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 487 records · Page 27Linked to original sources

PubMed2003

Large discrepancies in differentiation of allozymes, nuclear and mitochondrial DNA loci in recently founded Pacific populations of the pearl oyster Pinctada margaritifera.

This study presents a comparative analysis of population structure applied to the pearl oyster (Pinctada margaritifera) from the Central Pacific islands using three classes of molecular markers: two mitochondrial genes (mtDNA), five anonymous nuclear loci (anDNA), and eight polymorphic allozymes. Very low levels of haplotype diversity and nucleotidic divergence detected for mtDNA validate the hypothesis of a recent (re)colonization of Polynesian lagoons after their exondation during the last glaciations. Some nuclear loci, however, showed highly significant FST values, indicating a reduced amount of larval exchange between archipelagos at present. A large interlocus variance of FST was nevertheless observed. We discuss whether this pattern is inherent to the stochasticity of the drift process since recolonization, or if it could result from balancing selection acting on certain loci. This study illustrates once more the need to combine the analysis of several kinds of loci when unrelated phenomena are likely to leave their footprints on genetic structure.

Animals↗

PubMed1999

Locus and population specific evolution in HLA class II genes.

The population genetics of the HLA class II loci was studied with reference to variation in the frequency of (a) alleles at a locus and (b) amino acids at specific sites. Variation was surveyed at 4 loci (DRB1, DQA1, DQB1, and DPB1) in 22 populations from the Twelfth International Histocompatibility Workshop (Saint-Malo, 1996). Allele and amino acid variation was measured by computing heterozygosity and the effective number of alleles. Substantial variations in polymorphism were observed among the various populations and loci studied. In the majority of the populations, DRB1 has the highest heterozygosity and effective number of alleles. As previously shown, the Amerindian populations have lower levels of allelic diversity when compared to other populations. At the amino acid level, DRB1 antigen recognition sites (ARS) have the highest heterozygosities and effective number of alleles. For the other loci (DPB1, DQA1, and DQB1) for which there is no crystal structure and for which ARS sites were inferred from DRB1, non-ARS sites were often among the sites with highest levels of variation. It is possible that these putative non-ARS sites do play a role in antigen presentation. The homozygosity test for neutrality was applied to allele and amino acid data. Of the four HLA class II loci studied, only DPB1 failed to show evidence of balancing selection. DQB1 and DQA1 depart significantly from neutrality in the largest number of populations. Genetic distances between populations were computed based on frequency of alleles and amino acids at ARS sites.

Alleles↗

PubMed2004

Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing.

Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we compared the predicted genes from the two genomes with those from the previously sequenced B31 genome. The three genomes are closely related and are evolutionarily approximately equidistant ( approximately 0.5% pairwise nucleotide differences on the main chromosome). We used a Poisson model of nucleotide substitution to screen for genes with elevated levels of nucleotide polymorphisms. The three-way genome comparison allowed distinction between polymorphisms introduced by mutations and those introduced by recombination using the method of phylogenetic partitioning. Tests for recombination suggested that patches of high-density nucleotide polymorphisms on the chromosome and plasmids arise by DNA exchange. The role of recombination as the main mechanism driving B. burgdorferi diversification was confirmed by multilocus sequence typing of 18 clinical isolates at 18 polymorphic loci. A strong linkage between the multilocus sequence genotypes and the major alleles of outer-surface protein C (ospC) suggested that balancing selection at ospC is a dominant force maintaining B. burgdorferi diversity in local populations. We conclude that B. burgdorferi undergoes genome-wide genetic exchange, including plasmid transfers, and previous reports of its clonality are artifacts from the use of geographically and ecological isolated samples. Frequent recombination implies a potential for rapid adaptive evolution and a possible polygenic basis of B. burgdorferi pathogenicity.

Amino Acid Sequence↗

PubMed2006

Presence/absence polymorphism for alternative pathogenicity islands in Pseudomonas viridiflava, a pathogen of Arabidopsis.

