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Enhancement of telomere-plasmid segregation by the X-telomere associated sequence in Saccharomyces cerevisiae involves SIR2, SIR3, SIR4 and ABF1.

We have previously shown that circular replicating plasmids that carry yeast telomere repeat sequence (TG1-3) tracts segregate efficiently relative to analogous plasmids lacking the TG1-3 tract and this efficient segregation is dependent upon RAP1. While a long TG1-3 tract is sufficient to improve plasmid segregation, the segregation efficiency of telomere plasmids (TEL-plasmids) is enhanced when the X-Telomere Associated Sequence (X-TAS) is also included on the plasmids. We now demonstrate that the enhancement of TEL-plasmid segregation by the X-TAS depends on SIR2, SIR3, SIR4 and ABF1 in trans and requires the Abf1p-binding site within the X-TAS. Mutation of the Abf1p-binding site within the X-TAS results in TEL-plasmids that are no longer affected by mutations in SIR2, SIR3 or SIR4, despite the fact that other Abf1p-binding sites are present on the plasmid. Mutation of the ARS consensus sequence within the X-TAS converts the X-TAS from an enhancer element to a negative element that interferes with TEL-plasmid segregation in a SIR-dependent manner. Thus, telomere associated sequences interact with TG1-3 tracts on the plasmid, suggesting that the TASs have an active role in modulating telomere function.

Base Sequence↗

Mitochondrial genotype segregation in a mouse heteroplasmic lineage produced by embryonic karyoplast transplantation.

Mitochondrial genotypes have been shown to segregate both rapidly and slowly when transmitted to consecutive generations in mammals. Our objective was to develop an animal model to analyze the patterns of mammalian mitochondrial DNA (mtDNA) segregation and transmission in an intraspecific heteroplasmic maternal lineage to investigate the mechanisms controlling these phenomena. Heteroplasmic progeny were obtained from reconstructed blastocysts derived by transplantation of pronuclearstage karyoplasts to enucleated zygotes with different mtDNA. Although the reconstructed zygotes contained on average 19% mtDNA of karyoplast origin, most progeny contained fewer mtDNA of karyoplast origin and produced exclusively homoplasmic first generation progeny. However, one founder heteroplasmic adult female had elevated tissue heteroplasmy levels, varying from 6% (lung) to 69% (heart), indicating that stringent replicative segregation had occurred during mitotic divisions. First generation progeny from the above female were all heteroplasmic, indicating that, despite a meiotic segregation, they were derived from heteroplasmic founder oocytes. Some second and third generation progeny contained exclusively New Zealand Black/BINJ mtDNA, suggesting but not confirming, an origin from an homoplasmic oocyte. Moreover, several third to fifth generation individuals maintained mtDNA from both mouse strains, indicating a slow or persistent segregation pattern characterized by diminished tissue and litter variability beyond second generation progeny. Therefore, although some initial lineages appear to segregate rapidly to homoplasmy, within two generations other lineages transmit stable amounts of both mtDNA molecules, supporting a mechanism where mitochondria of different origin may fuse, leading to persistent intraorganellar heteroplasmy.

Animals↗

Fixation, segregation and linkage of allozyme loci in inbred families of the Pacific oyster Crassostrea gigas (Thunberg): implications for the causes of inbreeding depression.

The effect that inbreeding has on the fixation and segregation of genes has rarely been confirmed by direct observation. Here, fixation, segregation, and linkage of allozymes is investigated in the progeny of self-fertilized hermaphrodites of the normally outcrossing Pacific oyster Crassostrea gigas. The estimate of fixation pooled over loci, individuals, and families, F = 0.462, is significantly lower than the expected value of 0.5. Log-likelihood ratios reveal significant heterogeneity in fixation among individuals, among families, and among loci. In addition, the grand pooled segregation ratio, 127:243:54, deviates significantly from 1:2:1, with a bias against homozygotes for alleles of lesser frequency in the natural population. Segregation ratios for 11 of 14 loci are significantly heterogeneous among families, and exact tests for segregation within families reveal 16 significant results out of 51 tests. Thus, fixation and segregation of allozyme markers in inbred oyster families deviates from the expectations of neutral inbreeding theory. Di-genic disequilibria are significant for four of 74 di-locus pairs revealing two linkage groups. Strong viability selection is apparently conditional on the genotype of the hermaphrodite-founders and is largely focused on these two linkage groups. These genetic effects are explained by interaction between cis-linked factors and polymorphic regulatory backgrounds.

