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Results for “balancing selection”

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PubMed2006

Restrictive flamenco alleles are maintained in Drosophila melanogaster population cages, despite the absence of their endogenous gypsy retroviral targets.

The flamenco (flam) locus, located at 20A1-3 in the centromeric heterochromatin of the Drosophila melanogaster X chromosome, is a major regulator of the gypsy/mdg4 endogenous retrovirus. In restrictive strains, functional flam alleles maintain gypsy proviruses in a repressed state. By contrast, in permissive strains, proviral amplification results from infection of the female germ line and subsequent insertions into the chromosomes of the progeny. A restrictive/permissive polymorphism prevails in natural and laboratory populations. This polymorphism was assumed to be maintained by the interplay of opposite selective forces; on one hand, the increase of genetic load caused by proviral insertions would favor restrictive flam alleles because they make flies resistant to these gypsy replicative transpositions and, on the other, a hypothetical resistance cost would select against such alleles in the absence of the retrovirus. However, the population cage data presented in this paper do not fit with this simple resistance cost hypothesis because restrictive alleles were not eliminated in the absence of functional gypsy proviruses; on the contrary, using 2 independent flam allelic pairs, the restrictive frequency rose to about 90% in every experimental population, whatever the pair of alleles and the allelic proportions in the initial inoculum. These data suggest that the flam polymorphism is maintained by some strong balancing selection, which would act either on flam itself, independently of the deleterious effect of gypsy, or on a hypothetical flanking gene, in linkage disequilibrium with flam. Alternatively, restrictive flam alleles might also be resistant to some other retroelements that would be still present in the cage populations, causing a positive selection for these alleles. Whatever selective forces that maintain high levels of restrictive alleles independently of gypsy, this unknown mechanism can set up an interesting kind of antiviral innate immunity, at the population level.

Alleles↗

PubMed2004

Allelic polymorphism of TCRalpha chain constant domain genes in the bicolor damselfish.

T cell receptor (TCR) chains are composed of two extracellular domains, the membrane-distal variable domain and the membrane-proximal constant domain. Data presented here show that the TCRA 'constant' (C) domain of damselfish exhibits considerable allelic polymorphisms that appear to be positively selected. Each of 32 damselfish TCRAC clones showed different patterns of atypical polymorphism in the constant region. Twenty-three of the 121 TCRalpha constant region amino acid residues show substitutions, clustered mainly in the loops between the beta strands. Coding regions of the TCRAC genes differ by up to 8% at the nucleotide level and 20% at the amino acid level. Southern hybridization, polymorphism segregation, and genomic cloning data suggest allelic polymorphism at two TCRAC genes, distinguished by a single amino acid. KA/KS ratios suggest that balancing selection is acting to maintain polymorphisms at the variable sites of one of these genes, but not the other, in a manner comparable to the peptide binding regions of MHC. Nonetheless, each TCRAC gene is spliced to variable and joining segments similar to those described in other species. These data suggest that our understanding of the function of the TCR constant domains of these vertebrates is incomplete.

Alleles↗

PubMed2003

On the evolutionary advantage of fitness-associated recombination.

The adaptive value of recombination remains something of a puzzle. One of the basic problems is that recombination not only creates new and advantageous genetic combinations, but also breaks down existing good ones. A negative correlation between the fitness of an individual and its recombination rate would result in prolonged integrity of fitter genetic combinations while enabling less fit ones to produce new combinations. Such a correlation could be mediated by various factors, including stress responses, age, or direct DNA damage. For haploid population models, we show that an allele for such fitness-associated recombination (FAR) can spread both in asexual populations and in populations reproducing sexually at any uniform recombination rate. FAR also carries an advantage for the population as a whole, resulting in a higher average fitness at mutation-selection balance. These results are demonstrated in populations adapting to new environments as well as in well-adapted populations coping with deleterious mutations. Current experimental results providing evidence for the existence of FAR in nature are discussed.

Adaptation, Physiological↗

PubMed2006

A comparison of variability and population structure for major histocompatibility complex and microsatellite loci in California coastal steelhead (Oncorhynchus mykiss Walbaum).