The contribution of arms race dynamics to plant-pathogen coevolution has been called into question by the presence of balanced polymorphisms in resistance genes of Arabidopsis thaliana, but less is known about the pathogen side of the interaction. Here we investigate structural polymorphism in pathogenicity islands (PAIs) in Pseudomonas viridiflava, a prevalent bacterial pathogen of A. thaliana. PAIs encode the type III secretion system along with its effectors and are essential for pathogen recognition in plants. P. viridiflava harbors two structurally distinct and highly diverged PAI paralogs (T- and S-PAI) that are integrated in different chromosome locations in the P. viridiflava genome. Both PAIs are segregating as presence/absence polymorphisms such that only one PAI ([T-PAI, nablaS-PAI] and [nablaT-PAI, S-PAI]) is present in any individual cell. A worldwide population survey identified no isolate with neither or both PAI. T-PAI and S-PAI genotypes exhibit virulence differences and a host-specificity tradeoff. Orthologs of each PAI can be found in conserved syntenic locations in other Pseudomonas species, indicating vertical phylogenetic transmission in this genus. Molecular evolutionary analysis of PAI sequences also argues against "recent" horizontal transfer. Spikes in nucleotide divergence in flanking regions of PAI and nabla-PAI alleles suggest that the dual PAI polymorphism has been maintained in this species under some form of balancing selection. Virulence differences and host specificities are hypothesized to be responsible for the maintenance of the dual PAI system in this bacterial pathogen.

Arabidopsis↗

PubMed2002

Ancestral polymorphism and adaptive evolution in the trichothecene mycotoxin gene cluster of phytopathogenic Fusarium.

Filamentous fungi within the Fusarium graminearum species complex (Fg complex) are the primary etiological agents of Fusarium head blight (scab) of wheat and barley. Scab is an economically devastating plant disease that greatly limits grain yield and quality. In addition, scabby grain is often contaminated with trichothecene mycotoxins that act as virulence factors on some hosts, and pose a serious threat to animal health and food safety. Strain-specific differences in trichothecene metabolite profiles (chemotypes) are not well correlated with the Fg complex phylogeny based on genealogical concordance at six single-copy nuclear genes. To examine the basis for this discord between species and toxin evolution, a 19-kb region of the trichothecene gene cluster was sequenced in 39 strains chosen to represent the global genetic diversity of species in the Fg complex and four related species of Fusarium. Phylogenetic analyses demonstrated that polymorphism within these virulence-associated genes is transspecific and appears to have been maintained by balancing selection acting on chemotype differences that originated in the ancestor of this important group of plant pathogens. Chemotype-specific differences in selective constraint and evidence of adaptive evolution within trichothecene genes are also reported.

DNA, Fungal↗

PubMed2003

Evolutionary dynamics of an Arabidopsis insect resistance quantitative trait locus.

Glucosinolate profiles differ among Arabidopsis thaliana ecotypes, caused by the composition of alleles at several glucosinolate biosynthetic loci. One of these, GS-Elong, harbors a family of methylthioalkylmalate synthase (MAM) genes that determine the side chain length of aliphatic glucosinolate structures. Fine mapping reveals that GS-Elong constitutes an insect resistance quantitative trait locus, caused by variation in glucosinolate profiles conferred by polymorphism of MAM alleles in this region. A sequence survey of randomly chosen ecotypes indicates that GS-Elong is highly variable among A. thaliana ecotypes: indel polymorphisms are frequent, as well as gene conversion events between gene copies arranged in tandem. Furthermore, statistical methods of molecular population genetics suggest that one of the genes, MAM2, is subject to balancing selection. This may be caused by ecological tradeoffs, i.e., by contrasting physiological effects of glucosinolates on generalist vs. specialist insects.

Animals↗

PubMed1975

Statistical analyses of Drosophila and human protein polymorphisms.

