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Results for “balancing selection”

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PubMed2026

Intra-colony divergence and global allele sharing reflect purifying selection and recombination at the Botryllus histocompatibility factor locus.

Urochordates, the closest relatives of vertebrates, lack adaptive immunity. However, some taxa, such as the colonial species Botryllus schlosseri, provide a unique model for studying innate self/non-self recognition through natural allogeneic transplantation responses. In this species, interactions between colonies are controlled by a highly polymorphic locus, with the Botryllus histocompatibility factor (BHF) being the only gene known to predict tissue fusion or rejection outcomes with complete accuracy. Here, we analyzed full-length BHF alleles from 19 laboratory-born and wild colonies and found that highly divergent alleles tend to coexist within individuals, whereas identical alleles can be shared across continental-scale distances. Despite extensive length variation, evidence of intragenic recombination, and pronounced nucleotide diversity, BHF exhibits limited protein divergence, with 33 alleles encoding only 17 distinct protein variants. Contrary to expectations for polymorphic recognition genes, no evidence of balancing or directional selection was detected. Instead, signatures of purifying selection were observed. We propose that this contrast between nucleotide and protein diversity arises from the combined effects of recombination, human-mediated gene flow, and linkage to nearby loci under balancing selection, while functional constraints maintain protein stability. These findings suggest that extensive protein diversification may not be a universal driver of allorecognition gene evolution.

Animals↗

PubMed2006

Selection on the human immunodeficiency virus type 1 proteome following primary infection.

Typically during human immunodeficiency virus type 1 (HIV-1) infection, a nearly homogeneous viral population first emerges and then diversifies over time due to selective forces that are poorly understood. To identify these forces, we conducted an intensive longitudinal study of viral genetic changes and T-cell immunity in one subject at < or =17 time points during his first 3 years of infection, and in his infecting partner near the time of transmission. Autologous peptides covering amino acid sites inferred to be under positive selection were powerful for identifying HIV-1-specific cytotoxic-T-lymphocyte (CTL) epitopes. Positive selection and mutations resulting in escape from CTLs occurred across the viral proteome. We detected 25 CTL epitopes, including 14 previously unreported. Seven new epitopes mapped to the viral Env protein, emphasizing Env as a major target of CTLs. One-third of the selected sites were associated with epitopic mutational escapes from CTLs. Most of these resulted from replacement with amino acids found at low database frequency. Another one-third represented acquisition of amino acids found at high database frequency, suggesting potential reversions of CTL epitopic sites recognized by the immune system of the transmitting partner and mutation toward improved viral fitness in the absence of immune targeting within the recipient. A majority of the remaining selected sites occurred in the envelope protein and may have been subjected to humoral immune selection. Hence, a majority of the amino acids undergoing selection in this subject appeared to result from fitness-balanced CTL selection, confirming CTLs as a dominant selective force in HIV-1 infection.

Amino Acid Sequence↗

PubMed2005

Convergent evolution and divergent selection: lizards at the White Sands ecotone.

Ecological transition zones, where organismal phenotypes result from a delicate balance between selection and migration, highlight the interplay of local adaptation and gene flow. Here, I study the response of an entire species assemblage to natural selection across a common ecotone. Three lizard species, distributed along a dramatic environmental gradient in substrate color, display convergent adaptation of blanched coloration on the gypsum dunes of White Sands National Monument. I investigate the role of gene flow in modulating phenotypic response to selection by quantifying color variation and genetic variation across the ecotone. I find species differences in degree of background matching and in genetic connectivity of populations across the ecotone. Differences among species in phenotypic response to selection scale precisely to levels of genetic isolation. Species with higher levels of gene flow across the ecotone exhibit less dramatic responses to selection. Results also reveal a strong signal of ecologically mediated divergence for White Sands lizards. For all species, phenotypic variation is better explained by habitat similarity than genetic similarity. Convergent evolution of blanched coloration at White Sands clearly reflects the action of strong divergent selection; however, adaptive response appears to be modulated by gene flow and demographic history and can be predicted by divergence-with-gene-flow models.

Animals↗

PubMed2001

Evolution of genome-phenome diversity under environmental stress.

