Conditions for Protected Inversion Polymorphism under Supergene Selection

Conditions for protected inversion polymorphism under the operation of both karyotype and supergene selection in a viability model have been analytically determined. When supergene selection (the effect of recombination in homokaryotypes lowering the mean fitness of their offspring) is acting on gene arrangements and there is no karyotype selection, it is demonstrated that a polymorphic stable equilibrium is reached by the population, which is a function of only the recombination effects in homokaryotypes. Under both supergene and karyotype selection the degree of dominance (h) of karyotype selection is critical to produce a protected inversion polymorphism. In general, the opportunity for protected polymorphism increases as the degree of dominance decreases. For small s values, the conditions for protected polymorphism are r > 2sh and c > 2s(h - 1), where r and c are the average loss of viability for offspring of ST/ST and IN/IN homokaryotypes, respectively. These findings suggest that supergene selection may be an important balancing mechanism contributing to the maintenance of inversion polymorphism.     

Why are some snails visibly polymorphic,and others not?

Work on Cepaea land-snails since 1950 is surveyed, and various explanations for their visible polymorphism, including predator selection, the influence of sunlight and temperature, co-adaptation and linkage disequilibrium, and "area effects", are discussed. All of these can modify the genetic make-up of natural populations in particular circumstances, but none provide a satisfactory answer to the question of why some species are visibly polymorphic whereas others present a uniform external appearance. The likely explanation is that probably all species are genetically heterogeneous at numerous loci, as a result of heterozygote advantage, co-adaptation and other selective factors maintaining the different alleles in equilibrium, which may sometimes have visible effects on the phenotype. If these are positively disadvantageous, selection for epistatic genes will suppress the visible polymorphism, without affecting the underlying genetical heterogeneity, preserved by selection for other non-visible pleiotropic effects of the alleles involved. But this will not happen if the visibly distinct effects of these different allelomorphs are selectively more or less neutral. Many examples of polymorphism, including the so-called 'pseudo'-polymorphism, are therefore essentially non-adaptive so far as their visible manifestation is concerned, being maintained as balanced polymorphism by selection for non-visible pleiotropic effects of the genes involved.     

Partial protection from cyclical selection generates a high level of polymorphism at multiple non‐neutral sites

Temporally varying selection is known to maintain genetic polymorphism under certain restricted conditions. However, if part of a population can escape from selective pressure, a condition called the “storage effect” is produced, which greatly promotes balanced polymorphism. We investigate whether seasonally fluctuating selection can maintain polymorphism at multiple loci, if cyclically fluctuating selection is not acting on a subpopulation called a “refuge.” A phenotype with a seasonally oscillating optimum is determined by alleles at multiple sites, across which the effects of mutations on phenotype are distributed randomly. This model resulted in long‐term polymorphism at multiple sites, during which allele frequencies oscillate heavily, greatly increasing the level of nonneutral polymorphism. The level of polymorphism at linked neutral sites was either higher or lower than expected for unlinked neutral loci. Overall, these results suggest that for a protein‐coding sequence, the nonsynonymous‐to‐synonymous ratio of polymorphism may exceed one. In addition, under randomly perturbed environmental oscillation, different sets of sites may take turns harboring long‐term polymorphism, thus making trans‐species polymorphism (which has been predicted as a classical signature of balancing selection) less likely.     

Genomic Imprinting Leads to Less Selectively Maintained Polymorphism on X Chromosomes

Population-genetic models are developed to investigate the consequences of viability selection at a diallelic X-linked locus subject to genomic imprinting. Under complete paternal-X inactivation, a stable polymorphism is possible under the same conditions as for paternal-autosome inactivation with differential selection on males and females. A necessary but not sufficient condition is that there is sexual conflict, with selection acting in opposite directions in males and females. In contrast, models of complete maternal-X inactivation never admit a stable polymorphism and alleles will either be fixed or lost from the population. Models of complete paternal-X inactivation are more complex than corresponding models of maternal-X inactivation, as inactivation of paternally derived X chromosomes in females screens these chromosomes from selection for a generation. We also demonstrate that polymorphism is possible for incomplete X inactivation, but that the parameter conditions are more restrictive than for complete paternal-X inactivation. Finally, we investigate the effects of recurrent mutation in our models and show that deleterious alleles in mutation–selection balance at imprinted X-linked loci are at frequencies rather similar to those with corresponding selection pressures and mutation rates at unimprinted loci. Overall, our results add to the reasons for expecting less selectively maintained allelic variation on X chromosomes.     

