SEARCH · PubMed Health

Results for “balancing selection”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources

PubMed2003

Viabilities of originally natural O-chromosomal inversion homo- and heterokaryotypes in Drosophila subobscura.

The influence of epistatic interactions of lethal and non-lethal genes upon viability of Drosophila inversion karyotypes is poorly known. In this paper we present comparative results for viabilities of 21 originally natural O-inversion homo- and 38 heterokaryotypes in a D. subobscura population. We observed strong heterotic effect in viability of O-lethal heterozygotes irrespective of different inversion backgrounds, which indicates a mechanism for protection of a great number of lethal genes. In O-non-lethal heterozygotes the heterotic effect in viability was absent irrespective of different inversion backgrounds. Our results showed a great extent of genetic load and high abundance of O-chromosomal arrangements in the population analyzed. It belongs to the set of central European populations. An epistasis of lethal genes present in O-inversion hetero- and not present in O-inversion homokaryotypes of moderate or low frequencies could be good example for co-adaptation of chromosomal inversions with regard to the genetic load. This represents a more efficient mechanism for limitation of genetic load than alternative mechanisms for protection of lethals. Except for lethal genes, possible epistatic interactions of mildly deleterious (subvital) genes, could also be responsible for limiting the extent of genetic load in natural D. subobscura populations. We demonstrated a non-random distribution of several combinations of viability classes among different O-inversion homo- and heterokaryotypes. As a consequence of that, the viabilities of the O-inversion homokaryotypes compared to heterokaryotypes were significantly higher at low frequencies than in moderate or high frequencies. This shows frequency-dependence as a mechanism of balancing selection for protection of O-chromosomal inversions in natural D. subobscura populations. In addition, the viabilities of the O-inversion homokaryotypes of lower frequency, compared to homokaryotypes of moderate or high frequency, were significantly higher. This again indicates the existence of supergene selection as another mechanism for protection of chromosomal inversions, as co-adapted complexes in natural D. subobscura populations.

Animals↗

PubMed2006

HLA class II gene polymorphism in Parsees and Zoroastrians of Iran.

Extensive polymorphism of the HLA genes in different ethnic groups has been used as an invaluable tool for anthropological studies. In this study, HLA-DRB1, DQA1 and DQB1 allele frequencies and haplotypes were determined in 72 Parsees and 65 Zoroastrians living in Iran. The predominant DRB1 allele was *1103 = 4 in Parsees and *0701 in Zoroastrians. DQA1*0501 was the most common alleles in both spopulations. The most frequent DQB1 allele was *0301 in Parsees and *0201 in Zoroastrians. DRB1*1103 = 4-DQA1*0501-DQB1*0301 and DRB1*0701-DQA1*0201-DQB1*0201 were the most prevalent haplotypes in Parsees and Zoroastrians, respectively. Significant deviation from Hardy-Weinberg equilibrium was observed in DQA1 and DQB1 loci of Zoroastrians. The former locus also departed from neutrality due to balancing selection. All pairs of the studied loci in this study showed significant linkage disequilibrium. Analysis of molecular variance indicated that the main variation was confined to individuals within the studied populations. Neighbour-joining tree based on Nei's genetic distances according to DRB1 and DQB1 allele frequencies showed that Parsees and Zoroastrians of Iran were located in the same cluster of the phylogenetic tree. Furthermore, Zoroastrians of Iran and Pakistan are very close to each other. This study will serve as a reference for further anthropological studies when the HLA profile of all ethnic groups of Iran is investigated.

Ethnicity↗

PubMed2006

Genetic population structure of the soil bacterium Myxococcus xanthus at the centimeter scale.

Myxococcus xanthus is a gram-negative soil bacterium best known for its remarkable life history of social swarming, social predation, and multicellular fruiting body formation. Very little is known about genetic diversity within this species or how social strategies might vary among neighboring strains at small spatial scales. To investigate the small-scale population structure of M. xanthus, 78 clones were isolated from a patch of soil (16 by 16 cm) in Tübingen, Germany. Among these isolates, 21 genotypes could be distinguished from a concatemer of three gene fragments: csgA (developmental C signal), fibA (extracellular matrix-associated zinc metalloprotease), and pilA (the pilin subunit of type IV pili). Accumulation curves showed that most of the diversity present at this scale was sampled. The pilA gene contains both conserved and highly variable regions, and two frequency-distribution tests provide evidence for balancing selection on this gene. The functional domains in the csgA gene were found to be conserved. Three instances of lateral gene transfer could be inferred from a comparison of individual gene phylogenies, but no evidence was found for linkage equilibrium, supporting the view that M. xanthus evolution is largely clonal. This study shows that M. xanthus is surrounded by a variety of distinct conspecifics in its natural soil habitat at a spatial scale at which encounters among genotypes are likely.

