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Results for “balancing selection”

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At least 325 records · Page 18Linked to original sources

PubMed1999

Heterozygosity excess at the cattle DRB locus revealed by large scale genotyping of two closely linked microsatellites.

A method for MHC DRB typing in cattle based on two closely linked and highly polymorphic microsatellites is described. The two microsatellites DRBP1ms and DRB3ms are located in intron 2 of the corresponding DRB gene. The very strong linkage disequilibrium between the two loci made it possible to establish DRB microsatellite haplotypes. The typing results with this method on reference samples followed closely that obtained with RFLP and direct sequence analysis of DRB3 exon 2. The method is well suited for large scale genotyping and was successfully applied for typing more than 600 unrelated animals representing 23 breeds. The data were used to test whether the observed DRB allele frequency distributions were consistent with that expected for selectively neutral alleles in populations at mutation-drift equilibrium. A significant heterozygosity excess was detected and there was an obvious trend across breeds towards a more even allele frequency distribution than expected. The deviation may be due to balancing selection acting on the DRB locus or by recent population bottlenecks.

Alleles↗

PubMed2003

Effects of habitat fragmentation and changes of dispersal behaviour after a recent population decline on the genetic variability of noncoding and coding DNA of a monogamous Malagasy rodent.

While interactions among demography, behaviour and genetic structure are well-documented for neutral genetic markers, the role of these parameters and the effects of genetic drift and selection are considerably less well understood in functional genes, such as the major histocompatibility complex (MHC). In this study, the consequences of habitat fragmentation and the effects of a current population decline on noncoding (mitochondrial DNA) and two coding MHC loci (DQA, DRB) with different functional importance were investigated in the small remnant subdivided population of the endangered Malagasy giant jumping rat (Hypogeomys antimena). Both neutral and selective markers revealed a significant genetic differentiation between the two remnant subpopulations. The FST values were much lower in the MHC DQA and DRB genes than in the mitochondrial data. The MHC DRB loci display the effects of both balancing selection (high sequence diversity, four times higher nonsynonymous than synonymous substitutions in the functionally important antigen-binding site positions, twice the average heterozygosity of individual amino acids at the positions identified as part of the antigen-binding site (ABS) than those outside the ABS and nonselective forces including genetic drift. Simultaneously with a current population decline offspring reduced their dispersal distances. No substantial effects were detected within the first 6 years of reduced gene flow in either mitochondrial or MHC markers.

Animals↗

PubMed2006

The role of mitochondrial respiration in physiological and evolutionary adaptation.

Aerobic mitochondria serve as the power sources of eukaryotes by producing ATP through oxidative phosphorylation (OXPHOS). The enzymes involved in OXPHOS are multisubunit complexes encoded by both nuclear and mitochondrial DNA. Thus, regulation of respiration is necessarily a highly coordinated process that must organize production, assembly and function of mitochondria to meet an organism's energetic needs. Here I review the role of OXPHOS in metabolic adaptation and diversification of higher animals. On a physiological timescale, endocrine-initiated signaling pathways allow organisms to modulate respiratory enzyme concentration and function under changing environmental conditions. On an evolutionary timescale, mitochondrial enzymes are targets of natural selection, balancing cytonuclear coevolutionary constraints against physiological innovation. By synthesizing our knowledge of biochemistry, physiology and evolution of respiratory regulation, I propose that we can now explore questions at the interface of these fields, from molecular translation of environmental cues to selection on mitochondrial haplotype variation.

Adaptation, Physiological↗

PubMed1999

Age- and sex-distribution of the mutation load.

We investigate the age and sex distribution of genetic fitness under mutation-selection balance by means of simple one-locus two-allele models. We find that the extent of age and sex variation in the mutation load is very dependent on the average effect of new mutations. If the average heterozygote selective effect of new mutations is large, then age and sex differences may constitute a significant fraction of the total load, and be significant as compared to standing genetic variation. Whether the mutation load will increase or decrease with age depends on the age- and sex-specific effects of the new mutations, and on the rate of accumulation of mutations in the germ line as individuals age. We argue that the load will most likely increase with age in animals with continuous germ-cell division throughout life, and that this will occur even when mutations have unconditionally deleterious effects. We show that a male-biased mutation rate is likely to result in both a male-biased mutation load and a load that increases with male age.

Age Distribution↗

PubMed2004

Quantitative trait loci affecting dengue midgut infection barriers in an advanced intercross line of Aedes aegypti.