Allelic Genealogy under Overdominant and Frequency-Dependent Selection and Polymorphism of Major Histocompatibility Complex Loci

To explain the long-term persistence of polymorphic alleles (trans-specific polymorphism) at the major histocompatibility complex (MHC) loci in rodents and primates, a computer simulation study was conducted about the coalescence time of different alleles sampled under various forms of selection. At the same time, average heterozygosity, the number of alleles in a sample, and the rate of codon substitution were examined to explain the mechanism of maintenance of polymorphism at the MHC loci. The results obtained are as follows. (1) The coalescence time for neutral alleles is too short to explain the trans-specific polymorphism at the MHC loci. (2) Under overdominant selection, the coalescence time can be tens of millions of years, depending on the parameter values used. The average heterozygosity and the number of alleles observed are also high enough to explain MHC polymorphism. (3) The pathogen adaptation model proposed by Snell is incapable of explaining MHC polymorphism, since the coalescence time for this model is too short and the expected heterozygosity and the expected number of alleles are too small. (4) From the mathematical point of view, the minority advantage model of frequency-dependent selection is capable of explaining a high degree of polymorphism and trans-specific polymorphism. (5) The molecular mimicry hypothesis also gives a sufficiently long coalescence time when the mutation rate is low in the host but very high in the parasite. However, the expected heterozygosity and the expected number of alleles tend to be too small. (6) Consideration of the molecular mechanism of the function of MHC molecules and other biological observations suggest that the most important factor for the maintenance of MHC polymorphism is overdominant selection. However, some experiments are necessary to distinguish between the overdominance and frequency-dependent selection hypotheses.     

Cyclical environmental changes as a factor maintaining genetic polymorphism. 1. Two-locus haploid selection

To classify different types of cyclic selection, a measure of fitness disequilibrium was used, and a class of systems were considered where this measure has the same sign in all states (sign-concordant environments). The necessary conditions for existence of a fixed point (considering any moment within the period as a referring one) are obtained for sign-concordant systems. However, analytical study of such systems, in the case of selection for equal additive genes, and numerical testing of more general situations, allowed us to conclude that no polymorphism is possible. In the alternative class of sign-concordant systems, polymorphism is possible. However, we found that global stability is an exception rather than a rule for sign-nonconcordant systems. Massive numerical simulations of selection in a four-state environment were made for cycle lengths in the range 8–28 and with evenly distributed selection coefficients. The proportion of polymorphic regimes ranged up to about 1.5%, and was dependent on the recombination rate between the loci. It should be stressed, that polymorphism maintenance in the haploid systems, when it is possible, can not be considered as an effect derived from constant selection, or be a result of any hidden form of heterozygous advantage. In other words, polymorphism stability is causally connected with environmental fluctuations. Equally important is that this effect of fluctuations is only possible because of recombination: in single locus systems haploid cyclical selection is unable to produce protected polymorphism.     

On the maintenance of sex chromosome polymorphism by sex-antagonistic selection

Complex sex determination systems are a priori unstable and require specific selective forces for their maintenance. Analytical derivations suggest that sex antagonistic selection may play such a role, but this assumes absence of recombination between the sex-determining and sex-antagonistic genes. Using individual-based simulations and focusing on the sex chromosome and coloration polymorphisms of platy fishes as a case study, we show that the conditions for polymorphism maintenance induce female biases in primary sex ratios, so that sex ratio selection makes the system collapse toward male or female heterogamety as soon as recombinant genotypes appear. However, a polymorphism can still be maintained under scenarios comprising strong sexual selection against dull males, mild natural selection against bright females, and low recombination rates. Though such conditions are plausibly met in natural populations of fishes harboring such polymorphisms, quantitative empirical evaluations are required to properly test whether sex antagonistic selection is a causal agent or whether other selective processes are required (such as local mate competition favoring female-biased sex ratios).     

Patterns of selection and polymorphism of innate immunity genes in bumblebees (Hymenoptera: Apidae)

In response to on-going biodiversity loss, conservation genetics has established itself as an important branch of biology. Historically concentrating on assessing stochastic processes using neutral loci, there has been a recent surge of interest in understanding and quantifying variation at loci underlying ecologically important traits. To this end, patterns of selection and polymorphism at these loci must be characterized. Loci underlying immunity make good candidates in this context: they are expected to be important for population persistence and may exhibit diversifying or divergent selection. Predictions regarding the pattern of selection expected at immune system loci have been based on their interactions with pathogens, however, published studies report mixed results as to whether these are borne out or not. Here, polymorphism and selection is examined for three innate immune system loci in bumblebees: a peptidoglycan recognition protein, a putative alpha-macroglobulin, and scavenger receptor. Both intra- and inter-specific sequence variation is quantified. Very little polymorphism was encountered, precluding robust tests of selection. However, the lack of inter-specific polymorphisms suggests a lack of positive selection for the regions sequenced. Results are discussed with respect to population genetic predictions and generation of a specific immune response in insects. Alternative loci and methods for studying adaptive genetic variation in a conservation context are considered.     