The genomic era revolutionized evolutionary biology. The enigma of genotypic-phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975. We explored the following questions. (i) How much of the genomic and phenomic diversity in nature is adaptive and processed by natural selection? (ii) What is the origin and evolution of adaptation and speciation processes under spatiotemporal variables and stressful macrogeographic and microgeographic environments? We advanced ecological genetics into ecological genomics and analyzed globally ecological, demographic, and life history variables in 1,200 diverse species across life, thousands of populations, and tens of thousands of individuals tested mostly for allozyme and partly for DNA diversity. Likewise, we tested thermal, chemical, climatic, and biotic stresses in several model organisms. Recently, we introduced genetic maps and quantitative trait loci to elucidate the genetic basis of adaptation and speciation. The genome-phenome holistic model was deciphered by the global regressive, progressive, and convergent evolution of subterranean mammals. Our results indicate abundant genotypic and phenotypic diversity in nature. The organization and evolution of molecular and organismal diversity in nature at global, regional, and local scales are nonrandom and structured; display regularities across life; and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection, including diversifying, balancing, cyclical, and purifying selective regimes, interacting with, but ultimately overriding, the effects of mutation, migration, and stochasticity.

Animals↗

PubMed1988

Selenium balance studies in apparently healthy and housebound elderly people eating self-selected diets.

1. Metabolic balance studies (5 d) for Se were conducted in twenty-four apparently healthy elderly people (age 69.6-85.4 years), and twenty housebound subjects (age 69.9-85.1 years) with chronic disease. During the study the subjects lived in their own homes, ate self-selected diets and continued their normal daily activities. 2. Geometric mean daily dietary intakes of the two groups were significantly different (P less than 0.01), being 819 (range 310-1631) nmol for the healthy and 475 (range 233-1136) nmol for the housebound elderly. 3. Daily intake of Se significantly correlated with balance in both groups. Solution of the regression equations gave theoretical daily requirements of 447 nmol for the healthy and 419 nmol for the housebound subjects. The healthy elderly were in positive balance of 148 nmol/d for Se and the housebound were in equilibrium with an overall mean retention of 43 nmol/d. 4. Mean levels of Se in blood fractions for the healthy and housebound subjects were significantly different, being 1.65 and 1.40 mumol/l whole blood, 1.45 and 1.21 mumol/l plasma and 5.72 and 5.30 nmol/g haemoglobin in erythrocytes respectively. There was no difference in the whole-blood glutathione peroxidase (EC 1.11.1.9) activities between the two groups. 5. There were clear differences in Se status between the two groups of elderly people. The cause of the positive balance in the healthy subjects remains unexplained.

Aged↗

PubMed2006

Stable genetic polymorphism in heterogeneous environments: balance between asymmetrical dispersal and selection in the acorn barnacle.

Elucidating the processes responsible for maintaining polymorphism at ecologically relevant genes is intimately related to understanding the interplay between selection imposed by habitat heterogeneity and a species' capacity for dispersal in the face of environmental constraints. In this paper, we used a model-based approach to solve equilibria of balanced polymorphism, given values of fitness and larval dispersal among different habitats in the acorn barnacle Semibalanus balanoides from the Gulf of St Lawrence. Our results showed that allele frequencies observed at both MPI* and GPI* loci represented stable equilibria, given empirical estimates of fitness values, and that considerably more larvae dispersed from one region (north) to the other (south) than vice versa. Dispersal conditions were predicted to be similar for the maintenance of polymorphism at both loci. Moreover, the values of asymmetrical dispersal required by the model to reach stable equilibria were compatible with empirical estimates of larval dispersal and oceanic circulation documented in this system. Overall, this study illustrated the usefulness of a modified and computable version of Bulmer's model (1972) in order to test hypotheses of balanced polymorphism resulting from interactions between spatial selection and asymmetrical dispersal.

Animals↗

PubMed2002

Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 2. Emissions.