Animals↗

Molecular mapping of segregation distortion loci in Aegilops tauschii.

Distorted segregation ratios of genetic markers are often observed in progeny of inter- and intraspecific hybrids and may result from competition among gametes or from abortion of the gamete or zygote. In this study, 194 markers mapped in an Aegilops tauschii F2 population were surveyed for distorted segregation ratios. Region(s) with skewed segregation ratios were detected on chromosomes 1D, 3D, 4D, and 7D. These distorter loci are designated as QSd.ksu-1D, QSd. ksu-3D, QSd.ksu-4D, and QSd.ksu-7D. Three regions of segregation distortion identified on chromosome 5D were analyzed in two sets of reciprocal backcross populations to analyze the effect of sex and cytoplasm on segregation distortion. Extreme distortion of marker segregation ratios was observed in populations in which the F1 was used as the male parent, and ratios were skewed in favor of TA1691 alleles. There was some evidence of differential transmission caused by nucleo-cytoplasmic interactions. Our results agree with other studies stating that loci affecting gametophyte competition in male gametes are located on 5DL. The distorter loci on 5DL are designated as QSd.ksu-5D.1, QSd.ksu-5D.2, and QSd.ksu-5D.3.

Chromosome Mapping↗

The genetic architecture necessary for transgressive segregation is common in both natural and domesticated populations.

Segregating hybrids often exhibit phenotypes that are extreme or novel relative to the parental lines. This phenomenon is referred to as transgressive segregation, and it provides a mechanism by which hybridization might contribute to adaptive evolution. Genetic studies indicate that transgressive segregation typically results from recombination between parental taxa that possess quantitative trait loci (QTLs) with antagonistic effects (i.e. QTLs with effects that are in the opposite direction to parental differences for those traits). To assess whether this genetic architecture is common, we tabulated the direction of allelic effects for 3252 QTLs from 749 traits and 96 studies. Most traits (63.6%) had at least one antagonistic QTL, indicating that the genetic substrate for transgressive segregation is common. Plants had significantly more antagonistic QTLs than animals, which agrees with previous reports that transgressive segregation is more common in plants than in animals. Likewise, antagonistic QTLs were more frequent in intra- than in interspecific crosses and in morphological than in physiological traits. These results indicate that transgressive segregation provides a general mechanism for the production of extreme phenotypes at both above and below the species level and testify to the possible creative part of hybridization in adaptive evolution and speciation.

Adaptation, Physiological↗

Genetic instability of sporulation-associated characters in a Bacillus subtilis mutant: analysis of the segregation pattern and genetic studies.

A Bacillus subtilis mutant which formed dark-brown 'medusa' (M) colonies was obtained. It sporulated at a high frequency, overproduced extracellular protease during sporulation and possessed a high genetic instability with a complex segregation pattern. Segregation was maintained after repeated re-isolation of single M colonies. The major wild-type-like class of segregants (B) was stable, sporulated normally and produced normal amounts of protease. Occasionally segregants were obtained which produced extremely high amounts of protease, sporulated poorly, formed transparent colonies and were either highly unstable (TD) or stable (TDst). Rarely B(D) (stable, normal sporulation and protease overproduction) and W and T (both stable and asporogenous) segregants were produced. The M phenotype was transmitted as a single factor by transformation but not by transduction. The results of transduction experiments suggest the presence of two mutations, ScoC and ScoD. It is proposed that this new segregating system in B. subtilis may result from tandem duplication of part of the bacterial chromosome.