The major histocompatibility complex (MHC) contains genes integral to immune response in vertebrates. MHC genes have been shown to be under selection in a number of vertebrate taxa, making them intriguing for population genetic studies. We have conducted a survey of genetic variation in an MHC class II gene for steelhead trout from 24 sites in coastal California and compared this variation to that observed at 16 presumably neutral microsatellite loci. A high amount of allelic variation was observed at the MHC when compared to previously published studies on other Pacific salmonids. Elevated nonsynonymous substitutions, relative to synonymous substitutions, were detected at the MHC gene, indicating the signature of historical balancing selection. The MHC data were tested for correlations to and deviations from the patterns found with the microsatellite data. Estimates of allelic richness for the MHC gene and for the microsatellites were positively correlated, as were estimates of population differentiation (F(ST)). An analysis for F(ST) outliers indicates that the MHC locus has an elevated F(ST) relative to the neutral expectation, although a significant result was found for only one particular geographical subgroup. Relatively uniform allele frequency distributions were detected in four populations, although this finding may be partially due to recent population bottlenecks. These results indicate that, at the scale studied here, drift and migration play a major role in the observed geographical variability of MHC genes in steelhead, and that contemporary selection is relatively weak and difficult to detect.

Alleles↗

PubMed2002

Genetic polymorphism at two linked loci, Sod and Est-6, in Drosophila melanogaster.

We have examined the patterns of polymorphism at two linked loci, Sod and Est-6, separated by nearly 1000 kb on the left arm of chromosome 3 of Drosophila melanogaster. The evidence suggests that natural selection has been involved in shaping the polymorphisms. At the Sod locus, a fairly strong (s>0.01) selective sweep, started >or=2600 years ago, increased the frequency of a rare haplotype, F(A), to about 50% frequency in populations of Europe, Asia, and the Americas. More recently, an F(A) allele mutated to an S allele, which has increased to frequencies 5-15% in populations of Europe, Asia and North America. All S alleles are identical (or very nearly) in sequence and differ by one nucleotide substitution (which accounts for the F-->S electrophoretic difference) from F(A) alleles. At the Est-6 locus, the evidence indicates both directional and balancing selection impacting separately the promoter and the coding regions of the gene, with linkage disequilibrium occurring within each region. Some linkage disequilibrium also exists between the two genes.

Alleles↗

PubMed1997

Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population.

Selection is usually considered to be the dominant force controlling viral variation; the large population sizes suggest that deterministic population genetic models are appropriate. To investigate their validity for HIV, samples of env gene sequences were tested for departure from neutrality because of mutation-selection balance. None of the samples departed significantly when tested as nucleotide sequences. At the amino acid level, significantly elevated diversity was detected in two samples within, but not outside, the V3 loop. The effective population number has been estimated (using a phylogenetic method) to be close to 10(3). Estimates from nucleotide diversity are about 2-fold lower. The low value of the effective population number might arise from high variability in progeny number between infected cells, from the expansion in population number from a small inoculum as the virus is transmitted between hosts, or from variable selection at linked sites. These results suggest that the population genetics of HIV are best described by stochastic models.

Amino Acid Sequence↗

PubMed1987

Genetic differentiation of quantitative characters between populations or species. II: Optimal selection in infinite populations.

Using a new and more general genetic model called the discrete-allelic state model and assuming discrete-time process, the evolutionary changes of genetic variation of quantitative characters, controlled by a few loci, within and between populations during the process of genetic differentiation of populations or species, are studied under the effects of mutation and centripetal selection in infinitely large populations. While in a finite population and ignoring selection, the rate of change of additive genetic variance depends on mutation and effective population size, traits under optimal selection in infinitely large populations go through the dynamics of a rather complicated form depending on the relative intensities of selection and mutation. When a population, which has reached steady-state by mutation-selection balance, splits into two, in one of which the same optimum genotype holds but in the other the optimum shifts a few standard deviations away from the original optimum, the corresponding daughter population starts differentiating from its sister population by favouring certain class of mutant alleles and discarding others which were originally favoured. During this process of turn over of genes, both the intra- and inter-populational variances undergo a complicated change, and the ratio of the former to the latter is a non-linear function of time of divergence. This pattern is qualitatively very different from the case when selection is absent. The intra-population distribution of genotypic values, during this transition, is shown to deviate considerably from normality. The presence of linkage seems to retard the accumulation of intra-populational genetic variance. The implications of these results are discussed in comparison with the earlier findings of evolutionary models of quantitative traits.

Alleles↗

PubMed1974

Selection by fertility in Drosophila pseudoobscura.

