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Repeat polymorphisms within gene regions: phenotypic and evolutionary implications.

We have developed an algorithm that predicted 11,265 potentially polymorphic tandem repeats within transcribed sequences. We estimate that 22% (2,207/9,717) of the annotated clusters within UniGene contain at least one potentially polymorphic locus. Our predictions were tested by allelotyping a panel of approximately 30 individuals for 5% of these regions, confirming polymorphism for more than half the loci tested. Our study indicates that tandem-repeat polymorphisms in genes are more common than is generally believed. Approximately 8% of these loci are within coding sequences and, if polymorphic, would result in frameshifts. Our catalogue of putative polymorphic repeats within transcribed sequences comprises a large set of potentially phenotypic or disease-causing loci. In addition, from the anomalous character of the repetitive sequences within unannotated clusters, we also conclude that the UniGene cluster count substantially overestimates the number of genes in the human genome. We hypothesize that polymorphisms in repeated sequences occur with some baseline distribution, on the basis of repeat homogeneity, size, and sequence composition, and that deviations from that distribution are indicative of the nature of selection pressure at that locus. We find evidence of selective maintenance of the ability of some genes to respond very rapidly, perhaps even on intragenerational timescales, to fluctuating selective pressures.

Algorithms↗

Theoretical description of the ion transport across nanopores with titratable fixed charges: analogies between ion channels and synthetic pores.

Recently developed nanometer-sized synthetic pores display several properties so far believed to be distinctive features of a large variety of biological wide ion channels. Thus conductance in the pS-nS range, pH-dependent ion selectivity, fluctuations of current between open and closed states, flux inhibition caused by protons or divalent cations, current rectification, and the ability to perform selective macromolecule sizing and counting are found in synthetic and biological channels alike. Despite other differences such as pore size and geometry, the similarities open a new field for exploring specific technological applications via the chemical modification of synthetic pores with biological molecules. This article reviews some of the basic concepts and theories relevant to ion transport in nanopores with titratable charges stressing the analogies between synthetic pores and biological ion channels. The ultimate goal is to show that continuum theories may account for the essential features of these systems. A simple electrodiffusion model and its comparison with experimental results are chosen as a case study.

Ion Channels↗

Classification of hypotheses on the advantage of amphimixis.

A classification of hypotheses on the advantage of amphimixis over apomixis is presented. According to "Immediate Benefit" hypotheses, amphimixis is advantageous regardless of reciprocal gene exchange, because either it directly increases fitness of the progeny, reduces the deleterious mutation rate, or makes selection more efficient. In contrast, "Variation and Selection" hypotheses attribute the advantage of amphimixis to the reciprocal gene exchange that alters genetic variability and response to selection among the progeny. Most such hypotheses assume that amphimixis increases variability and efficiency of selection, but some claim that amphimixis decreases response to selection. Variation and Selection hypotheses require that some factor, either random drift or epistatic selection, makes distributions of different alleles nonindependent, while another factor, either changes of the genotype fitnesses or deleterious mutations, makes overrepresented genotypes non-optimal. Numerous Variation and Selection hypotheses, dealing with either unstructured or spatially structured populations, are reviewed. Two of them seem most plausible: better responsiveness of the amphimictic population to widely fluctuating selection, and lower mutation load in the amphimictic population under synergistic selection against deleterious mutations. In both cases the large advantage of amphimixis requires rather stringent conditions, which could be falsified by careful experiment. Further progress in understanding the evolution of amphimixis will depend mostly on such experimental work.

Environment↗

Sexual dimorphism in relation to current selection in the house finch.