By using the distribution function of allelic frequencies which was recently derived by Kimura and Ota for the model of stepwise production of neutral alleles, the observed protein polymorphisms of Drosophila and man are tested for fit to the theory of neutral protein variation. The observed and theoretical distributions of alleles agree quite well except for the excess of rare alleles in the actual distributions. In human polymorphisms, the alleles with frequencies less than 1% are more numerous than expected, whereas in Drosophila, those with frequencies less than 10% are more numerous. It is pointed out that these results support my thesis that mutational pressure rather than balancing selection is the main cause for the maintenance of protein polymorphisms.

Alleles↗

PubMed1979

Fixation of a deleterious allele at one of two "duplicate" loci by mutation pressure and random drift.

We consider a diploid population and assume two gene loci with two alleles each, A and a at one locus and B and b at the second locus. Mutation from wild-type alleles A and B to deleterious alleles a and b occurs with mutation rates va and vb, respectively. We assume that alleles are completely recessive and that only the double recessive genotype aabb shows a deleterious effect with relative fitness 1-epsilon. Then, it can be shown that if va greater than vb mutant a becomes fixed in the population by mutation pressure and a mutation-selection balance is ultimately attained with respect to the B/b locus alone. The main aim of this paper is to investigate the situation in which va = vb exactly. In this case a neutral equilibrium is attained and either locus can drift to fixation for the mutant allele. Diffusion models are developed to treat the stochastic process involved whereby the deleterious mutant eventually becomes fixed in one of the two duplicated loci by random sampling drift in finite populations. In particular, the equation for the average time until fixation of mutant a or b is derived, and this is solved numerically for some combinations of parameters 4Nev and 4Ne epsilon, where v is the mutation rate (va = vb = v) and Ne is the effective size of the population. Monte Carlo experiments have been performed (using a device termed "pseudo sampling variable") to supplement the numerical analysis.

Alleles↗

PubMed1987

Toward a theory for the evolution of cultural communication: coevolution of signal transmission and reception.

A haploid sexual two-locus model of gene-culture coevolution is examined, in which a dichotomous phenotype subject to natural selection is transmitted vertically with probabilities dependent on the chosen parent's genotype and phenotype and the offspring's genotype. Stability conditions for the genetically monomorphic corner equilibria are obtained. In a specialization of this general model, one locus controls the transmission and the other controls the reception of adaptive information. The corner and edge equilibria of this doubly coevolutionary model are fully analyzed, and conditions for transmission and reception to coevolve are derived in terms of the efficiency of vertical transmission, the selective advantage gained from possessing the information, the costs of transmission and reception, and the recombination fraction between the two loci. Possible applications of the model are to the evolution of semantic alarm calls in vervet monkeys and the phonetic aspects of human language. In a third model with diploid genetics, we consider the initial increase of cultural transmission from a mutation-selection balance in which the adaptive phenotype is the consequence of a dominant gene at one locus. A second gene controls the transmission of the phenotype in such a way that a new mutant at this second locus permits learning of the adaptive phenotype from a parent who has it. This new mutant cannot increase when rare.

Animal Communication↗

PubMed1991

Heterozygosity at individual amino acid sites: extremely high levels for HLA-A and -B genes.

The amino acid heterozygosities per site for HLA-A and -B loci are determined to be extremely high by combining population serotypic frequencies with amino acid sequences. For the 54 amino acid sites thought to have functional importance, the average heterozygosity per site is 0.301. Sixteen positions have heterozygosities greater than 0.5 at one or both loci and the frequencies of amino acids at a given position are very even, resulting in nearly the maximum heterozygosity possible. Furthermore, the high heterozygosity is concentrated in the peptide-interacting sites, whereas the sites that interact with the T-cell receptor have lower heterozygosity. Overall, these results indicate the importance of some form of balancing selection operating at HLA loci, maybe even at the individual amino acid level.

Alleles↗

PubMed1995

Low major histocompatibility complex class II diversity in European and North American moose.