Accurate and complete data on the global atmospheric releases (emissions) of individual PCB congeners are essential to study source-receptor relationships and contamination patterns in remote areas, such as the Arctic. Information on the anthropogenic emissions may also be useful for the interpretation of measured levels and patterns of atmospheric PCBs. This study builds upon an accompanying paper, presenting an estimate of the global historical production and consumption of 22 PCB congeners (Breivik K, Sweetman A, Pacyna JM, Jones KC. Towards a global historical emission inventory for selected PCB congeners--a mass balance approach. 1. Global production and consumption. Sci Total Environ, submitted). Here, a dynamic mass balance model is elaborated, parameterised and applied in an attempt to estimate the historical anthropogenic emissions as a direct result of the widespread usage of PCBs for a period of 70 years. This paper presents details of the mass balance approach, along with a discussion of the major uncertainties. It is shown that the diversity of historical usage, disposal and accidental release pathways makes it an extremely difficult task to bridge the gap between consumption and emissions, resulting in an equally complex and diverse true emission pattern. These results may therefore at best represent order-of-magnitude estimates only and the results in absolute terms should be treated with great caution. In spite of these uncertainties, useful information can still be gained. The results suggest that temperature is an extremely important factor controlling both emission amount as well as the emission pattern of PCBs. In particular, the emissions of the more chlorinated (and persistent) PCB congeners appear to be significantly influenced by (uncontrolled) high-temperature sources. As a consequence, it may prove warranted to undertake further measures to avoid that contaminated materials are subject to elevated temperatures and uncontrolled burning. It is furthermore suggested that efforts should be directed towards a better characterisation and quantification of these potentially important release pathways. In addition, alternative approaches to bridge the gap between consumption and emissions in quantitative terms should be considered in order to improve these estimates.

Arctic Regions↗

PubMed2003

Epistasis in polygenic traits and the evolution of genetic architecture under stabilizing selection.

We consider the effects of epistasis in a polygenic trait in the balance of mutation and stabilizing selection. The main issues are the genetic variation maintained in equilibrium and the evolution of the mutational effect distribution. The model assumes symmetric mutation and a continuum of alleles at all loci. Epistasis is modeled proportional to pairwise products of the single-locus effects. A general analytical formalism is developed. Assuming linkage equilibrium, we derive results for the equilibrium mutation load and the genetic and mutational variance in the house of cards and the Gaussian approximation. The additive genetic variation maintained in mutation-selection balance is reduced by any pattern of the epistatic interactions. The mutational variance, in contrast, is often increased. Large differences in mutational effects among loci emerge, and a negative correlation among (standard mean) locus mutation effects and mutation rates is predicted. Contrary to the common view since Waddington, we find that stabilizing selection in general does not lead to canalization of the trait. We propose that canalization as a target of selection instead occurs at the genic level. Here, primarily genes with a high mutation rate are buffered, often at the cost of decanalization of other genes. An intuitive interpretation of this view is given in the discussion.

Epistasis, Genetic↗

PubMed1997

The design of adaptive systems: optimal parameters for variation and selection in learning and development.

Some aspects of learning and development are based on evolutionary change within the organism. In trial and error learning, variant ideas or behaviors are generated and selective filters (learning rules) choose among the population of variants. Development may, in some cases, proceed by selection within a population of variant cellular lineages. This paper analyses abstract properties of selective systems to understand the evolutionary dynamics that occur within organisms. The Price Equation and Fisher's fundamental theorem of natural selection, two of the most powerful concepts in evolutionary genetics, are applied in a general way to internal selective systems in learning and development. This analysis emphasizes generative mechanisms and selective filters as genetically controlled phenotypes of individual organisms. Generative mechanisms create the variation on which selection acts. Selective filters determine the extent to which selection within the organism optimizes organismal performance. The methods of Price and Fisher provide a general way in which to partition evolutionary change into improvements caused by selection and the tendency of high performance variants to deteriorate because of competition or environmental change. This balance between selective improvement, at a rate equal to the variance in fitness, and a matching deterioration in performance, provides general insight into the common properties of adaptive systems in genetics, learning and development. These ideas are applied to a model of honey bee foraging. This example clarifies the relation between genes and phenotypes controlled by internal selective systems.

Adaptation, Physiological↗

PubMed2005

Influence of surfactant molecular structure on two-dimensional surfactant-DNA complexes: Langmuir balance study.