Alleles↗

Angle of repose and segregation in cohesive granular matter.

We study the effect of fluids on the angle of repose and the segregation of granular matter poured into a silo. The experiments are conducted in two regimes where: (i) the volume fraction of the fluid (liquid) is small and it forms liquid bridges between particles thus giving rise to cohesive forces, and (ii) the particles are completely immersed in the fluid. The data is obtained by imaging the pile formed inside a quasi-two-dimensional silo through the transparent glass side walls and using color-coded particles. In the first series of experiments, the angle of repose is observed to increase sharply with the volume fraction of the fluid and then saturates at a value that depends on the size of the particles. We systematically study the effect of viscosity by using water-glycerol mixtures to vary it over at least three orders of magnitude while keeping the surface tension almost constant. Besides surface tension, the viscosity of the fluid is observed to have an effect on the angle of repose and the extent of segregation. In case of bidisperse particles, segregation is observed to decrease and finally saturate depending on the size ratio of the particles and the viscosity of the fluid. The sharp initial change and the subsequent saturation in the extent of segregation and angle of repose occurs over similar volume fraction of the fluid. Preferential clumping of small particles causes layering to occur when the size of the clumps of small particles exceeds the size of large particles. We calculate the azimuthal correlation function of particle density inside the pile to characterize the extent of layering. In the second series of experiments, particles are poured into a container filled with a fluid. Although the angle of repose is observed to be unchanged, segregation is observed to decrease with an increase in the viscosity of the fluid. The viscosity at which segregation decreases to zero depends on the size ratio of the particles.

Journal Article↗

Primitive stream segregation of tone sequences without differences in fundamental frequency or passband.

Peripheral-channeling theorists argue that differences in excitation pattern between successive sounds are necessary for stream segregation to occur. The component phases of complex tones comprising unresolved harmonics (F0=100 Hz) were manipulated to change pitch and timbre without changing the power spectrum. In experiment 1, listeners compared two alternating sequences of tones, A and B. One sequence was isochronous (tone duration=60 ms, intertone interval=40 ms). The other began isochronously, but the progressive delay of tone B made the rhythm irregular. Subjects had to identify the sequence with irregular rhythm. Stream segregation makes this task more difficult. A and B could differ in passband (1250-2500 Hz, 1768-3536 Hz, 2500-5000 Hz), component phase (cosine, alternating, random), or both. Stimuli were presented at 70 dB SPL in pink noise. Dissimilarity in either passband or phase increased discrimination thresholds. Moreover, phase differences raised threshold even when there was no passband difference. In experiment 2, listeners judged moment-by-moment the grouping of long ABA-ABA-... sequences. The measure was the proportion of time a sequence was heard as segregated. The factors that increased segregation were very similar to those that increased threshold in experiment 1. Overall, the findings indicate that substantial stream segregation can occur without differences in power spectrum. It is concluded that differences in peripheral channeling are not a requirement for stream segregation.

Adult↗

The influence of different timbre attributes on the perceptual segregation of complex-tone sequences.

Spectral factors such as differences in harmonic content are powerful cues in the perceptual organization of tone sequences. Temporal features such as rise time, however, have been shown to be poor cues [W. M. Hartmann and D. Johnson, Mus. Perc. 9, 155-184 (1991)]. The relative influence of these timbral features on perceptual segregation was investigated. Complex tones were sequenced in a repeating ABA- "gallop" format, under four conditions in which tones A and B had the same or different timbres as defined by differences in numbers of harmonics and temporal-envelope features. A sequence started with A and B tones at the same F0. The F0 difference between A and B then increased over the course of a trial, until a listener terminated the trial indicating perceptual segregation into sub-sequences comprising A and B tones, respectively. The F0 difference required to reach this crossover point of segregation provided a measure of the efficacy of stimulus features of A and B as cues for perceptual organization. Sequences combining differences in harmonic structure and temporal envelope required the smallest F0 change for segregation. Sequences of tones with the same harmonic structure and temporal envelope required larger changes in F0, while the other conditions fell in the middle of this range. The F0-tracking method used in this study facilitates measurement of the relative contribution of different stimulus features to stream segregation. It also holds potential as a tool using the point of segregation as a measure of the magnitude of timbre differences brought about by different physical features of sounds.