Bacterial Proteins↗

PubMed2005

Evolution of transcription regulatory genes is linked to niche specialization in the bacterial pathogen Streptococcus pyogenes.

Streptococcus pyogenes is a highly prevalent bacterial pathogen, most often giving rise to superficial infections at the throat or skin of its human host. Three genotype-defined subpopulations of strains exhibiting strong tropisms for either the throat or skin (specialists) or having no obvious tissue site preference (generalists) are recognized. Since the microenvironments at the throat and skin are distinct, the signal transduction pathways leading to the control of gene expression may also differ for throat versus skin strains of S. pyogenes. Two loci (mga and rofA/nra) encoding global regulators of virulence gene expression are positioned 300 kb apart on the genome; each contains alleles forming two major sequence clusters of approximately 25 to 30% divergence that are under balancing selection. Strong linkage disequilibrium is observed between sequence clusters of the transcription regulatory loci and the subpopulations of throat and skin specialists, against a background of high recombination rates among housekeeping genes. A taxonomically distinct commensal species (Streptococcus dysgalactiae subspecies equisimilus) shares highly homologous rof alleles. The findings provide strong support for a mechanism underlying niche specialization that involves orthologous replacement of regulatory genes following interspecies horizontal transfer, although the directionality of gene exchange remains unknown.

Bacterial Proteins↗

PubMed2003

Hybridization and introgression of the genomes of Drosophila nasuta and Drosophila albomicans: evolution of new karyotypes.

Drosophila nasuta (2n = 8) and Drosophila albomicans (2n = 6) are cross-fertile allopatric sibling chromosomal races of the nasuta subgroup of Drosophila. Hybrids of these races can be maintained for any number of generations. Some of the introgressed hybrid lineages of D. nasuta and D. albomicans, after passing through a transient phase of karyotypic polymorphism, ended up with a stable karyotype whose composition is different from those of the parental races. Such hybrid populations were called cytoraces, in which the chromosomes of D. nasuta and D. albomicans are represented in different combinations. The karyotypic composition of 16 such cytoraces have been presented and discussed with reference to evolutionary strategies such as balancing selection, directional selection, and sex-specific effect on different components of the evolving karyotypes.

Animals↗

PubMed1979

Electrophoretic variation and differentiation in four strains of domesticated rainbow trout (Salmo gairdneri).

A total of 1462 rainbow trout (Salmo gairdneri Richardson) representing four California domestic strains, were examined electrophoretically at 24 gene loci to investigate the amount of genetic variability within strains and genetic differentiation between strains, relative to wild populations. Estimated heterozygosities of 0.071 to 0.134 were similar to those reported for wild populations and thus indicated that the domestic strains were at least as variable as wild populations. Genetic distances between strains ranged from 0.011 to 0.067, values typical of the level of differentiation observed between local conspecific populations in a variety of organisms. It was suggested that this high level of heterozygosity is due to mixing of populations in the strains' histories and perhaps also to balancing selection.

Albumins↗

PubMed2000

Genetic perspectives on human origins and differentiation.

This is a review of genetic evidence about the ancient demography of the ancestors of our species and about the genesis of worldwide human diversity. The issue of whether or not a population size bottleneck occurred among our ancestors is under debate among geneticists as well as among anthropologists. The bottleneck, if it occurred, would confirm the Garden of Eden (GOE) model of the origin of modern humans. The competing model, multiregional evolution (MRE), posits that the number of human ancestors has been large, occupying much of the temperate Old World for the last two million years. While several classes of genetic marker seem to contain a strong signal of demographic recovery from a small number of ancestors, other nuclear loci show no such signal. The pattern at these loci is compatible with the existence of widespread balancing selection in humans. The study of human diversity at (putatively) neutral genetic marker loci has been hampered since the beginning by ascertainment bias since they were discovered in Europeans. The high levels of polymorphism at microsatellite loci means that they are free of this bias. Microsatellites exhibit a clear almost linear diversity gradient away from Africa, so that New World populations are approximately 15% less diverse than African populations. This pattern is not compatible with a model of a single large population expansion and colonization of most of the Earth by our ancestors but suggests, instead, gradual loss of diversity in successive colonization bottlenecks as our species grew and spread.

