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Dissecting fluctuating selection: A unified population and quantitative genetics framework.

One of the longstanding debates in evolutionary biology is the effect of fluctuating selection on genetic changes in populations. However, the extent to which these periodic forces influence organisms at both genomic and phenotypic levels remains unclear. Despite the compelling evidence of fluctuating selection from recent studies, there is a disconnect between empirical and theoretical findings concerning the underlying mechanisms due to the limited evidence regarding the scale and processes that generate genome-wide oscillations. This study aims to elucidate how both genetic factors (e.g. heritability, number of causative loci) and ecological factors (e.g. season length, the difference in the phenotypic optima between seasons, population size dynamics) drive fluctuating selection and to identify the parameters that produce consistent oscillatory patterns. We developed a modeling framework integrating quantitative and population genetics to simulate a population under various selection regimes. We applied spectral analysis to detect periodicity, indicating cyclical selective environments. Our simulations highlight the conditions sustaining oscillations in allele frequencies over time. Spectral analysis successfully identifies the periodic patterns from allele frequency trajectories, even under highly complex selection regimes. Not only does our study clarify the conditions that yield oscillatory behaviors, but these parameters can also potentially be estimated in natural populations, providing a possibility of empirically testing these models.

Fluctuating selection

Dissecting fluctuating selection: A unified population and quantitative genetics framework.

One of the longstanding debates in evolutionary biology is the effect of fluctuating selection on genetic changes in populations. However, the extent to which these periodic forces influence organisms at both genomic and phenotypic levels remains unclear. Despite the compelling evidence of fluctuating selection from recent studies, there is a disconnect between empirical and theoretical findings concerning the underlying mechanisms due to the limited evidence regarding the scale and processes that generate genome-wide oscillations. This study aims to elucidate how both genetic factors (e.g. heritability, number of causative loci) and ecological factors (e.g. season length, the difference in the phenotypic optima between seasons, population size dynamics) drive fluctuating selection and to identify the parameters that produce consistent oscillatory patterns. We developed a modeling framework integrating quantitative and population genetics to simulate a population under various selection regimes. We applied spectral analysis to detect periodicity, indicating cyclical selective environments. Our simulations highlight the conditions sustaining oscillations in allele frequencies over time. Spectral analysis successfully identifies the periodic patterns from allele frequency trajectories, even under highly complex selection regimes. Not only does our study clarify the conditions that yield oscillatory behaviors, but these parameters can also potentially be estimated in natural populations, providing a possibility of empirically testing these models.

Fluctuating selection

Effect of temporal fluctuation of selection coefficient on gene frequency in a population.

The diffusion equations describing the change of gene frequencies are extended to indlude the effect of temporal fluctuation of selection coefficient that may persist for some generations. The equilibrium distribution of gene frequencies and the fixation probability of a mutant gene are obtained from the extended equations. Comparison is made with the experimental data on protein polymorphism. A possible bearing of the fluctuation of selection coefficient on the problem of molecular evolution is discussed in relation to the neutral theory.

Gene Frequency

Seasonal fluctuations in fitness result in severe reductions in effective population size.

Genetic evidence for fluctuating selection has begun to accumulate for different species over the past few decades, especially for the Drosophila genus where studies have reported hundreds of loci undergoing putatively adaptive oscillations across successive seasons. However, most theoretical and simulation studies of fluctuating selection have relied on abstract or weakly parameterized models, making it difficult to assess their relevance for natural populations. In this study, we simulate multilocus seasonally fluctuating selection under a recently developed model and examine its effect on the variance effective population size (Ne ) at a genome-wide scale. By recapitulating genomic, demographic, and evolutionary parameters from natural Drosophila populations in our simulations, we were able to reproduce allele frequency oscillations reported in recent studies and show that these lead to ~50% genome-wide reductions in Ne . We also demonstrate that Ne reductions are well predicted by the maximum frequency amplitude among all adaptively fluctuating loci, and that the frequency amplitudes are largely determined by the number of adaptively fluctuating loci and the strength of their epistatic interactions. Our results demonstrate that fluctuating selection can substantially reduce effective population size and underscore the importance of temporally variable selection in shaping genome-wide patterns of variation beyond classical models.