Fertility, the component of selection due to female fecundity and male mating success, differed significantly among the ST/ST, ST/AR, and AR/AR karyotypes in experimental populations and varied with karyotypic frequency. In relation to ST/AR, ST/ST females and males had higher fertilities at low frequency; AR/AR males and females were at a significant fertility disadvantage at intermediate frequency, while at low and at high frequencies their fertilities matched or exceeded that of the heterokaryotype. These fertility differences were comparable in size to viability differences previously reported for D. pseudoobscura karyotypes. Differential fertility seems likely to be an important element, perhaps just as important as differential viability, in the balancing selection that maintains the chromosomal polymorphism in this species.

Animals↗

PubMed1993

Predictions of the dynamics of a polygenic character under directional selection.

A quantitative genetic model for the response of the distribution of a single metric trait to directional selection is investigated. Particular attention is paid to the performance of approximations that use only limited information on the initial state of the population, such as the mean, the variance, the skewness and the kurtosis. Selection is imposed according to an exponentially increasing fitness function, populations mate at random, have discrete generations, and all genetic effects are supposed to be additive. Neglecting random drift, qualitatively different predictions for the initial response of a large population that has previously been at a mutation-stabilizing selection balance are derived. These depend on different assumptions about the initial distribution and are compared to the exact dynamics of that model. Linkage disequilibrium can be ignored as long as linkage is not too tight. The mathematical analysis rests on the method of cumulants and of cumulant-generating functions and produces exact equations for the evolution of cumulants in this model. Small populations subject to random drift are shown to respond in a qualitatively different way. The case of small populations is treated, primarily, by Monte Carlo simulations. The consequences of qualitatively different assumptions about maintenance of variation through mutation for the initial response to exponential directional selection are discussed. It is concluded that a significant initial increase in variance is unlikely to be observed in selection experiments if the effective population size is not larger than 500 and if response is caused by additive genes. The present results also apply to weak truncation selection.

Mathematics↗

PubMed2004

Variation after a selective sweep in a subdivided population.

The effect of genetic hitchhiking on neutral variation is analyzed in subdivided populations with differentiated demes. After fixation of a favorable mutation, the consequences on particular subpopulations can be radically different. In the subpopulation where the mutation first appeared by mutation, variation at linked neutral loci is expected to be reduced, as predicted by the classical theory. However, the effect in the other subpopulations, where the mutation is introduced by migration, can be the opposite. This effect depends on the level of genetic differentiation of the subpopulations, the selective advantage of the mutation, the recombination frequency, and the population size, as stated by analytical derivations and computer simulations. The characteristic outcomes of the effect are three. First, the genomic region of reduced variation around the selected locus is smaller than that predicted in a panmictic population. Second, for more distant neutral loci, the amount of variation increases over the level they had before the hitchhiking event. Third, for these loci, the spectrum of gene frequencies is dominated by an excess of alleles at intermediate frequencies when compared with the neutral theory. At these loci, hitchhiking works like a system that takes variation from the between-subpopulation component and introduces it into the subpopulations. The mechanism can also operate in other systems in which the genetic variation is distributed in clusters with limited exchange of variation, such as chromosome arrangements or genomic regions closely linked to targets of balancing selection.

Animals↗

PubMed1999

Polymorphism and transcription of Mhc class I genes in a passerine bird, the great reed warbler.

The class I genes of the major histocompatibility complex (Mhc) are here investigated for the first time in a passerine bird. The great reed warbler is a rare species in Sweden with a few semi-isolated populations. Yet, we found extensive Mhc class I variation in the study population. The variable exon 3, corresponding to the alpha2 domain, was amplified from genomic DNA with degenerated primers. Seven different genomic class I sequences were detected in a single individual. One of the sequences had a deletion leading to a shift in the reading frame, indicating that it was not a functional gene. A randomly selected clone was used as a probe for restriction fragment length polymorphism (RFLP) studies in combination with the restriction enzyme Pvu II. The RFLP pattern was complex with 21-25 RFLP fragments per individual and extensive variation. Forty-nine RFLP genotypes were detected in 55 tested individuals. To study the number of transcribed genes, we isolated 14 Mhc class I clones from a cDNA library from a single individual. We found eight different sequences of four different lengths (1.3-2.2 kilobases), suggesting there are at least four transcribed loci. The number of nonsynonymous substitutions (dN) in the peptide binding region of exon 3 were higher than the number of synonymous substitutions (dS), indicating balancing selection in this region. The number of transcribed genes and the numerous RFLP fragments found so far suggest that the great reed warbler does not have a "minimal essential Mhc" as has been suggested for the chicken.

3' Untranslated Regions↗

PubMed2001

African diversity from the HLA point of view: influence of genetic drift, geography, linguistics, and natural selection.