Animals↗

PubMed2000

Curt Richter and regulatory physiology.

Curt Richter made seminal contributions to our understanding of a number of issues regarding the relationships between physiology and behavior. He was the first to conceptualize behavior as an aspect of regulatory physiology. These ideas developed from his work on behavioral responses to a variety of physiological perturbations. The classic example is Richter's demonstration of the development of avid sodium ingestion in response to urinary sodium loss after adrenalectomy. Some of Richter's ideas on the nature and underlying physiology of specific appetites maintain their influence and continue to stimulate active investigation. Others, focused on abilities to self-select balanced diets, have not borne the test of time or experimental challenge. As current research takes a more molecular focus, Richter's ideas on behavior in the service of the internal milieu maintain their currency, and the search for the molecular bases for these relationships should serve as a research focus.

History, 20th Century↗

PubMed1990

Evolution at HLA: possible explanations for the deficiency of homozygotes in two populations.

There is substantial evidence that some form of balancing selection is important for loci in the HLA region. Two classic studies found a large deficiency of homozygotes for these loci. Four possible proposed selective explanations were proposed: (1) heterozygous advantage; (2) linked lethal; (3) maternal-fetal interaction, and (4) resistance to infectious disease. These hypotheses as well as another explanation, different male and female gametic frequencies, have been examined here to try and evaluate their potential impact on genotypic frequencies. For any of these selective mechanisms to alone account for the observed homozygous deficiency, selection and/or others factors would have to be extremely strong. The linked lethal selection model and the hypothesis based on different male and female gametic frequencies appear to be unlikely explanations for these observations. Other factors that may influence genotypic frequencies are also discussed.

Female↗

PubMed2006

Building of an experimental cline with Arabidopsis thaliana to estimate herbicide fitness cost.

Various management strategies aim at maintaining pesticide resistance frequency under a threshold value by taking advantage of the benefit of the fitness penalty (the cost) expressed by the resistance allele outside the treated area or during the pesticide selection "off years." One method to estimate a fitness cost is to analyze the resistance allele frequency along transects across treated and untreated areas. On the basis of the shape of the cline, this method gives the relative contributions of both gene flow and the fitness difference between genotypes in the treated and untreated areas. Taking advantage of the properties of such migration-selection balance, an artificial cline was built up to optimize the conditions where the fitness cost of two herbicide-resistant mutants (acetolactate synthase and auxin-induced target genes) in the model species Arabidopsis thaliana could be more accurately measured. The analysis of the microevolutionary dynamics in these experimental populations indicated mean fitness costs of approximately 15 and 92% for the csr1-1 and axr2-1 resistances, respectively. In addition, negative frequency dependence for the fitness cost was also detected for the axr2-1 resistance. The advantages and disadvantages of the cline approach are discussed in regard to other methods of cost estimation. This comparison highlights the powerful ability of an experimental cline to measure low fitness costs and detect sensibility to frequency-dependent variations.

Alleles↗

PubMed2005

Survival analysis of life span quantitative trait loci in Drosophila melanogaster.

We used quantitative trait loci (QTL) mapping to evaluate the age specificity of naturally segregating alleles affecting life span. Estimates of age-specific mortality rates were obtained from observing 51,778 mated males and females from a panel of 144 recombinant inbred lines (RILs). Twenty-five QTL were found, having 80 significant effects on life span and weekly mortality rates. Generation of RILs from heterozygous parents enabled us to contrast effects of QTL alleles with the means of RIL populations. Most of the low-frequency alleles increased mortality, especially at younger ages. Two QTL had negatively correlated effects on mortality at different ages, while the remainder were positively correlated. Chromosomal positions of QTL were roughly concordant with estimates from other mapping populations. Our findings are broadly consistent with a mix of transient deleterious mutations and a few polymorphisms maintained by balancing selection, which together contribute to standing genetic variation in life span.

Alleles↗

PubMed2006

Unique evolutionary mechanism in R-genes under the presence/absence polymorphism in Arabidopsis thaliana.