Sexual dimorphism is thought to have evolved in response to selection pressures that differ between males and females. Our aim in this study was to determine the role of current net selection in shaping and maintaining contemporary sexual dimorphism in a recently established population of the house finch (Carpodacus mexicanus) in Montana. We found strong differences between sexes in direction of selection on sexually dimorphic traits, significant heritabilities of these traits, and a close congruence between current selection and observed sexual dimorphism in Montana house finches. Strong directional selection on sexually dimorphic traits and similar intensities of selection in each sex suggested that sexual dimorphism arises from adaptive responses in males and females, with both sexes being far from their local fitness optimum. This pattern is expected when a recently established population experiences continuous immigration from ecologically distinct areas of a species range or as a result of widely fluctuating selection pressures, as found in our study. Strong and sexually dimorphic selection pressures on heritable morphological traits, in combination with low phenotypic and genetic covariation among these traits during growth, may have accounted for close congruence between current selection and observed sexual dimorphism in the house finch. This conclusion is consistent with the profound adaptive population divergence in sexual dimorphism that accompanied very successful colonization of most of the North America by the house finch over the last 50 years.

Adaptation, Physiological↗

Fluctuating environments and the role of mutation in maintaining quantitative genetic variation.

We study a class of genetic models in which a quantitative trait determined by several additive loci is subject to temporally fluctuating selection. Selection on the trait is assumed to be stabilizing but with an optimum that varies periodically and might be perturbed stochastically. The population mates at random, is infinitely large and has discrete generations. We pursue a statistical and numerical approach, covering a wide range of ecological and genetic parameters, to determine the potential of fluctuating environments to maintain quantitative genetic variation. Whereas, in contrast to some recent claims, this potential seems to be rather limited in the absence of recurrent mutation, fluctuating environments might, in combination with it, often generate high levels of additive genetic variation. We investigate how the genetic variation maintained depends on the ecological parameters and on the underlying genetics.

Genetic Variation↗

[Developing robust near infrared calibration models].

There are three approaches to developing robust near infrared calibration models, including spectral pretreatment such as differentiation, Piecewise Multiplicative Scatter Correction (PMSC), Finite Impulse Response (FIR), and Orthogonal Signal Correction (OSC), to remove external variations, selecting wavelengths which are insensitive to external variations, and constructing temperature-hybrid calibration models. In this paper, these three strategies were investigated based on reforming gasoline NIR spectra collected at different temperatures in order to develop robust RON and benzene calibration models against temperature. It has been found that with only spectral pretreatment even OSC method fails to obtain satisfactory results, which could not remove the effects caused by temperature fluctuation. Selecting wavelengths by genetic algorithms and constructing temperature-hybrid calibration models, in which spectra measured at different temperature are combined into one calibration set, are both good approaches to developing robust NIR calibration models against temperature. The latter seems better because it needs no special knowledge and extra software, but thenon-linear effects should be considered in practical applications.

Calibration↗

Genetic hitchhiking.

Selection on one or more genes inevitably perturbs other genes, even when those genes have no direct effect on fitness. This article reviews the theory of such genetic hitchhiking, concentrating on effects on neutral loci. Maynard Smith and Haigh introduced the classical case where the perturbation is due to a single favourable mutation. This is contrasted with the apparently distinct effects of inherited variation in fitness due to loosely linked loci. A model of fluctuating selection is analysed which bridges these alternative treatments. When alleles sweep between extreme frequencies at a rate lambda, the rate of drift is increased by a factor (1 + E[1/pq]lambda/(2(2lambda + r))), where the recombination rate r is much smaller than the strength of selection. In spatially structured populations, the effects of any one substitution are weaker, and only cause a local increase in the frequency of a neutral allele. This increase depends primarily on the rate of recombination relative to selection (r/s), and more weakly, on the neighbourhood size, Nb = 4(pi rho sigma)2. Spatial subdivision may allow local selective sweeps to occur more frequently than is indicated by the overall rate of molecular evolution. However, it seems unlikely that such sweeps can be sufficiently frequent to increase significantly the drift of neutral alleles.

Animals↗

Gene genealogies and population variation in plants.