Drosophila melanogaster

Seasonal fluctuations in fitness result in severe reductions in effective population size.

Genetic evidence for fluctuating selection has begun to accumulate for different species over the past few decades, especially for the Drosophila genus where studies have reported hundreds of loci undergoing putatively adaptive oscillations across successive seasons. However, most theoretical and simulation studies of fluctuating selection have relied on abstract or weakly parameterized models, making it difficult to assess their relevance for natural populations. In this study, we simulate multilocus seasonally fluctuating selection acting on standing genetic variation under a recently developed model and examine its effect on the variance effective population size (Ne) at a genome-wide scale. By recapitulating genomic, demographic, and evolutionary parameters from natural Drosophila populations in our simulations, we were able to reproduce allele frequency oscillations reported in recent studies and show that these lead to ∼50% genome-wide reductions in Ne. We also demonstrate that Ne reductions are well predicted by the maximum frequency amplitude among all adaptively fluctuating loci, and that the frequency amplitudes are largely determined by the number of adaptively fluctuating loci and the strength of their epistatic interactions. Our results demonstrate that fluctuating selection can substantially reduce effective population size and underscore the importance of temporally variable selection in shaping genome-wide patterns of variation beyond classical models.

Drosophila melanogaster

Pervasive fitness trade-offs revealed by rapid adaptation to shifting population densities in large experimental populations of Drosophila melanogaster.

Trade-offs are an inherent feature of organismal biology that are expected play a fundamental role in the evolution of natural populations. Efforts to quantify trade-offs are largely confined to phenotypic measurements and the identification of negative genetic-correlations among fitness-relevant traits. Here, we use time-series genomic data collected during experimental evolution in large, genetically diverse populations of Drosophila melanogaster to directly measure the manifestation of trade-offs in response to fluctuating selection on ecological timescales. Specifically, we first conducted a lab-based selection experiment to quantify a genome-wide signal of antagonistic pleiotropy elicited in response to shifting population densities and associated with reproduction and stress tolerance selection. In doing so, we identified a putative role of two cosmopolitan inversions in these trade-offs. We then conducted an independent experiment to show that a simple manipulation of increasing population density under controlled lab-based conditions identified loci that are relevant to selection during population expansion and collapse in a complex, semi-natural setting. In concert, our results reveal how adaptation in complex, natural environments can be coarse-grained in such a manner to drive repeatable and predictable patterns of genomic variation, and further add credence to models positing a role of generic fitness trade-offs in the maintenance of variation in natural populations.

Drosophila melanogaster

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

The ecology and evolution of microbial immune systems: a look on the wild vibrio side.

Natural populations of vibrio beyond the well-studied pandemic strains of Vibrio cholerae, provide a powerful model for investigating the eco-evolutionary dynamics of microbial immune systems. Their genetic diversity, ecological versatility, ease of culturability and the availability of time-series data enable detailed studies of phage-host interactions in natural contexts. This review synthesizes recent advances in vibriophage research, highlighting key findings and emerging tools. High-throughput assays and genomic tools have offered new perspectives on phage specificity, host range and the evolutionary pressures shaping these interactions. Theoretical frameworks, such as arms race and fluctuating selection dynamics, are informed by empirical data from vibrio-phage systems, with time-series sampling providing crucial insights into their temporal and spatial dynamics. A major finding is the role of mobile genetic elements (MGEs) in encoding bacterial defence systems, which shape phage-host coevolution. Discoveries like the phage satellite PICMI illustrate how MGEs facilitate the transfer of antiviral systems, influencing ecological and evolutionary dynamics. The paradox of generalist vibriophages, rare despite their broad host ranges, is also explored. By integrating experimental approaches with field observations, vibriophage research advances microbial ecology and informs sustainable applications in aquaculture and phage therapy, reinforcing vibrios as a versatile model system.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.

Bacteriophages

Heat stress, fluctuating asymmetry and prenatal selection in the laboratory rat.