Quantitative trait loci (QTL) affecting the ability of the Aedes aegypti midgut to become infected with Dengue 2 virus (DEN2) were mapped in the F5 generation of an advanced intercross line (AIL). A strain of Ae. aegypti previously selected for DEN2 susceptibility was crossed to a new strain selected for refractoriness to midgut infection. In P1 and F1 parents and 147 F5 offspring, genotypes at forty-four cDNA loci were analysed. A new sex linked QTL and a second QTL on chromosome II with genotypes subject to balancing selection were detected that condition midgut susceptibility. Alleles at these QTL contributed additively in determining susceptibility and accounted for approximately 24% of the phenotypic variance. Markers associated with a midgut escape barrier were inconsistently supported.

Aedes↗

PubMed1999

Positive selection drives the evolution of the Acp29AB accessory gland protein in Drosophila.

Nucleotide sequence variation at the Acp29AB gene region has been surveyed in Drosophila melanogaster from Spain (12 lines), Ivory Coast (14 lines), and Malawi (13 lines) and in one line of D. simulans. The approximately 1.7-kb region studied encompasses the Acp29AB gene that codes for a male accessory gland protein and its flanking regions. Seventy-seven nucleotide and 8 length polymorphisms were detected. Nonsynonymous polymorphism was an order of magnitude lower than synonymous polymorphism, but still high relative to other non-sex-related genes. In D. melanogaster variation at this region revealed no major genetic differentiation between East and West African populations, while differentiation was highly significant between the European and the two African populations. Comparison of polymorphism and divergence at synonymous and nonsynonymous sites showed an excess of fixed nonsynonymous changes, which indicates that the evolution of the Acp29AB protein has been driven by directional selection at least after the split of the D. melanogaster and D. simulans lineages. The pattern of variation in extant populations of D. melanogaster favors a scenario where the fixation of advantageous replacement substitutions occurred in the early stages of speciation and balancing selection is maintaining variation in this species.

Amino Acid Sequence↗

PubMed1999

Natural selection on apical membrane antigen-1 of Plasmodium falciparum.

The Apical Membrane Antigen-1 (AMA-1) is a protein localized in the apical organelles of the merozoite, one of the stages in the life cycle of malaria parasites (Plasmodium spp.) that infects the vertebrate host. This antigen, which is encoded by a single polymorphic locus, plays a role in evading immune detection and mediating invasion into target host cells. We found evidence of positive Darwinian selection on immunogenic regions of P. falciparum AMA-1 favoring genetic diversity in the T-cell epitopes and in regions likely to interact with host antibodies. These results support the hypothesis that polymorphism at the AMA-1 locus in maintained by balancing selection arising from host immune recognition.

Alleles↗

PubMed2001

Deleterious mutations and genetic variation for flower size in Mimulus guttatus.

Mimulus guttatus is a wildflower that exhibits substantial genetic variation in flower size. Here, we test the hypothesis that this variation is caused by deleterious mutations maintained through mutation-selection balance. The deleterious-mutation model predicts that rare, partially recessive alleles will be the primary source of variation. We test this prediction by measuring the change in the mean flower size (deltaM) and the directional dominance of flower size (deltaB) within a selection experiment. If variation is due to rare (partially) recessive alleles, deltaB/deltaM is expected to be positive and exceed one. However, we obtain negative values for deltaB/deltaM from three independent selection lines. This result is statistically inconsistent with the deleterious-mutation model.

Alleles↗

PubMedDate not supplied

Does a parasite have a better chance of survival if an Inuit or a Mayan spits on it?

An earlier puzzling observation [Shields and Mann, J Craiofac Genet Dev Biol, 16:126-136, 1996] that the prevalence of a polymorphic male predominate, major salivary gland-associated, static lesion of the mandible increased exponentially from the Arctic to the Tropics was explained by both positive and negative selection (balancing) on major salivary gland endocrine and exocrine factors. Additional prevalence rates presented here identified three high prevalence high-Temperate zone cultures that were unusually exposed to alimentary parasites. A correlation between macroparasite exposure and the mandibular lesion helped refine the potential selective forces that fashioned major salivary gland size variation. The data suggests that positive selection occurred for androgen-induced enlargement of the suite of major salivary glands and consequently increased quantities of factors. Increased quantities of salivary gland biologically active factors enhance innate protection against infestation of macroparasites per se, especially gut parasites. The data further suggests that negative selection against enlarged salivary glands occurred as protection against electrolyte imbalances in electrolyte stressed environments and in females.

Climate↗

PubMed1986

Contrasting evolutionary histories among tightly linked HLA loci.

Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom association of alleles-make the system of particular interest from the perspective of population genetics. Information on the dynamic evolutionary forces that have acted on a locus can be inferred from the number and distribution of alleles that it carries. Ten loci from the HLA region of the human MHC, each sampled from several different populations, have been examined for departures from the expected value of homozygosity under the condition of selective neutrality. The homozygosities of five class I and II loci that code for membrane glycoproteins, HLA-A, -B, -C, -DR, and -DQ, and of glyoxylase I (GLO) were significantly less than the neutrality expectations. This suggests the presence of some form of balancing selection. In spite of being closely linked, in fact, located between the class I and class II histocompatibility loci, the homozygosities of the four class III or complement loci C2, Bf, C4A, and C4B, which are detected by electrophoresis, were indistinguishable from, or exceeded, that expected under neutrality. Although this conforms to the suggestion that, in general, electrophoretic variants are neutral, because of the tight linkage to loci demonstrating a history of selection, it is possible that the mechanism for generating variation in the class III loci may be different from that of the class I and class II loci.

Alleles↗

PubMed1974

Evidence that enzyme polymorphisms are selectively neutral, but blood group polymorphisms are not.

Data on enzyme polymorphism and blood group polymorphism were examined with special reference to molecular evolution, by using a statistic that depends on neither population structure nor other ecological factors. The data of the former are consistent with the hypothesis of neutral mutant and random genetic drift, whereas the latter are in accord with the hypothesis of balanced selection.

Blood Group Antigens↗

PubMed2002

Measuring immune selection.

Immune responses that kill pathogens or reduce their reproductive rate are generally important in protecting hosts from infection and disease. Pathogens that escape the full impact of such responses will survive, and any heritable genetic basis of this evasion will be selected. Due to the memory component of vertebrate immune responses, pathogens with rare alleles of a target antigen can have an advantage over those with common alleles, leading to the maintenance of a polymorphism. At the genetic level, there ought to be detectable signatures of balancing selection in the genes encoding these antigens. Here, methods for identifying these selective signatures are reviewed. Their practical utility for identifying which antigens are targets of protective immune responses is discussed.

Animals↗

PubMed2000

The evolution of recombination in a heterogeneous environment.

Most models describing the evolution of recombination have focused on the case of a single population, implicitly assuming that all individuals are equally likely to mate and that spatial heterogeneity in selection is absent. In these models, the evolution of recombination is driven by linkage disequilibria generated either by epistatic selection or drift. Models based on epistatic selection show that recombination can be favored if epistasis is negative and weak compared to directional selection and if the recombination modifier locus is tightly linked to the selected loci. In this article, we examine the joint effects of spatial heterogeneity in selection and epistasis on the evolution of recombination. In a model with two patches, each subject to different selection regimes, we consider the cases of mutation-selection and migration-selection balance as well as the spread of beneficial alleles. We find that including spatial heterogeneity extends the range of epistasis over which recombination can be favored. Indeed, recombination can be favored without epistasis, with negative and even with positive epistasis depending on environmental circumstances. The selection pressure acting on recombination-modifier loci is often much stronger with spatial heterogeneity, and even loosely linked modifiers and free linkage may evolve. In each case, predicting whether recombination is favored requires knowledge of both the type of environmental heterogeneity and epistasis, as none of these factors alone is sufficient to predict the outcome.

Alleles↗

PubMed2004

Evidence for abundant slightly deleterious polymorphisms in bacterial populations.

The nearly neutral theory of molecular evolution predicts that slightly deleterious mutations subject to purifying selection are widespread in natural populations, particularly those of large effective population size. To test this hypothesis, the standardized difference between pairwise nucleotide difference and number of segregation sites (corrected for number of sequences) was estimated for 149 population data sets from 84 species of bacteria. This quantity (Tajima's D-statistic) was estimated separately for synonymous (D(syn)) and nonsynonymous (D(non)) polymorphisms. D(syn) was positive in 70% of data sets, and the overall median D(syn) (0.873) was positive. By contrast D(non) was negative in 68% of data sets, and the overall median D(non) (-0.656) was negative. The preponderance of negative values of D(non) is evidence that there are widespread rare nonsynonymous polymorphisms in the process of being eliminated by purifying selection, as predicted to occur in populations with large effective size by the nearly neutral theory. The major exceptions to this trend were seen among surface proteins, particularly those of bacteria parasitic on vertebrates, which included a number of cases of polymorphisms apparently maintained by balancing selection.

Bacteria↗

PubMed2004

Signatures of selection among sex-determining alleles of the honey bee.