In this paper, we used two simplified methods to understand the influence of surfactant molecular structure on the properties of surfactant-DNA complexes. First, we selected Langmuir balance technique, a two-dimensional (2D) method, which allows complex formation under equilibrium-like conditions, avoiding some of the inherent problems involved in solution. Secondly, two series of simple quaternary ammonium surfactants were used. The cationic surfactant-DNA complex monolayers were formed at the air-water interface through the electrostatic interaction between the ammonium groups of the surfactants and the phosphate groups of DNA at the air-water interface. Combining the results of pi-A isotherms, pi-t isotherms, and atomic force microscopy (AFM) measurements, it was found that the surfactant molecular structures affect the surface properties and morphologies of 2D surfactant-DNA complexes. We expect that the study of the properties of 2D surfactant-DNA complexes will help us to understand the physicochemical properties of surfactant-DNA complexes, which are important for gene delivery.

Aluminum Silicates↗

PubMed2000

Opposing levels of selection can cause neutrality: mating patterns and maternal-fetal interactions.

A biallelic viability model based on human data for maternal-fetal interactions reported by Hedrick (1997) gives the interesting result of neutral stability at all gene frequencies. I show that there are two levels of selection, within and among families, acting in opposing directions in this model and that the neutral stability occurs when the two levels of selection exactly balance one another, as they do in a randomly mating population. Deviations from random mating disrupt the balance and consequently destroy the neutral stability. However, with inbreeding avoidance, which characterizes the human histocompatibility loci, within-family selection is strengthened and among-family selection is weakened. This favors the invasion of new alleles and contributes to a high equilibrium level of genetic diversity at loci with maternal-fetal interactions affecting offspring viability in the pattern described by Hedrick. This pattern of selection is remarkably similar to that observed for the maternal effect selfish genes, Medea in flour beetles and scat in the mouse, and the Gp-9 gene in the fire ant.

Alleles↗

PubMed1998

Dynamic balance of segregation distortion and selection maintains normal allele sizes at the myotonic dystrophy locus.

Myotonic dystrophy (DM), an autosomal dominant neurological disorder, is caused by CTG-repeat expansions at the DMPK locus, with affected individuals having > or = 50 repeats of this trinucleotide. Reduced reproductive fitness of affected individuals and decreased viability of congenital DM have been noted. Expanded CTG-repeat alleles are highly unstable, predominantly yielding even higher repeat sizes. Preferential transmission of longer alleles from heterozygous mothers within the normal size range of alleles also is observed. In view of these observations, it is worth examining how DM has been maintained in human populations for hundreds of generations. We present an analysis of the dynamic properties of a model of joint effects of segregation distortion and selection (intensity of which increases with allele sizes of an individual's genotype). Our mathematical formulation and numerical analyses demonstrate that a weak segregation distortion during female meiosis, together with selection of comparable intensity (within the normal allele size range), can maintain an equilibrium distribution of allele frequencies. Genetic drift, acting in conjunction with the occasional contraction of alleles by mutation, can contribute to the balance of segregation distortion and mutation, in the sense that even weaker selection can explain the observed allele frequencies. The model is applied to CTG-repeat size distributions at the DMPK locus, observed in normal individuals from world populations.

Alleles↗

PubMed1996

Factors affecting sample selection in a randomized trial of balance enhancement: the FICSIT Study.

OBJECTIVE: To determine demographic, functional, and health-related factors that may have influenced the selection of older adults for a randomized trial of balance enhancement. DESIGN: Comparison of participants with nonparticipants at various stages of the recruiting process. SETTING: Northeastern suburban community. PARTICIPANTS: Registered voters aged 75 and older (n = 7191). MEASUREMENTS: Demographic, health-related, functional, balance, gait, and falling characteristics. RESULTS: The overall participation rate in the randomized trial was 1.5%. Compared with nonparticipants, participants were significantly more likely to be male, married, living with others, living in a house, highly educated, healthy, and physically active. CONCLUSION: Recruiting older subjects by mail to studies of rigorous interventions can produce significant selection biases that may limit the population to which results can be generalized.