While the presence/absence polymorphism is commonly observed in disease resistance (R-) genes in Arabidopsis, only a few R-genes under the presence/absence polymorphism (R-P/A) have been investigated. To understand the mechanism of the molecular evolution of R-P/A, we investigated genetic variation of nine R-P/A in A. thaliana from worldwide populations. The number of possessed R-genes varied widely among accessions (two to nine, on average 4.3 +/- 1.6/accession). No pair of accessions shared the same haplotype, and no clear geographic differentiation was observed with respect to the pattern of presence/absence of the R-genes investigated. Presence allele frequencies also varied among loci (25-70%), and no linkage disequilibrium was detected among them. Although the LRR region in regular R-genes is known to be highly polymorphic and has a high Ka/Ks ratio in A. thaliana, nucleotide sequences of this region in the R-P/A showed a relatively low level of genetic variation (pi = 0.0002-0.016) and low Ka/Ks (0.03-0.70, <1). In contrast, the nucleotide diversities around the deletion junction of R-P/A were constantly high between presence and absence accessions for the R-genes (D(xy) = 0.031-0.103). Our results suggest that R-P/A loci evolved differently from other R-gene loci and that balancing selection plays an important role in molecular evolution of R-P/A.

Alleles↗

PubMed2005

The concordance of gene trees and species trees at two linked loci.

The gene genealogies of two linked loci in three species are analyzed using a series of Markov chain models. We calculate the probability that the gene tree of one locus is concordant with the species tree, given that the gene tree of the other locus is concordant. We define a threshold value of the recombination rate, r*, to be the rate for which the difference between the conditional probability of concordance and its asymptotic value is reduced to 5% of the initial difference. We find that, although r* depends in a complicated way on the times of speciation and effective population sizes, it is always relatively small, <10/N4, where N4 is the effective size of the species represented by the internal branch of the species tree. Consequently, the concordance of gene trees of neutral loci with the species tree is expected to be on roughly the same length scale on the chromosome as the extent of significant linkage disequilibrium within species unless the effective size of contemporary populations is very different from the effective sizes of their ancestral populations. Both balancing selection and selective sweeps can result in much longer genomic regions having concordant gene trees.

Animals↗

PubMed2006

Nonallelic interactions between het-c and a polymorphic locus, pin-c, are essential for nonself recognition and programmed cell death in Neurospora crassa.

Nonself recognition in filamentous fungi is conferred by genetic differences at het (heterokaryon incompatibility) loci. When individuals that differ in het specificity undergo hyphal fusion, the heterokaryon undergoes a programmed cell death reaction or is highly unstable. In Neurospora crassa, three allelic specificities at the het-c locus are conferred by a highly polymorphic domain. This domain shows trans-species polymorphisms indicative of balancing selection, consistent with the role of het loci in nonself recognition. We determined that a locus closely linked to het-c, called pin-c (partner for incompatibility with het-c) was required for het-c nonself recognition and heterokaryon incompatibility (HI). The pin-c alleles in isolates that differ in het-c specificity were extremely polymorphic. Heterokaryon and transformation tests showed that nonself recognition was mediated by synergistic nonallelic interactions between het-c and pin-c, while allelic interactions at het-c increased the severity of the HI phenotype. The pin-c locus encodes a protein containing a HET domain; predicted proteins containing HET domains are frequent in filamentous ascomycete genomes. These data suggest that nonallelic interactions may be important in nonself recognition in filamentous fungi and that proteins containing a HET domain may be a key factor in these interactions.

Alleles↗

PubMed2006

The role of HLA promoters in autoimmunity.

Population studies reveal HLA class I and class II gene polymorphisms associated with all the common chronic autoimmune diseases, notably spondylarthropathies, rheumatoid arthritis, multiple sclerosis and type I diabetes. We here discuss the exceptionally high levels of nucleotide diversity in the MHC region likely to reflect not only balancing selection acting on the epitope binding sites but also natural selection operating on the promoter region. The latter possibility is supported by functional studies with promoters, higher levels of diversity in the promoters of class II than class I genes and the relatively high frequency of single nucleotide polymorphisms around transcription factor binding sites. This, we argue, reflects the need for an appropriate level of signalling at the immunological synapse. We here summarise our knowledge of HLA promoter polymorphisms and how these translate into differential expression, T cell polarisation and inflammation. We discuss current strategies for pharmaceutical intervention in HLA expression.

Animals↗

PubMed2004

Allelic polymorphism in the ovine DQA1 gene.