Patterns of DNA polymorphisms are a primary tool for dissecting signatures of selection; however, the underlying selective forces are poorly understood for most genes. A classical example of diversifying selection is the complementary sex-determining locus that is found in the very large insect order Hymenoptera (bees, wasps, ants, and sawflies). The gene responsible for sex determination, the complementary sex determiner (csd), has been most recently identified in the honey bee. Females are heterozygous at this locus. Males result when there is only one functional allele present, as a result of either homozygosity (fertilized eggs) or, more commonly, hemizygosity (unfertilized eggs). The homozygotes, diploid males, do not reproduce and have zero fitness, which implies positive selection in favor of rare alleles. Large differences in csd cDNA sequences within and between four populations were found that fall into two major groups, types I and II. Type I consists of several allelic lineages that were maintained over an extended period, an indication of balancing selection. Diversifying selection has operated on several confined parts of the protein, as shown by an excess of nonsynonymous differences. Elevated sequence differences indicate another selected part near a repeat region. These findings have general implications about the understanding of both the function of the multiallelic mechanism and the adaptive processes on the level of nucleotide sequences. Moreover, the first csd sequence data are a notable basis for the avoidance of diploid males in bee selection programs by allele-assisted breeding.

Alleles↗

PubMed2003

Engineered lymphocytes to treat dinitrobenzene sulphonic acid colitis in mice.

Current treatments of inflammatory bowel diseases are limited either by their lack of efficacy or their potential toxicity. In recent years, major advances have been obtained by the development of biological therapies. However, these types of treatment are systemic and can lead to serious adverse events. The new venue of local biological treatments would be most welcome. In this issue of the Journal, Castagliuolo et al. show that lymphocytes engineered to produce TGF-beta1 can reverse dinitrobenzene sulphonic acid-induced colitis in mice. These engineered lymphocytes selectively accumulate in the intestinal mucosa due to the homing properties of their alpha4beta7 integrins, a ligand for MAdCAM1. A local treatment restricted to the inflamed mucosa can thus be obtained. This opens a brand new area of research with the hope of restoring the immunoregulatory balance selectively in the inflamed tissues.

Animals↗

PubMed2003

The mind of primitive anthropologists: hemoglobin and HLA, patterns of molecular evolution.

Frank Livingstone played a central role in defining the population genetics of the sickle cell mutation at position 6 of the human beta globin gene, the most famous amino acid substitution in evolutionary biology. Its discovery occurred at a time when traditional, 19th-century principles of natural selection were being joined with the newly discovered mechanics of DNA structure and protein synthesis to produce Neo-Darwinian theory. When combined with the epidemiology of malaria in Africa, differential mortality for both homozygotes, and the resulting advantage of the heterozygote, sickle cell became the classic balanced polymorphism. Human HLA-A has 237 molecular alleles. The histocompatibility system has as its primary function the presentation of peptides to T-cell receptors and plays an essential role in the immune system. Nearly all of the alleles are codominant and fully functional. Despite almost 30 years of disease-association studies with HLA-A, no convincing evidence has been found for differential fertility or mortality at this locus. Yet the dogma in the histocompatibility field is that this extensive human polymorphism is maintained by "balancing selection." Explaining HLA-A polymorphism is what one might call the sickle-cell-effect. This one mutation, coming as it did at the historical convergence of Darwinian theory and modern genetics, and carrying with it the strong relationship between mutation, disease, and allele frequency, has conditioned our discussion of human genetic variation and population genetics. Has the strength of this early idea made evolutionary biologists uncritical of systems like HLA-A and retarded the search for new mechanisms of molecular evolution? Is it now time to move away from a focus on mutation and polymorphism in evolutionary genetics and toward a systems theory that would explain the origin and evolution of hemoglobin and HLA-A and the biochemical pathways that surround them?

Alleles↗

PubMed2004

Five reasons why inbreeding may have considerable effect on post-reproductive human health.

As the genetic architecture of common complex diseases of late onset is emerging through intensive research, it is intriguing to assess the predicted effect of inbreeding on those diseases. In this paper, we propose five reasons why we believe inbreeding may have a considerable effect on post-reproductive human health. (i) The joint effect of inbreeding depression on all polygenic quantitative phenotypes that confer risk for late-onset diseases is predicted to be multiplicative rather than additive. (ii) The "genetic load" of rare "Mendelian" variants with large deleterious effects in post-reproductive adults is unknown, but could be much greater than expected as these variants were invisible to selection through human history. (iii) Deleterious effects resulting from autozygosity in hundreds of affected rare recessive variants of small effect under common disease/rare variant (CD/RV) hypothesis could result in epistatic effects that could jointly impair capacity to compensate against environmental risks. (iv) Heterozygote advantage in loci under balancing selection could be reduced by inbreeding. (v) Published empirical evidence in animals and humans consistently report large inbreeding effects on late-onset traits. Since inbreeding is common in many populations and the effects of inbreeding depression could substantially contribute to disease burden and reduced life expectancy we believe there is now a clear need for further genetic epidemiological research in humans to investigate this issue.

Animals↗