The probability and chromosomal extent of trans-specific polymorphism

Balancing selection may result in trans-specific polymorphism: the maintenance of allelic classes that transcend species boundaries by virtue of being more ancient than the species themselves. At the selected site, gene genealogies are expected not to reflect the species tree. Because of linkage, the same will be true for part of the surrounding chromosomal region. Here we obtain various approximations for the distribution of the length of this region and discuss the practical implications of our results. Our main finding is that the trans-specific region surrounding a single-locus balanced polymorphism is expected to be quite short, probably too short to be readily detectable. Thus lack of obvious trans-specific polymorphism should not be taken as evidence against balancing selection. When trans-specific polymorphism is obvious, on the other hand, it may be reasonable to argue that selection must be acting on multiple sites or that recombination is suppressed in the surrounding region.     

MDH-polymorphism in Drosophila subobscura: I. Selection and hitch-hiking in laboratory populations

Summary The interrelation of genic polymorphism at the Malate dehydrogenase (Mdh)-locus and chromosomal polymorphism for superimposed gene arrangements was studied in 5 experimental populations of Drosophila subobscura. It could be shown that chromosomal polymorphism is maintained by balancing selection in favour of the heterozygotes. In contrast, selection at the Mdh-locus itself seems to be of minor importance. The changes of frequency observed for the Mdh-alleles are most probably due to hitch-hiking on the gene blocks enclosed by the chromosomal structures or to selection for tightly linked genes rather than to fitness differences between Mdh-genotypes. The results may be considered as a model for the situation found in natural populations of D. subobscura.     

Pervasive Hitchhiking at Coding and Regulatory Sites in Humans

Much effort and interest have focused on assessing the importance of natural selection, particularly positive natural selection, in shaping the human genome. Although scans for positive selection have identified candidate loci that may be associated with positive selection in humans, such scans do not indicate whether adaptation is frequent in general in humans. Studies based on the reasoning of the MacDonald–Kreitman test, which, in principle, can be used to evaluate the extent of positive selection, suggested that adaptation is detectable in the human genome but that it is less common than in Drosophila or Escherichia coli. Both positive and purifying natural selection at functional sites should affect levels and patterns of polymorphism at linked nonfunctional sites. Here, we search for these effects by analyzing patterns of neutral polymorphism in humans in relation to the rates of recombination, functional density, and functional divergence with chimpanzees. We find that the levels of neutral polymorphism are lower in the regions of lower recombination and in the regions of higher functional density or divergence. These correlations persist after controlling for the variation in GC content, density of simple repeats, selective constraint, mutation rate, and depth of sequencing coverage. We argue that these results are most plausibly explained by the effects of natural selection at functional sites—either recurrent selective sweeps or background selection—on the levels of linked neutral polymorphism. Natural selection at both coding and regulatory sites appears to affect linked neutral polymorphism, reducing neutral polymorphism by 6% genome-wide and by 11% in the gene-rich half of the human genome. These findings suggest that the effects of natural selection at linked sites cannot be ignored in the study of neutral human polymorphism.     

Natural selection at linked sites in humans

Theoretical and empirical work indicates that patterns of neutral polymorphism can be affected by linked, selected mutations. Under background selection, deleterious mutations removed from a population by purifying selection cause a reduction in linked neutral diversity. Under genetic hitchhiking, the rise in frequency and fixation of beneficial mutations also reduces the level of linked neutral polymorphism. Here we review the evidence that levels of neutral polymorphism in humans are affected by selection at linked sites. We then discuss four approaches for distinguishing between background selection and genetic hitchhiking based on (i) the relationship between polymorphism level and recombination rate for neutral loci with high mutation rates, (ii) relative levels of variation on the X chromosome and the autosomes, (iii) the frequency distribution of neutral polymorphisms, and (iv) population-specific patterns of genetic variation. Although the evidence for selection at linked sites in humans is clear, current methods and data do not allow us to clearly assess the relative importance of background selection and genetic hitchhiking in humans. These results contrast with those obtained for Drosophila, where the signals of positive selection are stronger.     