Adult↗

Inequality, residential segregation by income, and mortality in US cities.

STUDY OBJECTIVE: This study was designed to discover whether the relation between income inequality and population death rates within the United States was mediated by the degree of residential segregation between rich and poor. DESIGN: Using data for 276 metropolitan areas in the USA, residential segregation was defined as the extent to which people with different levels of income live in the same or different census tracts. Two segregation measures were used: the ratio of income inequality between household within tracts to the inequality in average income between tracts, and the Jargowsky Neighbourhood Sorting Index. MAIN RESULTS: Results suggest that segregation within urban areas is associated with an additional mortality burden. However, the association between income inequality and mortality in these metropolitan statistical areas was found to be independent of the degree of economic segregation between their constituent neighbourhoods. CONCLUSIONS: Most of the association between income inequality and mortality is not mediated by the effects of greater residential segregation.

Adolescent↗

Linkage and segregation distortion in Drosophila melanogaster.

Segregation distortion is caused by a group of genetic elements in and near the centric heterochromatin of chromosome 2 of Drosophila melanogaster. These elements promote their preferential recovery in heterozygous males by rendering sperm bearing the homologous chromosome dysfunctional. Previous work has shown that numerous Y-autosome translocations are associated with the suppression of the segregation distorter phenotype. The present study examined the effects of translocations between the major autosomes upon the expression of segregation distortion. Autosomal translocations involving either the segregation distorter chromosome or its sensitive homologue had no significant effect upon the expression of segregation distortion. These results argue that linkage arrangement per se may not have a major effect on segregation distortion. The suppression of SD by specific Y-autosomal translocations may be due to the disruption of elements on the Y chromosome that are important for the expression of SD.

Analysis of Variance↗

Segregation analysis of the mouse Rb(6.16) translocation in zygotes produced by heterozygous female carriers.

The segregation products in zygotes of females heterozygous for the mouse Rb(6.16) translocation were studied. Of 191 first-cleavage metaphase zygotes recovered from 16 females mated to chromosomally normal males, 132 were cytogenetically analyzed after sequential G- and C-banding. There were no products of adjacent segregation, since the six chromosomal imbalances were unrelated to the translocation. Alternate segregation was seen in 126 (95.5%) of the zygotes, with 85 being chromosomally normal and 41 carrying the translocation. These results indicate preferential alternate segregation and a significant deviation from the Mendelian 1:1 ratio (P < 0.005) for reciprocal alternate segregants, as seen earlier for males with this translocation. However, the approximately 2:1 ratio for normal-to-balanced segregants in females is lower than the ratios consistently seen for males. This supports the notion that there are different underlying causes of the distortion in the sexes.

Animals↗

The racial segregation of hospital care revisited: Medicare discharge patterns and their implications.

OBJECTIVES: This paper measures current patterns of hospital segregation among Medicare beneficiaries. METHODS: Data from the fiscal year 1993 Medicare Provider Analysis and Review (MEDPAR) file, the index of dissimilarity, and a linear regression model are used to test the effects of standard metropolitan area characteristics on hospital segregation. RESULTS: The overall hospital segregation index was 0.529, ranging by state from 0.154 to 0.746. Hospital segregation in 126 standard metropolitan areas was positively related to population size, hospital density, and residential segregation and negatively related to income inequities and location in the South. CONCLUSIONS: Racial segregation remains high and may produce both reporting biases and unequal effects of public policy.

