepted: 22 March 2001     

Morphometrics of speciating mole rats: Adaptive differentiation in ecological speciation

The morphometrics of subterranean mole rats, Spalax ehrenbergi superspecies in Israel, were studied. A total of 42 skull and body variables of 327 adults from 44 populations across the ranges of the 4 chromosomal species (2n = 52, 54, 58 and 60) were measured. The results showed: a. in general, significantly higher morphological values in males than in females; b. significant interspecific quantitative diffferences in 15 skull variables of males, and in 3 of females; but no qualitative diagnosis of any of the species; c. an intercorrelation between most skull variables at different orgamsmal levels, and a uniform and complete correlation with weight; d. a statistical discrimination in both metric and nonmetric multivariate analyses between most species pairs; e. an indication of high morphological similarity based on the relatively small multivariate Mahalanobis distances of dissimilarity between species; f. a possible explanation for a significant part of the variance in most skull and body variables resulting from a combination of temperature variables and water availability; g. a declination in size in skull and body variables between northern and southern species; h. the order of speciation events to be 2n = (54, 52)→58→60. Based on these results we conclude: 1. no morphological breaks are associated with the speciation of the S. ehrenbergi complex, and morphological differentiation is quantitative rather than qualitative between the species: 2. morphological diversity is significantly explained by climatic selection, and is therefore adaptive and explicable on even very low selective pressures over evolutionary time: 3. the morphospecies seem unable to reliably reflect the biological species in the S. ehrenbergi complex, and morphological differentiation, at least in this superspecies, evolves in a gradual rather than a punctual way: this would conform with Neo-Darwinian evolutionary theory.     

Brain size diversity in adaptation and speciation of subterranean mole rats

We have tested brain size diversity and encephalization in the actively speciating subterranean mole rats of the Spalax ehrenbergi superspecies in Israel. Our sample involved 171 individuals comprising 12 populations and 4 chromosomal species (2n = 52, 54, 58 and 60) distributed parapatrically from the northern Mediterranean region southward (2n = 52, 54→+58→60) into increasingly more arid and unpredictable climatic regimes, approaching the Negev Desert. Our results indicate that relative brain size and encephalization are highest in 2n = 60 as compared with 2n = 52, 54 and 58. We hypothesize that this pattern is adaptive and molded by natural selection. Brain evolution and higher encephalization in the S. ehrenbergi complex appears to be associated with increasing ecological stresses of aridity and climatic unpredictability.     

The Ecology and Evolution of Fruit Odor: Implications for Primate Seed Dispersal

Primates are now known to possess a keen sense of smell that serves them in various contexts, including feeding. Many primate species are frugivorous and provide essential seed dispersal services to a variety of plants. Studies of pollination ecology, and recently seed dispersal ecology, indicate that animal mutualist behavior exerts selection pressures that drive changes in flower and fruit traits. As a result, the use of olfaction in in primate feeding ecology may have affected the evolution of fruit odor in species that rely on primate seed dispersal. However, this hypothesis is seldom tested. Here, we summarize the available information on how primates may have affected the evolution of fruit odor. We ask what the chemistry of primate fruit odor may look like, what information fruit odor may convey, whether there are geographical differences in fruit odor, and what other factors may affect the odor of fruits consumed by primates. We identify many gaps in the available data and offer research questions, hypotheses, and predictions for future studies. Finally, to facilitate standardization in the field, we discuss methodological issues in the process of odor sampling and analysis.