Microhabitat variation and sexual selection can maintain male color polymorphisms

Male color polymorphism may be an important precursor to sympatric speciation by sexual selection, but the processes maintaining such polymorphisms are not well understood. Here, we develop a formal model of the hypothesis that male color polymorphisms may be maintained by variation in the sensory environment resulting in microhabitat-specific selection pressures. We analyze the evolution of two male color morphs when color perception (by females and predators) is dependent on the microhabitat in which natural and sexual selection occur. We find that an environment of heterogeneous microhabitats can lead to the maintenance of color polymorphism despite asymmetries in the strengths of natural and sexual selection and in microhabitat proportions. We show that sexual selection alone is sufficient for polymorphism maintenance over a wide range of parameter space, even when female preferences are weak. Polymorphisms can also be maintained by natural selection acting alone, but the conditions for polymorphism maintenance by natural selection will usually be unrealistic for the case of microhabitat variation. Microhabitat variation and sexual selection for conspicuous males may thus provide a situation particularly favorable to the maintenance of male color polymorphisms. These results are important both because of the general insight they provide into a little appreciated mechanism for the maintenance of variation in natural populations and because such variation is an important prerequisite for sympatric speciation.     

Adaptive Role of Inversion Polymorphism of Drosophila subobscura in Lead Stressed Environment

Local adaptation to environmental stress at different levels of genetic polymorphism in various plants and animals has been documented through evolution of heavy metal tolerance. We used samples of Drosophila subobscura populations from two differently polluted environments to analyze the change of chromosomal inversion polymorphism as genetic marker during laboratory exposure to lead. Exposure to environmental contamination can affect the genetic content within a particular inversion and produce targets for selection in populations from different environments. The aims were to discover whether the inversion polymorphism is shaped by the local natural environments, and if lead as a selection pressure would cause adaptive divergence of two populations during the multigenerational laboratory experiment. The results showed that populations retain signatures from past contamination events, and that heavy metal pollution can cause adaptive changes in population. Differences in inversion polymorphism between the two populations increased over generations under lead contamination in the laboratory. The inversion polymorphism of population originating from the more polluted natural environment was more stable during the experiment, both under conditions with and without lead. Therefore, results showed that inversion polymorphism as a genetic marker reflects a strong signature of adaptation to the local environment, and that historical demographic events and selection are important for both prediction of evolutionary potential and long-term viability of natural populations.     

Neutrality tests of conservative-radical amino acid changes in nuclear- and mitochondrially-encoded proteins

The neutralist-selectionist debate should not be viewed as a dichotomy but as a continuum. While the strictly neutral model suggests a neutralist-selectionist dichotomy, the nearly neutral model is a continuous model spanning strict neutrality through weak selection (Ns approximately 1) to deterministic selection (Ns>3). We illustrate these points with polymorphism and divergence data from a sample of 73 genes (31 mitochondrial, 36 nuclear genes from Drosophila, and six Arabidopsis data sets). In an earlier study we used the McDonald-Kreitman (MK) test to show that amino acid replacement polymorphism in animal mitochondrial genes and Arabidopsis genes show a consistent trend toward negative selection, whereas nuclear genes from Drosophila span a range from negative selection, through neutrality, to positive selection. Here we analyze a subset of these genes (13 Drosophila nuclear, ten mitochondrial, and six Arabidopsis nuclear) for polymorphism and divergence of conservative and radical amino acid replacements (a protein-based conservative-radical MK, or pMK, test). The distinct patterns of selection between the different genomes is not apparent with the pMK test. Different definitions of conservative and radical (based on amino acid polarity, volume or charge) give inconsistent results across genes. We suggest that segregating fitness difference between silent and replacement mutations are more visible to selection than are segregating fitness differences between conservative and radical amino acid mutations. New data on the variation among genes with different opportunities for positive and negative selection are as important to the continuum view of the neutralist-selectionist debate as is the distribution of selection coefficients within individual genes.     