Early in the development of plant evolutionary biology, genetic drift, fluctuations in population size, and isolation were identified as critical processes that affect the course of evolution in plant species. Attempts to assess these processes in natural populations became possible only with the development of neutral genetic markers in the 1960s. More recently, the application of historically ordered neutral molecular variation (within the conceptual framework of coalescent theory) has allowed a reevaluation of these microevolutionary processes. Gene genealogies trace the evolutionary relationships among haplotypes (alleles) with populations. Processes such as selection, fluctuation in population size, and population substructuring affect the geographical and genealogical relationships among these alleles. Therefore, examination of these genealogical data can provide insights into the evolutionary history of a species. For example, studies of Arabidopsis thaliana have suggested that this species underwent rapid expansion, with populations showing little genetic differentiation. The new discipline of phylogeography examines the distribution of allele genealogies in an explicit geographical context. Phylogeographic studies of plants have documented the recolonization of European tree species from refugia subsequent to Pleistocene glaciation, and such studies have been instructive in understanding the origin and domestication of the crop cassava. Currently, several technical limitations hinder the widespread application of a genealogical approach to plant evolutionary studies. However, as these technical issues are solved, a genealogical approach holds great promise for understanding these previously elusive processes in plant evolution.

Journal Article↗

Symmetry breaking in the collinear phase of the J1-J2 Heisenberg model.

The large J2 limit of the square-lattice J1-J2 Heisenberg antiferromagnet is a classic example of order by disorder where quantum fluctuations select a collinear ground state. Here, we use series expansion methods and a mean-field spin-wave theory to study the excitation spectra in this phase and look for a finite-temperature Ising-like transition, corresponding to a broken symmetry of the square lattice, as first proposed by Chandra et al. [Phys. Rev. Lett. 64, 88 (1990)]]. We find that the spectra reveal the symmetries of the ordered phase. However, we do not find evidence for a finite-T transition. We suggest a scenario for a T=0 transition based on quantum fluctuations.

Journal Article↗

Sexual showiness and parasite load: correlations without parasite coevolutionary cycles.

Hamilton & Zuk (1982, Science 218, 384-387.) produced a model of sexual selection in which coevolutionary cycles of host and parasites generate consistently positive correlations between parent and offspring viability, and that animals choose mates for genetic disease resistance by scrutinizing characters whose full expression is dependent on health and vigour. They predicted a positive correlation between sexual showiness and parasite burden across species, and a negative correlation within a species. First, recent suggestions that interspecific correlations in the opposite direction to that indicated above are consistent with the mechanisms of Hamilton & Zuk's model are discussed. Second, it is shown that the model's predictions can be produced by heritable variation maintained by non-parasite fluctuating selection. In this case, the parasites associated with degree of sexual showiness are those able to amplify any initial heritable differences in vigour. Alternative sources of positive correlation between parent and offspring viability, which include the indirect effects of climatic change and exclude the need for host-parasite coevolutionary cycles, are also proposed.

Animals↗

Environmental origins of sexually selected variation and a critique of the fluctuating asymmetry-sexual selection hypothesis.

Identifying sources of phenotypic variability in secondary sexual traits is critical for understanding their signaling properties, role in sexual selection, and for predicting their evolutionary dynamics. The present study tests for the effects of genotype, developmental temperature, and their interaction, on size and fluctuating asymmetry of the male sex comb, a secondary sexual character, in Drosophila bipectinata Duda. Both the size and symmetry of elements of the sex comb have been shown previously to be under sexual selection in a natural population in northeastern Australia. Two independent reciprocal crosses were conducted at 25 degrees and 29 degrees C between genetic lines extracted from this population that differed in the size of the first (TC1) and third (TC3) comb segments. These temperatures are within the documented range experienced by the species in nature. Additive and dominance genetic effects were detected for TC1, whereas additive genetic, and Y-chromosomal effects were detected for TC3. TC2 and TC3 decreased sharply with increasing temperature, by 10% and 22%, respectively. In contrast, positional fluctuating asymmetry (PFA) significantly increased with temperature, by up to 38%. The results (1) document an important source of environmental variance in a sexual ornament expected to reduce trait heritability in field populations, and thus act to attenuate response to sexual selection, (2) suggest that variation in ornament size reflects differences in male condition; and (3) support the general hypothesis that asymmetry in a sexual ornament is indicative of developmental instability arising from environmental stress. The "environmental heterogeneity" (EH) hypothesis is proposed, and supportive evidence for it presented, to explain negative size-FA correlations in natural populations. Data and theory challenge the use of negative size-FA correlations observed in nature to support the FA-sexual selection hypothesis, which posits that such correlations are driven by differences in genetic quality among individuals.