Major histocompatibility complex (MHC) genes encode cell surface proteins whose function is to bind and present intracellularly processed peptides to T lymphocytes of the immune system. Extensive MHC diversity has been documented in many species and is maintained by some form of balancing selection. We report here that both European and North American populations of moose (Alces alces) exhibit very low levels of genetic diversity at an expressed MHC class II DRB locus. The observed polymorphism was restricted to six amino acid substitutions, all in the peptide binding site, and four of these were shared between continents. The data imply that the moose have lost MHC diversity in a population bottleneck, prior to the divergence of the Old and New World subspecies. Sequence analysis of mtDNA showed that the two subspecies diverged at least 100,000 years ago. Thus, viable moose populations with very restricted MHC diversity have been maintained for a long period of time. Both positive selection for polymorphism and intraexonic recombination have contributed to the generation of MHC diversity after the putative bottleneck.

Alleles↗

PubMed1995

Complete congruence between gene diversity estimates derived from genotypic data at enzyme and random amplified polymorphic DNA loci in black spruce.

Controversy still exists over the adaptive nature of variation of enzyme loci. In conifers, random amplified polymorphic DNAs (RAPDs) represent a class of marker loci that is unlikely to fall within or be strongly linked to coding DNA. We have compared the genetic diversity in natural populations of black spruce [Picea mariana (Mill.) B.S.P.] using genotypic data at allozyme loci and RAPD loci as well as phenotypic data from inferred RAPD fingerprints. The genotypic data for both allozymes and RAPDs were obtained from at least six haploid megagametophytes for each of 75 sexually mature individuals distributed in five populations. Heterozygosities and population fixation indices were in complete agreement between allozyme loci and RAPD loci. In black spruce, it is more likely that the similar levels of variation detected at both enzyme and RAPD loci are due to such evolutionary forces as migration and the mating system, rather than to balancing selection and overdominance. Furthermore, we show that biased estimates of expected heterozygosity and among-population differentiation are obtained when using allele frequencies derived from dominant RAPD phenotypes.

Alleles↗

PubMed1998

Persistence of neutral polymorphisms in Lake Victoria cichlid fish.

Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.

Actins↗

PubMed1998

Major histocompatibility complex variation associated with juvenile survival and parasite resistance in a large unmanaged ungulate population.

Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high levels of genetic diversity widely observed at the major histocompatibility complex (MHC) of vertebrate hosts are consistent with the hypothesis of parasite-driven balancing selection acting to maintain MHC genetic diversity. To date, however, empirical evidence in support of this hypothesis, especially from natural populations, has been lacking. A large unmanaged population of Soay sheep (Ovis aries L.) is used to investigate associations between MHC variation, juvenile survival, and parasite resistance. We show in an unmanaged, nonhuman population that allelic variation within the MHC is significantly associated with differences in both juvenile survival and resistance to intestinal nematodes. Certain MHC alleles are associated with low survivorship probabilities and high levels of parasitism or vice versa. We conclude that parasites are likely to play a major role in the maintenance of MHC diversity in this population.

Alleles↗

PubMed1999

Analysis of population structure of the chestnut blight fungus based on vegetative incompatibility genotypes.

Vegetative incompatibility is a self/nonself-recognition system in fungi that has often been used for describing phenotypic diversity in fungal populations. A common hypothesis is that vegetative incompatibility polymorphisms are maintained by balancing selection. However, understanding the evolutionary significance of vegetative incompatibility and the factors that maintain these polymorphisms has been limited by a lack of knowledge of the underlying genetics of vegetative compatibility (vc) types. Genotypes of 64 vc types, controlled by six unlinked vegetative incompatibility (vic) loci, have been identified in the chestnut blight fungus, Cryphonectria parasitica. By interpreting vc type survey data in terms of vic genotypes, we estimated vic-allele frequencies and analyzed the multilocus genetic structure of 13 populations in Europe and 3 populations in the U.S. European populations have less vc type diversity than the US populations because of a combination of lower vic-allele diversity and limited recombination. Genotypic diversity of 10 populations in Italy correlated to the abundance of sexual structures; however, significant deviations from random mating suggest that either sexual reproduction may not contribute many offspring in these populations or that vic genes (or vic genotypes) are under selection. Most vic-allele frequencies deviated from 0.5, the equilibrium frequency predicted under frequency-dependent selection, providing no evidence for selection acting on these loci.