Selection at linked sites in the partial selfer Caenorhabditis elegans

Natural selection can produce a correlation between local recombination rates and levels of neutral DNA polymorphism as a consequence of genetic hitchhiking and background selection. Theory suggests that selection at linked sites should affect patterns of neutral variation in partially selfing populations more dramatically than in outcrossing populations. However, empirical investigations of selection at linked sites have focused primarily on outcrossing species. To assess the potential role of selection as a determinant of neutral polymorphism in the context of partial self-fertilization, we conducted a multivariate analysis of single-nucleotide polymorphism (SNP) density throughout the genome of the nematode Caenorhabditis elegans. We based the analysis on a published SNP data set and partitioned the genome into windows to calculate SNP densities, recombination rates, and gene densities across all six chromosomes. Our analyses identify a strong, positive correlation between recombination rate and neutral polymorphism (as estimated by noncoding SNP density) across the genome of C. elegans. Furthermore, we find that levels of neutral polymorphism are lower in gene-dense regions than in gene-poor regions in some analyses. Analyses incorporating local estimates of divergence between C. elegans and C. briggsae indicate that a mutational explanation alone is unlikely to explain the observed patterns. Consequently, we interpret these findings as evidence that natural selection shapes genome-wide patterns of neutral polymorphism in C. elegans. Our study provides the first demonstration of such an effect in a partially selfing animal. Explicit models of genetic hitchhiking and background selection can each adequately describe the relationship between recombination rate and SNP density, but only when they incorporate selfing rate. Clarification of the relative roles of genetic hitchhiking and background selection in C. elegans awaits the development of specific theoretical predictions that account for partial self-fertilization and biased sex ratios.     

Preferential mating in symmetric multilocus systems: stability conditions of the central equilibrium

Several multilocus models that incorporate both preferential mating and viability selection are studied. Specifically, a class of symmetric heterozygosity models are considered that assign individuals to phenotypic classes according to which loci are in heterozygous state regardless of the actual allelic content. Otherwise, an arbitrary number of loci, number of alleles per locus, and arbitrary recombination scheme, viability parameters and preferential mating pattern based on phenotypes are allowed. The conditions for the stability of a central polymorphism are indicated and interpreted. The effects of viability and preference selection may be summarized in a single quantity for each phenotypic class, a generalized fitness. Preferential assortative mating alone can produce stability for a central polymorphism as in the case of viability selection when sexual attractiveness or general fitness increases with higher levels of heterozygosity. The situation is more complex with sexual selection.     

The evolution of plumage polymorphism in birds of prey and owls: the apostatic selection hypothesis revisited

Co-evolution between phenotypic variation and other traits is of paramount importance for our understanding of the origin and maintenance of polymorphism in natural populations. We tested whether the evolution of plumage polymorphism in birds of prey and owls was supported by the apostatic selection hypothesis using ecological and life-history variables in birds of prey and owls and performing both cross taxa and independent contrast analyses. For both bird groups, we did not find any support for the apostatic selection hypothesis being the maintaining factor for the polymorphism: plumage polymorphism was not more common in taxa hunting avian or mammalian prey, nor in migratory species. In contrast, we found that polymorphism was related to variables such as sexual plumage dimorphism, population size and range size, as well as breeding altitude and breeding latitude. These results imply that the most likely evolutionary correlate of polymorphism in both bird groups is population size, different plumage morphs might simply arise in larger populations most likely because of a higher probability of mutations and then be maintained by sexual selection.     

Temporally varying selection on multiple alleles: A diffusion analysis

A generalization of Gillespie's SAS-CFF model for natural selection acting on multiple alleles in a randomly fluctuating environment is presented that relaxes symmetry assumptions concerning the variances and covariances of allelic effects. The stationary density for a multidimensional diffusion approximation of the model is obtained and provides approximate necessary and sufficient conditions for the existence of stable polymorphisms. These conditions have exactly the same form as those derived by Kimura and Mandel for polymorphism under multiple allele selection in a constant environment, except that the time-invariant fitnesses are replaced by the approximate geometric mean fitnesses of the genotypes over time. An example illustrates that this simple relationship between random environment and constant environment conditions for polymorphism does not hold for more general selection schemes. The implications of these results for the maintenance of multiple alleles by balancing selection are discussed.     

Heterozygote advantage and the maintenance of polymorphism for multilocus traits

Explaining how polymorphism is maintained in the face of selection remains a puzzle since selection tends to erode genetic variation. Provided an infinitely large unsubdivided population and no frequency-dependance of selective values, heterozygote advantage is the text book explanation for the maintenance of polymorphism when selection acts at a diallelic locus. Here, we investigate whether this remains true when selection acts at multiple diallelic loci. We use five different definitions of heterozygote advantage that largely cover this concept for multiple loci. Using extensive numerical simulations, we found no clear associations between the presence of any of the five definitions of heterozygote advantage and the maintenance of polymorphism at all loci. The strength of the association decreases as the number of loci increases or as recombination decreases. We conclude that heterozygote advantage cannot be a general mechanism for the maintenance of genetic polymorphism at multiple loci. These findings suggest that a correlation between the number of heterozygote loci and fitness is not warranted on theoretical ground.