Variation in the ovine DQA1 gene was investigated by amplification of exon 2 using PCR, followed by single-strand conformational polymorphism (SSCP) analysis, cloning, and DNA sequencing. Fourteen novel SSCP patterns, representing 14 different sequences, were identified. Eight of these 14 sequences were identical to published DQA1 sequences from sheep, whereas the remaining six were novel but similar to the published DQA1 sequences from sheep and cattle. These six new sequences exhibited conserved region and variable region patterns similar to the published sheep DQA1 sequences, but were different than the published DQA2 sequences from sheep. All of these 14 putative sheep DQA1 sequences fulfilled the criteria used by the established bovine leukocyte antigens major histocompatibility complex nomenclature committee for assignment as new alleles. Comparison of the available DQA1 sequences from sheep and cattle revealed several clusters of ovine DQA1 sequences, and some sheep alleles were more similar to cattle alleles than other sheep alleles. The occurrence of trans-species polymorphism suggests the action of balancing selection at the DQA1 locus. Twenty-four percent of the nucleotide positions showed variation within exon 2, and this variation seems to have arisen largely by point mutation and gene conversion. The nonsynonymous and synonymous substitution rates were similar in both the putative antigen-binding site codons and the putative nonantigen-binding site codons. The extensive polymorphism reported in this article is consistent with polymorphism reported at the bovine DQA1 locus.

Alleles↗

PubMed2000

A pharmaceutical needs assessment in a primary care setting.

BACKGROUND: As part of a reconfiguration of its general medical services, Ardach Health Centre has integrated a community pharmacist into the centre to provide pharmaceutical care. In order to systematically identify areas of 'pharmaceutical need', a needs assessment was carried out during October 1997. AIM: To prioritize and assist the planning of pharmaceutical care provision within the centre, such that maximum gain could be achieved from inevitable limited resources. METHOD: A four-stage pharmaceutical needs assessment method was created around a selection of techniques: gap analysis, the nominal group technique, and rapid participatory appraisal. This was then applied to a random sample of people drawn from the patient register of Ardach Health Centre and all the health care professionals associated with their care. RESULTS: Through the four-stage process, a pharmaceutical service priority league table was constructed to reflect the unmet pharmaceutical needs of patients and their primary health care providers. The table provided a structured framework around which pharmaceutical service provision within the health centre could be planned. CONCLUSION: We have developed a pragmatic, systematic method of identifying the prevalence of unmet pharmaceutical needs of a community. The assessment assisted service selection, balancing what should be done with what could be done and what could be afforded.

Data Collection↗

PubMed2002

Identification of potentially effective antisense oligodeoxyribonucleotide (ODN) sequences for inhibiting plasminogen activator inhibitor-2 (PAI-2) production by monocytes.

OBJECTIVE: Monocyte fibrinolytic activity may influence thrombus resolution. The balance between uPA and PAI-2 could determine the fibrinolytic activity of the monocyte. Inhibiting PAI-2 production using specific antisense sequences might alter this balance. Selecting effective sequences is a problem as prediction of the secondary structure of target mRNA is difficult. This study reports the modification of a cell free system for rapid antisense screening. METHODS: Five 18-19 mer oligodeoxynucleotides (ODN), sequences A, B, K, T and Q, and their matched scrambled controls were designed and screened using a modified rabbit reticulocyte lysate transcription and translation system (RRL). Intracellular uptake of ODNs was confirmed by fluorescence microscopy, scanning laser confocal microscopy and fluorimetry. Monocytes were transfected with a liposome/ODN complex using sequences A, B, A + B combined, or T and PAI-2 levels measured by ELISA. Inhibition of PAI-2 production was calculated as a percentage of control levels (baseline and scrambled). RESULTS: (i) RRL System--Sequence A was the most effective inhibitor of PAI-2 production in this system (median 63%) compared with sequences, B median 9%, K median 14%, T median 11% and Q median -8% respectively (n = 3). Sequence A was the only sequence, which always inhibited PAI-2. This was confirmed using fluorescently labelled protein (n = 2). (ii) Monocyte transfection--Fluorescence microscopy and fluorimetry showed that intracellular delivery of labelled antisense was only achieved when a liposome was used. Transfection of monocytes extracted from 5 subjects showed that sequence A significantly reduced PAI-2 production (mean % 41.4, sem 9.1) compared with sequences B (mean% 3.4, sem 8.9, p = 0.04), A + B (mean % 0.4, sem 7.8, p = 0.04), and T (mean % 5.4, sem 4.9, p = 0.01). Further studies using sequence A on cells from 10 subjects showed a significant reduction in monocyte PAI-2 production (27.6 ng/ml, sem 3.9) compared with matched scrambled controls (mean 38.3 ng/ml, sem 4.5, p = 0.0112) and baseline (mean 51.4 ng/ml, sem 6.7, p = 0.0009). CONCLUSION: Use of the RRL screening system allowed the selection of a novel antisense sequence, which significantly reduced PAI-2 production in monocytes.

Cell-Free System↗