Analysis of Variance↗

Microbial phenotypic heterogeneity and antibiotic tolerance.

Phenotypic heterogeneity, defined as metastable variation in cellular parameters generated by epigenetic mechanisms, is crucial for the persistence of bacterial populations under fluctuating selective pressures. Diversity ensures that some individuals will survive a potentially lethal stress, such as an antibiotic, that would otherwise obliterate the entire population. The refractoriness of bacterial infections to antibiotic therapy has been ascribed to antibiotic-tolerant variants known as 'persisters'. The persisters are not drug-resistant mutants and it is unclear why they survive antibiotic pressure that kills their genetically identical siblings. Recent conceptual and technological advances are beginning to yield some surprising new insights into the mechanistic basis of this clinically important manifestation of phenotypic heterogeneity.

Anti-Bacterial Agents↗

EP3-2 receptor mRNA expression is reduced and EP3-6 receptor mRNA expression is increased in gravid human myometrium.

OBJECTIVE: To assess relative expression levels of mRNA for EP3 isoforms EP3-2, EP3-3, and EP3-6 in human myometrium in various physiologic states. METHODS: Using semiquantitative reverse transcriptase-polymerase chain reaction, we analyzed myometrial samples from 46 women (ten menopausal, ten nongravid premenopausal, 19 gravidas, seven premenopausal misoprostol-treated nongravid women) for the specific expression of mRNA messages for the EP3 receptor isoforms EP3-2, EP3-3, and EP3-6. RESULTS: We found that the expression of EP3-2 was significantly lower in gravid than nongravid myometrium (P < .0001). Levels of the EP3-6 message were higher in gravid samples than in nongravid specimens (P < .02). EP3-3 mRNA was present in higher levels in menopausal samples compared with the other groups. CONCLUSIONS: The selective fluctuation of mRNA expression of the different EP3 isoforms suggests the possibility of an important regulatory role for these receptors in myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of EP3 receptor isoforms in human myometrium.

Adult↗

Suboptimal timing of reproduction in Lobelia inflata may be a conservative bet-hedging strategy.

Age and size at reproduction are important components of fitness, and are variable both within and among angiosperm species. The fitness consequences of such life-history variation are most readily studied in organisms that reproduce only once in their lifetime. The timing of the onset of reproduction (bolting) in the monocarpic perennial, Lobelia inflata, occurs over a range of dates within a season, and may be postponed to a later year. Empirical relationships among life-history traits, derived from over 950 wild-growing and experimentally manipulated plants in the field, are used to model an optimal changing size threshold (norm of reaction) for bolting over the growing season. Comparisons are made between observed and expected norms of reaction governing bolting. An apparently suboptimal bolting schedule that precludes bolting beyond an early (conservative) date is observed, and is found to be qualitatively consistent with conservative bet hedging under unpredictable season lengths. On this basis we propose the schedule of bolting as a plausible example of a conservative bet-hedging strategy. The results underscore the critical need for long-term studies of fluctuating selection to distinguish suboptimality from bet hedging.

Adaptation, Biological↗

Isolation and characterization of mutants of human diploid fibroblasts resistant to diphtheria toxin.