Recent studies have demonstrated that stress may increase the fluctuating asymmetry of teeth and limbs in laboratory animals. The present study investigates the effects of heat on such parameters. Pregnant laboratory rats are exposed to temperatures of 33 degrees C during gestation. Increases in fluctuating asymmetry of dental dimensions as well as bone density are found for the pups of such females when compared to unstressed controls. A general increase in limb lengths is also reported for young of heat stressed animals. Prenatal selection with differential survival is suggested as a possible explanation for differences found between the experimental and control animals.

Animals

Life-history tactics: a review of the ideas.

This review organizes ideas on the evolution of life histories. The key life-history traits are brood size, size of young, the age distribution of reproductive effort, the interaction of reproductive effort with adult mortality, and the variation in these traits among an individual's progeny. The general theoretical problem is to predict which combinations of traits will evolve in organisms living in specified circumstances. First consider single traits. Theorists have made the following predictions: (1) Where adult exceeds juvenile mortality, the organism should reproduce only once in its lifetime. Where juvenile exceeds adult mortality, the organism should reproduce several times. (2) Brood size should macimize the number of young surviving to maturity, summed over the lifetime of the parent. But when optimum brood-size unpredictably in time, smaller broods should be favored because they decrease the chances of total failure on a given attempt. (3) In expanding populations, selection should minimize age at maturity. In stable populations, when reproductive success depends on size, age, or social status, or when adult exceeds juvenile mortality, then maturation should be delayed, as it should be in declining populations. (4) Young should increase in size at birth with increased predation risk, and decrease in size with increased resource availability. Theorists have also predicted that only particular combinations of traits should occur in specified circumstances. (5) In growing populations, age at maturity should be minimized, reproductive effort concentrated early in life, and brood size increased. (6) One view holds that in stable environments, late maturity, broods, a few, large young, parental care, and small reproductive efforts should be favored (K-selection). In fluctuating environments, early maturity, many small young, reduced parental care, and large reproductive efforts should be favored (r-selection). (7) But another view holds that when juvenile mortality fluctuates more than adult mortality, the traits associated with stable and fluctuating environments should be reversed. We need experiments that test the assumptions and predictions reviewed here, more comprehensive theory that makes more readily falsifiable predictions, and examination of different definitions of fitness.

Age Factors

The role of allergy in fluctuating hearing loss.

A method for the selection of patients with fluctuating hearing loss and Meniere's disease for allergic evaluation is presented. An approach to the diagnosis and treatment of these problems is reviewed. Seventy-two patients with Meniere's disease who met the criteria of the American Academy Subcommittee on Equilibrium and Its Measurements were evaluated. Thirty-two per cent of the 62 patients receiving allergy therapy or allergy and metabolic therapy responded to treatment. Half required a combination of metabolic and allergy management, whereas the other half responded to allergy therapy alone.

Food Hypersensitivity

[Genetic analysis of the resistance of mouse somatic cells to colchicine].

The genetic nature of the resistance of mouse L cells to 0.06 microgram/ml of colchicine (the first step of selection) was studied. Fluctuation tests showed that the generation of drug-resistant variants in the wild type population was random and did not depend on the action of the selective agent. The rate of spontaneous occurrence of this variants was approximately 2 . 10(-5) per cell per generation. Colchicine resistance proved to be relatively unstable: it was 2--3-fold less in all clones propagated in non-selective conditions for 25--33 days. Two mutagens, ethylmethanesulphonate and N-nitroso-N-methylurea, failed to induce colchicine resistance in conditions when they enhanced the frequency of 8-azaguanine-resistant cells 10-fold.

Cell Survival

Duration of hospitalization for bacteremic infections at Boston City Hospital during 12 selected years between 1935 and 1972.

In survivors of both community-acquired (CA) and hospital-acquired (HA) bacteremic infections at Boston City Hospital during 12 selected years between 1935 and 1972, the mean hospital stay fluctuated widely from one selected year to the next, but it was generally shorter and early discharges were more frequent in the years when effective antibacterial agents were used. The greatest reduction in hospital stay occurred by 1941. The size of the fluctuations and reductions also varied with the causative organism. The average duration of hospitalization of all survivors of HA bacteremic infections after the first positive blood culture was 10.5 days longer than the total hospitalization of survivors of CA infections. The reduced length of hospital stay after 1935 is attributed to the successful use of effective antibacterial drugs, and the greater effect in CA than in HA cases is attributed to more frequent infections in the latter with organisms resistant to those drugs.