Accidental Falls↗

PubMed2003

Predictions of recall and study strategy decisions after diffuse brain injury.

OBJECTIVE: To investigate relationships between self-monitoring operationalized by predicting recall and study strategy decisions made by adults with diffuse, acquired brain injury (ABI) and adults without ABI. RESEARCH DESIGN AND METHODS: Eighteen adults with ABI and 16 without ABI studied two lists of unrelated noun-pairs, made item-by-item immediate and delayed recall predictions and selected items (after predictions) to restudy again. The computer selected items for restudy based on the lowest prediction rating (i.e. unlikely to recall). A mixed list design was used to balance item selection (self or computer,within-lists) by type of prediction (immediate or delayed, between-lists). Recall was tested prior to and after restudying. HYPOTHESES: Delayed recall predictions would be more accurate than immediate recall predictions; participants would select items for restudy that corresponded with 'lower' delayed predictions (i.e. less likely to recall) and 'higher' immediate predictions (i.e. more likely to recall); for adults with ABI, recall would improve the most from restudying items selected after delayed predictions; and that recall predictive accuracy and study selection decisions are independent processes. RESULTS: Delayed recall predictions were more accurate than immediate recall predictions, though adults with ABI tended to be less accurate than controls. Both groups selected items for restudy that had relatively low prediction ratings irrespective of prediction timing. Of adults with ABI, those with low recall prior to restudy selected items that had 'high' immediate predictions (i.e. likely to recall). However, there was no greater benefit to recall using this strategy. For adults with ABI, recall improved the most from restudying items that were self-selected after delayed predictions, whereas controls' recall improved, irrespective of prediction and selection timing. Between-person correlations revealed no relationship between recall predictive accuracy and study selection strategies. CONCLUSIONS: These findings imply that adults with ABI should base strategy decisions on delayed predictions rather than on 'in the moment' immediate ones, selecting items that they have predicted will be difficult to recall. Continued efforts to disambiguate self-monitoring from strategy decisions are required before direct clinical applications can be made.

Adult↗

PubMed1992

Interferon-alpha-induced gene expression: evidence for a selective effect of ouabain on activation of the ISGF3 transcription complex.

Binding of interferons (IFNs) to their cell surface receptors stimulates rapid translocation of cytoplasmic proteins to the nucleus and the expression of a variety of cellular genes within minutes. Translocated proteins subsequently bind to the interferon-stimulated response element (ISRE) located in the promoters of all IFN-activated cellular genes. We report here that ouabain, a specific inhibitor of the Na/K ATPase, selectively inhibited transcription of several IFN-alpha-induced cellular RNAs under conditions in which some other well-described signal transduction pathways remained intact. The latter included induction of human metallothionein 2A (HMT2A) by phorbol ester and induction of IP-10 RNA by IFN-gamma. Ouabain itself induced RNA of the protooncogene c-fos which conversely was inhibited by IFN-alpha. Specificity of the ouabain effects on IFN alpha-induced RNAs with respect to a direct action on the Na/K ATPase was shown with a transfected monkey CV-1 cell line which expresses the ouabain-insensitive rat alpha 1 subunit. Electrophoretic mobility shift assays (EMSAs) using nuclear extracts from ouabain-treated cells demonstrated that ouabain decreased IFN alpha-induced binding of the ISGF3 complex to the ISRE. Reconstitution experiments showed that this effect of ouabain is not due to the inhibition of IFN alpha activation of the ISGF3 alpha subcomponent, which occurs in the cytoplasm, but a selective depletion of the ISGF3 gamma factor which in concert with activated ISGF3 alpha induces interferon-stimulated gene (54 kDa) transcription. These findings imply that intracellular ion balance can selectively regulate the half-life of the ISGF3 gamma protein or the ability of this protein to complex with ISGF3 alpha to activate IFN alpha-regulated cellular genes.

Base Sequence↗

PubMedDate not supplied

Clinical aspects of COX-2 inhibitors.