Stable mutants highly resistant to the protein synthesis inhibitor diphtheria toxin (dipr) have been selected in human diploid fibroblast cells at a frequency of 1-8 X 10(-6). Treatment of cells with mutagens, (e.g., ethylmethanesulfonate, nitrosoguanidine, and ICR-170), increased the frequencies of dipr mutants by 50- to 500-fold in different experiments, and the optimal expression time for dipr mutation was about 5 days. All mutants examined thus far have bred true, and no effects of cell density or cross feeding have been observed on the selection. Fluctuation analysis showed that the dipr mutation occurs in these fibroblasts at the rate of 5-6 X 10(-7) mutations per cell per generation. Protein synthesis in mutant extracts was resistant to diphtheria toxin, indicating that the dipr lesion in such mutants lies in the protein synthesis machinery. The characteristics of the dipr marker should make this system particularly useful for studies of quantitative mutagenesis in human diploid cells.

Cell Line↗

Hierarchical analysis of population genetic variation in mitochondrial and nuclear genes of Daphnia pulex.

The geographic structure of Daphnia pulex populations from the central United States is analyzed with respect to isozyme and mitochondrial DNA variation. The species complex consists of cyclic and obligate parthenogens. A hierarchical analysis of population structure in the cyclic parthenogens by using a fixation-index approach indicates that this is one of the most extremely subdivided species yet studied. This genetic structure, much of which accrues within 100 km, is certainly due in part to the limited dispersal ability of Daphnia. However, previous work has shown that fluctuating selection can account for the spatial heterogeneity in isozyme frequencies in these populations. This may explain why the population subdivision for the mitochondrial genome increases approximately three times as rapidly with distance as does that for nuclear genes, which is slower than the neutral expectation. The obligate parthenogens are shown to be polyphyletic in origin, evolutionarily young, and, in some cases, geographically widespread.

Animals↗

Heterogeneity in stable isotope profiles predicts coexistence of populations of barn swallows Hirundo rustica differing in morphology and reproductive performance.

Population studies assume that individuals belonging to a study population are homogeneous for natal and breeding origin, although this assumption is rarely tested. We tested for heterogeneity in stable-isotope profiles (delta15N, delta13C, deltaD) of feathers grown in the African winter quarters from a Danish breeding population of adult barn swallows, Hirundo rustica. Deuterium isotope values did not provide useful information on population segregation of wintering swallows in Africa. However, both delta15N and delta13C values showed a clearly bimodal distribution with 6% belonging to one category and the remaining birds belonging to another category, resulting in this population comprising three categories of birds. Adults belonging to the two categories of delta13C isotope profiles differed weakly in morphology for several different characters. The frequency and the size of second broods differed between categories of delta13C isotope profiles. Phenotypes of nestlings from the first brood in terms of tarsus length, body mass and T-cell response differed significantly between the two delta15N isotope categories, suggesting that conditions during winter carried over to the breeding season at least as late as the first brood. Polymorphism can be maintained only if fitness is similar for birds from categories of isotope profiles. We suggest that fluctuating selection or migration-selection balance may maintain the observed polymorphism.

Analysis of Variance↗

Molecular genetic variation and individual survival during population crashes of an unmanaged ungulate population.

Theoretical models of the effect of population bottlenecks on genetic variation assume that individuals are removed at random from the population. We investigated this assumption in a naturally regulated, unstable population of Soay sheep (Ovis aries). During rapid population declines or 'crashes', individuals were not removed at random with respect to genotype: we found associations between individual survival and certain genotypes at five polymorphic protein or microsatellite DNA loci (Ada, Got, Tf, MAF18 and OPACAP). Some loci appeared to show simple associations with survival whereas others had more complex interactions with crash year or age: all displayed different patterns of association between the sexes. Simple overdominance was not a general feature of our data; it seems likely that fluctuating selecting, countervailing selection in different fitness components or frequency-dependent selection may explain the pattern and complexity of the associations shown at different loci. Our study cannot distinguish between selection acting at these loci or at other, closely linked loci. However, our empirical study implies that the molecular genetic outcome of population bottlenecks in natural populations does not always follow theoretical expectations based on the random removal of genotypes. Bottlenecks in which individuals are removed at random are distinct from bottlenecks in which there is scope for selection via non-random survival of individuals.

Alleles↗