Journal Article↗

PubMed2006

Molecular heterosis of prion protein beta-oligomers. A potential mechanism of human resistance to disease.

The gene encoding prion protein is polymorphic in human populations, with over 40% of native Europeans, for example, being heterozygous for the Met-129 and Val-129 alleles. The polymorphism affects both the incidence and the clinical presentation of a range of prion diseases, with heterozygotes generally showing the highest levels of resistance. It has been suggested that an earlier epidemic of prion diseases exerted balancing selection on the two alleles, and we have previously demonstrated that the two encoded proteins have potentially compensating tendencies to form amyloid and soluble beta-oligomers, respectively, in vitro. More strikingly, here we demonstrate that mixed oligomers, composed of both allelic forms, show an extreme sluggishness in converting to amyloid in comparison with oligomers homogenous for either allele. It may be that this example of molecular heterosis in vitro provides the basis for maintenance of the polymorphism in the population and that beta-oligomers represent a form of PrP sequestered from pathogenic amyloid formation in vivo.

Alleles↗

PubMedDate not supplied

Male and female correlations for taster (P.T.C.) phenotypes and rate of adolescent development.

Growth and development from infancy to age 18 years in tasters and non-tasters of phenylthiocarbamide (P.T.C.) were studied in 50 female and 44 male subjects. Taster girls reached all indices of maturation an average of 3.8 months earlier than non-taster girls. The reverse was true for boys, non-tasters maturing on average 6.2 months earlier than tasters. For both sexes, there was a significant correlation between an overall Maturity Index and P.T.C. sensitivity, positive for girls and negative for boys. Thirty-two of the females and 20 of the males could be classified according to P.T.C. genotype. For these, the onset, midpoint, and end of the pubertal growth spurt was estimated. Heterozygotes reached these points at times intermediate to homozygotes. Taster females preceded non-taster females and non-taster males preceded taster males by about 6 months. The finding of reversed associations between P.T.C. phenotype and maturation in males and females implies that factors underlying the P.T.C. polymorphism may not be confined to mediation through thyroid metabolism, but may also involve other complex pathways of the hypothalamic-pituitary-gonadal axis, particularly those of the sex hormones. The data were examined for evidence of whether or not the findings could be related to a means of maintaining the P.T.C. polymorphism. A significant negative assortative mating pattern was found. This accords with reports from the literature indicating personality differences between early and late maturers and a tendency for spouses to have similar personality characteristics. However, disassortative mating alone could not produce a stable equilibrium. A hypothesis for the maintenance of the P.T.C. polymorphism is developed on the assumption that the timing of puberty is related to reproductive fitness and subject to balancing selection. Heterozygotes for P.T.C. would be at an advantage because they have intermediate maturation times. In this small sample, P.T.C. heterozygotes were also found to produce more offspring than homozygotes.

Adolescent↗

PubMed1990

Surprisingly uneven distribution of the T cell receptor V beta repertoire in wild mice.

We have examined TCR V beta expression in a collection of wild mice. Many of the mice were homozygous for a large deletion at the V beta locus, and many animals also suppressed expression of several V betas using self superantigens. Expression of V beta 8.2 was unexpectedly suppressed by a self superantigen in some wild mice, which was due to the presence in these animals of a variant V beta 8.2 gene. The amino acid changes in this gene product suggest contact sites between V beta and the superantigen. Although all V betas are expressed within each wild mouse population, individual mice have a limited and variable V beta repertoire. The independent origin of multiple V beta deletions and the presence of polymorphic self superantigens suggest that this variation may be maintained by balancing selection.

Amino Acid Sequence↗