This study investigates the influence of different evolutionary factors on the patterns of human leukocyte antigen (HLA) genetic diversity within sub-Saharan Africa, and between Africa, Europe, and East Asia. This is done by comparing the significance of several statistics computed on equivalent population data sets tested for two HLA class II loci, DRB1 and DPB1, which strongly differ from each other by the shape of their allelic distributions. Similar results are found for the two loci concerning highly significant correlations between geographic and genetic distances at the world scale, high levels of genetic diversity within sub-Saharan Africa and East Asia, and low within Europe, and low genetic differentiations among the three broad continental areas, with no special divergence of Africa. On the other hand, DPB1 behaves as a neutral polymorphism, although a significant excess of heterozygotes is often observed for DRB1. Whereas the pattern observed for DPB1 is explained by geographic differentiations and genetic drift in isolated populations, balancing selection is likely to have prevented genetic differentiations among populations at the DRB1 locus. However, this selective effect did not disrupt the high correlation found between DRB1 and geography at the world scale, nor between DRB1 and linguistic differentiations at the African level.

Africa South of the Sahara↗

PubMed2006

Selective trade-offs and sex-chromosome evolution in Silene latifolia.

Alleles of sexually antagonistic genes (i.e., genes with alleles affecting fitness in opposite directions in the two sexes) can avoid expression in the sex to which they are detrimental via two processes: they are subsumed into the nonrecombining, sex-determining portion of the sex chromosomes or they evolve sex-limited expression. The former is considered more likely and leads to Y-chromosome degeneration. We mapped quantitative trait loci of major effect for sexually dimorphic traits of Silene latifolia to the recombining portions of the sex chromosomes and found them to exhibit sex-specific expression, with the Y chromosome in males controlling a relatively larger proportion of genetic variance than the X in females and the average autosome. Both reproductive and ecophysiological traits map to the recombining region of the sex chromosomes. We argue that genetic correlations among traits maintain recombination and polymorphism for these genes because of balancing selection in males, whereas sex-limited expression represses detrimental alleles in females. Our data suggest that the Y chromosome of S. latifolia plays a major role in the control of key metabolic activities beyond reproductive functions.

Alleles↗

PubMed2004

Distribution of genetic variation in the growth hormone 1 gene in Atlantic salmon (Salmo salar) populations from Europe and North America.

The level and hierarchical distribution of genetic variation in complete sequences of the Atlantic salmon (Salmo salar) growth hormone (GH1) gene were investigated in populations from Europe and North America with a view to inferring the major evolutionary forces affecting genetic variation at this locus. Seventeen polymorphic sites were identified in complete sequences from nine populations, with levels of noncoding (intron and untranslated region sequences) nucleotide diversity being similar to those observed in other species. No variation, however, was observed in exonic sequences, indicating that nucleotide diversity in the Atlantic salmon GH1 gene is three and 25 times less than that estimated for human and Drosophila coding sequences, respectively. This suggests that purifying selection is the predominant contemporary force controlling the molecular evolution of GH1 coding sequences. Comparison of haplotype relationships within and between populations indicated that differentiation between populations from Europe and North America was greater than within-continent comparisons. However, several haplotypes observed in the northernmost European populations were more similar to those observed in North American than to any other haplotypes observed in Europe. This is most likely to be a result of historical, rather than contemporary, gene flow. Neutrality test statistics, such as Tajima's D, were significantly positive in the European populations in which North American-like haplotypes were observed. Although a positive Tajima's D is commonly interpreted as the signal of balancing selection, a more likely explanation in this case is that either historical migration or ascertainment bias, rather than within population local adaptation, has given rise to an excess of intermediate frequency alleles.

Amino Acid Sequence↗

PubMed1997

A microsatellite-based MHC genotyping system for house mice (Mus domesticus).

Major histocompatibility complex (MHC) genes are the most polymorphic loci known for vertebrates. Although this has been known for over two decades, the selective forces maintaining this genetic diversity are unclear. Efforts to study selection on these loci in nature have been hampered because no simple MHC typing systems are available. Here, we describe and evaluate a microsatellite-based MHC genotyping system for house mice (Mus domesticus). Thirty-five MHC-linked microsatellite loci were tested for amplification and scoring reliability, and 21 were deemed useful. These 21 loci were efficient at discriminating among nine serologically distinct MHC haplotypes, with 52% of microsatellite pairs providing 100% resolution. Since these microsatellite loci are scattered across the entire MHC region, they will be effective at detecting recombinant haplotypes. The number of alleles is higher for microsatellites inside the MHC than outside it, which presumably reflects genetic hitchhiking with MHC alleles under balancing selection. This microsatellite typing system now allows testing hypotheses about the nature of selection operating on MHC genes in natural populations of M. domesticus and other murid rodent species.