Boston

Evidence for selection by male mating success in natural populations of Drosophila pseudoobscura.

Gene arrangement frequencies were determined at two stages in the life history of Drosophila pseudoobscura taken from nature. Three populations in the central highlands of Mexico were each sampled twice during 1976. Gene arrangement frequencies were measured in adult males and in larvae that were the offspring of females collected at the same time. The adult males were in all likelihood a representative sample of those who fathered the larvae produced by the wild females. Differences in gene arrangement frequency between these two life stages should indicate the operation of natural selection. One-third of our comparisons of common gene arrangement frequencies in males and in larvae from the next generation were statistically significant, as were one-third of our comparisons of total frequency arrays in the two life stages. We consider the components of selection that could produce such frequency changes and reason that male mating success must be the major one. Gene arrangement frequencies in the Mexican populations fluctuate within wide bounds. Selection must act to retain the polymorphism in the face of this flux in gene arrangement frequencies, and we suggest that male mating success plays an important role.

Animals

Finlay-Wilkinson random regression for yield and yield stability prediction in cereals.

Year-to-year climate variability poses a challenge for agriculture by increasing crop yield variability; therefore, there is a need to identify genotypes that can withstand these fluctuations. With the right selection criteria, genotypes with yield stability across variable environmental conditions can be selected. Methods such as Finlay-Wilkinson random regression (FWRR) may allow us to use sparse datasets-common in plant breeding pipelines-and incorporate genomic data to leverage phenotypic information from related genotypes to predict yield stability. Our objective was to examine how the number of environments and the variance among those environments affect stability predictions. We also integrate FWRR as a genomic prediction tool for characterizing yield stability, comparing it to the traditional genomic prediction models as a reference. We used three datasets: one highly unbalanced dataset for oats (Avena sativa L.) and two completely balanced datasets with different numbers of environments for barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.). We fit standard Finlay-Wilkinson (FW) and FWRR models to estimate grain yield and stability under various scenarios. We found that the estimated stability values obtained were similar using balanced datasets for FW or FWRR. FWRR also achieved moderate predictive ability for stability using unbalanced datasets under 10-fold cross-validation (CV1) with new genotypes. In terms of environmental representation, selecting the right set of environments for inclusion in the model was more important than adding more environments. Our results suggest the possibility of using FWRR to select stable genotypes earlier in line development, as well as to design resource-efficient stability-testing schemes.

Hordeum

Interactions of Folch-Lees proteolipid apoprotein with planar lipid bilayers.

Water-soluble Folch-Lees proteolipid apoprotein from bovine CNS white matter induces a voltage-dependent conductance in black lipid membranes. Na+ is required for the induced conductance change but the established conductance has very low ionic selectivity. The induced conductance fluctuates with a minimum amplitude of 10(-11)--10(-10) mho. The magnitude of the conductivity change is dependent on protein concentration and on the composition of lipid bilayers. At a fixed voltage the induced conductance of a phosphatidylcholine-cholesterol membrane is proportional to the sixth power of the protein concentration and the first power of Na+ concentration. The interactions between the apoprotein and the lipids are both electrostatic and hydrophobic, but the interaction leading to the conductance increase appears to be mainly hydrophobic. Both the increase in conductance and the current fluctuations remain after extensive washing of the chambers to remove the protein. Furthermore, pronase or glutaraldehyde added to either the cis or trans side of the membrane does not affect the apoprotein-established conductance. However, if the bilayer is formed in the presence of both the apoprotein and pronase or if the apoprotein is treated with pronase prior to its addition to the chamber, no conductance change is observed. The association of the apoprotein with the membrane thus appears to render the protein inaccessible to proteolytic digestion, suggesting that the apoprotein is at least partially imbedded in the membrane interior.

Animals