Inflammation is the body's response to tissue damage. The signs of inflammation are pain, swelling and edema. One of the major chemical mediators involved in the inflammatory response is the group of prostaglandins (PGs) synthesized by the enzyme cyclooxygenase (COX). There are two isoforms of COX, the constitutive enzyme COX-1, which is responsible for the production of PGs with general housekeeping functions such as maintenance of renal perfusion and a protective effect on the gastric mucosa against ulceration; and the inducible enzyme COX-2, which is responsible for the production of proinflammatory PGs. Non-steroidal antiinflammatory drugs (NSAIDs), by inhibiting the COX enzyme, are able to reduce the pain and swelling associated with inflammation. In theory, new molecules that preferentially inhibit the inducible enzyme alone would not affect the housekeeping function of COX-1 but would retain the antiinflammatory action. Currently, there are a number of molecules available which claim to have some selectivity for the COX-2 enzyme. These have been labeled COX-2 preferential drugs. Highly selective COX-2 enzyme inhibitors are being assessed in phase II and phase III clinical studies. What are the issues these drugs will create and will they be successful? The first question is whether they are truly COX-2-selective. The balance of evidence suggests that they are. There is less gastric ulceration by the preferential drugs and there is very little evidence of gastric damage with the COX-2-selective drugs. All these drugs seem to maintain renal perfusion better than other NSAIDs and platelet aggregation is not affected. The second question is whether these drugs are as effective as conventional NSAIDs. From the preliminary data available it appears that the inhibition of COX-2 is effective in reducing inflammation. There are some doubts from studies in animal models as to whether some inhibition of COX-1 is also required, but this has not yet been shown in humans. There are concerns regarding the cerebral function of COX-2 and the expression of COX-2 in the kidney and gut. Thirdly, will new benefits arise from the use of these drugs? It seems likely that selective COX-2 inhibition will have the same beneficial effects on Alzheimer's disease and colonic cancer as nonselective drugs. In fact, these may even become new indications. What are the likely hazards? There will probably be individual problems with particular drugs but these cannot be predicted. The crucial issue is that patients who benefit most from NSAIDs are those who will be most likely to have side effects from the nonselective COX-1 and COX-2 inhibitors. Therefore, once there is good evidence of their efficacy and safety they will become widely used drugs.

Journal Article↗

PubMed2006

Topological relationships between brain and social networks.

Brains are complex networks. Previously, we revealed that specific connected structures are either significantly abundant or rare in cortical networks. However, it remains unknown whether systems from other disciplines have similar architectures to brains. By applying network-theoretical methods, here we show topological similarities between brain and social networks. We found that the statistical relevance of specific tied structures differs between social "friendship" and "disliking" networks, suggesting relation-type-specific topology of social networks. Surprisingly, overrepresented connected structures in brain networks are more similar to those in the friendship networks than to those in other networks. We found that balanced and imbalanced reciprocal connections between nodes are significantly abundant and rare, respectively, whereas these results are unpredictable by simply counting mutual connections. We interpret these results as evidence of positive selection of balanced mutuality between nodes. These results also imply the existence of underlying common principles behind the organization of brain and social networks.

Animals↗

PubMed1984

Dietary selenium levels needed to maintain balance in North American adults consuming self-selected diets.

Dietary selenium intake and selenium balance were measured during 4 1-wk metabolic periods over the course of 12 months in 27 free-living adult volunteers consuming self-selected diets. Men consumed more selenium in their diets than women (90 +/- 4 versus 74 +/- 3 micrograms/day), but plasma selenium levels were similar for both sexes (136 +/- 4 versus 133 +/- 4 ng/ml, respectively). Neither dietary selenium intake nor plasma selenium levels varied seasonally. Regression of selenium balance versus intake indicated that adult men needed 80 micrograms SE/day to stay in balance, whereas women needed only 57 micrograms SE/day. When balance and intake were adjusted for body weight, the sex difference disappeared, and both men and women needed about 1 microgram of dietary selenium per kg of body weight per day to maintain balance. The levels of dietary selenium reported here as necessary to maintain balance in North American adults are considerably higher than those previously reported as needed for balance in adult women from New Zealand, a country where low selenium status is common. Our results indicate that the levels of dietary selenium needed to achieve balance are a function of lean body mass and historical selenium intake.

Adult↗