Alleles↗

PubMed2005

MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the Southern Kalahari.

Major histocompatibility complex (MHC) variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or frequency-dependent selection. However, empirical support for these hypotheses under natural conditions is rare. In this study, we investigated the genetic constitution of the functionally important MHC class II gene (DRB exon 2) and the parasite load in a population of the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Fifty-eight individuals were genetically examined and the endoparasite load was quantified by counting fecal helminth eggs by using a modified McMaster technique. Thirty-four animals (58.6%) were infected. We identified 20 different MHC alleles with high levels of sequence divergence between alleles. Particularly, the antigen-binding sites revealed a significant higher rate of nonsynonymous substitutions (d(N)) than synonymous substitutions (d(S)), giving strong evidence of balancing selection. Heterozygosity did influence the infection status (being infected or not) and the individual fecal egg count (FEC) value with significantly higher values observed in homozygous individuals. Furthermore, a positive relationship was found between specific alleles and parasite load. The allele Rhpu-DRB*1 significantly occurred more frequently in infected individuals and in individuals with high FEC values (high parasite load). Individuals with the allele Rhpu-DRB*1 had a 1.5-fold higher chance of being infected than individuals without this allele (odds ratio test, P < 0.05). Contrarily, the allele Rhpu-DRB*8 significantly occurred more frequent in individuals with low FEC values. Our results support the hypotheses that MHC polymorphism in R. pumilio is maintained through pathogen-driven selection acting by both heterozygosity advantage and frequency-dependent selection.

Animals↗

PubMed2006

Contrasting signatures of selection on the Plasmodium falciparum erythrocyte binding antigen gene family.

Erythrocyte binding antigens of Plasmodium falciparum are involved in erythrocyte invasion, and may be targets of acquired immunity. Of the five eba genes, protein products have been detected for eba-175, eba-181 and eba-140, but not for psieba-165 or ebl-1, providing opportunity for comparative analysis of genetic variation to identify selection. Region II of each of these genes was sequenced from a cross-sectional sample of parasites in an endemic Kenyan population, and the frequency distributions of polymorphisms analysed. A positive value of Tajima's D was observed for eba-175 (D=1.13) indicating an excess of intermediate frequency polymorphisms, while all other genes had negative values, the most negative being ebl-1 (D=-2.35) followed by psieba-165 (D=-1.79). The eba-175 and ebl-1 genes were then studied in a sample of parasites from Thailand, for which a positive Tajima's D value was again observed for eba-175 (D=1.79), and a negative value for ebl-1 (D=-1.85). This indicates that eba-175 is under balancing selection in each population, in strong contrast to the other members of the gene family, particularly ebl-1 and psieba-165 that may have been under recent directional selection. Population expansion simulations were performed under a neutral model, further supporting the departures from neutrality of these genes.

Animals↗

PubMed1997

The evolution of genomic imprinting: two modifier-locus models.

We present two autosomal two-locus models in which the primary locus, A, may be imprinted according to the alleles present at the second, modifier locus, M. In the first model, the modifier is cis-acting, which assumes that imprinting occurs late in gametogenesis: whether or not A is imprinted depends only on the M allele in the (unfertilized) egg. We examine three cases in which polymorphism at A is maintained by a mutation-selection balance or heterozygote advantage. We show that a newly arising modifier allele without direct fitness effects can increase at a rate only of the order of the mutation rate at the A locus. This result mirrors that found in two-locus models of the evolution of dominance modifiers. Modifiers that also alter fitnesses, however, may spread quickly. In the second model, a monomorphic primary locus, A, is imprinted according to the mother's genotype at the second, diallelic modifier locus, M. The model is therefore trans-acting, which assumes imprinting occurs early in gametogenesis: whether or not A is imprinted depends on both of the mother's M genes. We show that a newly arising modifier will increase in frequency via selection if either imprinting is advantageous and the modifier increases the proportion of imprinted gametes or imprinting is disadvantageous and the proportion is decreased. Both of these factors-the selective effect of imprinting and the proportion of gametes imprinted-affect the rate of modifier evolution. Selectively maintained polymorphism at the modifier locus is unlikely unless the alleles interact in a nonadditive fashion.

Biological Evolution↗