Black or African American↗

[Ooplasmic segregation and morphological axis formation in the polychaete Nereis virens embryo].

Ooplasmic segregation is of great importance in the development of Annelida. The mechanisms of this process are very diverse in different groups of polychaetes, oligochaetes, and leeches (Fernandez et al., 1998). Ooplasmic segregation in Nereis virens is connected with the first meiotic spindle formation and animal-vegetative axis appearance. Spherical polyaxial symmetry of the oocyte transforms into radial stratified symmetry in the course of ooplasmic segregation. There are two main steps of ooplasmic segregation in Nereis virens. The first step begins after the cortical reaction when the central clear cytoplasm reaches the surface of the oocyte. The movement of the cytoplasm is sensitive to nocodazole, colchicine, and cytochalasin B and appears to be mediated by microtubules and, partly, by microfilaments. The second step is not sensitive to the microtubule inhibitors and is mediated mainly by actin filaments. Ooplasmic segregation in Nereis virens may be considered as a primitive form of ooplasmic segregation in Annelida.

Animals↗

[Studies on the distorted segregation of foreign genes in transgenic rice progenies].

The segregation mode of transgenes was investigated in the transgenic progenies of three rice varieties (lines) produced by Agrobacterium-mediated transformation. The transgenic lines all contained the Bacillus thuringiensis cry1Ab gene, under the control of a maize ubiquitin promoter, and linked in tandem with gusA and hpt genes. PCR analysis showed the transgenes cry1Ab and gusA co-segregated in all self and crossed progenies tested. Therefore, GUS bio-assay of leaf or endosperm tissues was used to monitor transgene segregation in the experiment. It was found that the ratio of positive to negative plants was significantly smaller than 3:1 in all heterozygous plants derived progenies, which implied the segregation biased from typical Mendelian mode for a single dominant gene. Less GUS positive plants, and consequently less homozygous transgenic lines than expected were recovered from the self progenies. Transgenic heterozygous plants (+/-) were crossed as female or male parent to conventional rice varieties (-/-), and the ratio of gusA positive (+/-) to negative (-/-) plants was investigated in test F1 population. When used as female parent, the segregation fit to 1:1, but significantly smaller than 1:1 when used as male parent. The seed-set of transgenic Nipponbare progeny was investigated individually for GUS positive and negative plants. It was found that the positive plants had an average seed-set of 64.5%, significantly lower than that of negative plants (77.9%). The biological and genetic basis of distorted segregation of transgenes was discussed and deduced on the basis of above results, and the authors are inclined to ascribe these phenomena to the poor competitive ability of pollens carrying transgenes.

Bacillus thuringiensis Toxins↗

Segregation of presynaptic inputs on an identified target neuron in vitro: structural remodeling visualized over time.

Sensory cells of Aplysia form chemical synapses with the motor cell L7 in culture. Under certain conditions, sensory cells will also form electrical connections with each other. Sites of chemical synaptic interaction between the sensory cells and L7 are located at varicosities along sensory cell processes that overlie the main axons of L7, since these structures have been shown ultrastructurally to contain active zones. Previous studies have suggested that the distribution of sensory cell varicosities can be restricted to exclusive regions of the motor cell by the presence of other sensory cells. We wished to investigate (1) how this segregated pattern is generated over time and (2) whether electrical coupling between sensory cells has an effect on this segregated pattern. Using fluorescent dye injection and low-light video microscopy, we visualized the distribution of varicosities for each of two sensory cells growing on L7. In cases in which sensory cells are not electrically coupled, the varicosities from these two cells are spatially segregated on the target after 4 d in culture but not after 2 d in culture. Examination of the varicosity distribution of the same sensory cells on the second and third day of growth indicated both an increased rate in the elimination of varicosities from previously occupied areas and a restriction of varicosity formation in new areas of the target when a second sensory cell is present. For sensory cells that are electrically coupled, varicosities from these cells were not spatially segregated on the target even after 4 d in culture. These observations in vitro suggest that segregation of synaptic inputs by Aplysia sensory cells, which show little spontaneous activity of action potentials, can emerge over time via a process that includes both the elimination of existing sensory varicosities and the restriction of new varicosity formation. Our results also suggest that electrical connections between presynaptic cells can disrupt the segregation of their varicosities on a target, resulting in significant changes in the developing connectivity.

Animals↗

Identifying pedigrees segregating at a major locus for a quantitative trait: an efficient strategy for linkage analysis.

Having found evidence for segregation at a major locus for a quantitative trait, a logical next step is to identify those pedigrees in which major-locus segregation is occurring. If the quantitative trait is a risk factor for an associated disease, identifying such segregating pedigrees can be important in classifying families by etiology, in risk assessment, and in suggesting treatment modalities. Identifying segregating pedigrees can also be helpful in selecting pedigrees to include in a subsequent linkage study to map the major locus. Here, we describe a strategy to identify pedigrees segregating at a major locus for a quantitative trait. We apply this pedigree selection strategy to simulated data generated under a major-locus or mixed model with a rare dominant allele and sampled according to one of several fixed-structure or sequential sampling designs. We demonstrate that for the situations considered, the pedigree selection strategy is sensitive and specific and that a linkage study based only on the pedigrees classified as segregating extracts essentially all the linkage information in the entire sample of pedigrees. Our results suggest that for large-scale linkage studies involving many genetic markers, the savings from this strategy can be substantial and that, compared with fixed-structure sampling, sequential sampling of pedigrees can greatly improve the efficiency for linkage analysis of a quantitative trait.

Genetic Linkage↗

Eye-specific segregation requires neural activity in three-eyed Rana pipiens.

The addition of a third eye primordium to the forebrain region of a Rana pipiens embryo invariably results in the development of a series of periodic, mutually exclusive eye-specific bands in tectal lobes dually innervated by the host and supernumerary fibers. A number of investigators have proposed that such source-specific segregation arises as a compromise between two mechanisms that are normally involved in retinotectal map formation: one which is dependent on cell surface affinities to align the map and produce a rough retinotopy and a second that "fine tunes" the map by stabilizing adjacent terminals from neighboring retinal ganglion cell bodies at the expense of terminals from non-neighboring cells. In this study we have tested the idea that this second "fine-tuning" mechanism is dependent on neural activity by blocking impulse activity in the optic nerves of three-eyed tadpoles. To assess the requirement for activity on the formation of bands, both normal optic nerves of 17 three-eyed tadpoles were crushed intraorbitally. Two weeks after this operation, the supernumerary retinal projection had debanded and spread to cover the entire tectum in a continuous fashion. By 4 weeks, however, the host optic fibers regenerated back to the tecta and began to form segregated stripes with the fibers from the third eye. Six to 7 weeks after the optic nerve crush the periodic pattern of eye-specific segregation characteristic of dually innervated tecta was again pronounced. When activity in all three optic nerves was eliminated with tetrodotoxin (TTX; embedded in a slow release plastic) during the last 3 weeks of this process, the fibers from the two competing eyes failed to segregate and, instead, formed two completely overlapping, continuous projections across the tectal surface. To test for the requirement of activity in the maintenance of segregation, we also subjected three-eyed tadpoles without optic nerve crush to TTX blockade for 2, 3, and 4 weeks. Animals sacrificed at 2 weeks show overlap of the projections in the rostral tectum but distinct interdigitating stripes in other regions of these lobes. After 3 weeks of blockade, segregation of the projections was less distinct in the central tectum as well. After 4 weeks of TTX blockade the terminals from both eyes spread to form continuous overlapping projections throughout the tectum. Examination of well isolated, individual retinal ganglion cell terminal arbors during this period reveals that they occupy a significantly greater area of tectum following the TTX treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