Negative frequency-dependent selection on polymorphic color morphs in adders

It is intriguing that conspicuous colour morphs of a prey species may be maintained at low frequencies alongside cryptic morphs. Negative frequency-dependent selection by predators using search images (‘apostatic selection’) is often suggested without rejecting alternative explanations. Using a maximum likelihood approach we fitted predictions from models of genetic drift, migration, constant selection, heterozygote advantage or negative frequency-dependent selection to time-series data of colour frequencies in isolated populations of a marine snail (Littorina saxatilis), re-established with perturbed colour morph frequencies and followed for >20 generations. Snails of conspicuous colours (white, red, banded) are naturally rare in the study area (usually <10%) but frequencies were manipulated to levels of ~50% (one colour per population) in 8 populations at the start of the experiment in 1992. In 2013, frequencies had declined to ~15–45%. Drift alone could not explain these changes. Migration could not be rejected in any population, but required rates much higher than those recorded. Directional selection was rejected in three populations in favour of balancing selection. Heterozygote advantage and negative frequency-dependent selection could not be distinguished statistically, although overall the results favoured the latter. Populations varied idiosyncratically as mild or variable colour selection (3–11%) interacted with demographic stochasticity, and the overall conclusion was that multiple mechanisms may contribute to maintaining the polymorphisms.

Negative frequency-dependent selection among species is a key driver of community diversity in natural systems, but the degree to which negative frequency-dependent selection shapes patterns of survival and genetic diversity within species is poorly understood. In a 5-year field experiment, we show that seedlings of a tropical palm with rare genotypes had a pronounced survival advantage over seedlings with common genotypes, with effect sizes comparable to that of light availability. This 'rare genotype advantage' led to an increase in population-wide genetic diversity among seedlings compared to null expectations, as predicted by negative frequency-dependent selection, and increased reproductive success in adult trees with rare genotypes. These results suggest that within-species negative frequency-dependent selection of genotypes can shape genetic variation on ecologically relevant timescales in natural systems and may be a key, overlooked source of non-random mortality for tropical plants.

Frequency-dependent selection is theoretically predicted to have an important impact on predator–prey dynamics, but little is understood about this process in nature. We investigated oak–squirrel interactions to test the hypothesis that tree squirrels predate/disperse white oak acorns based on the frequency of their germination phenotypes (dormancy, i.e., delayed germination vs. nondormancy, i.e., immediately germinating), which in turn influences dispersal and establishment of these oaks. In Central China, we manipulated the relative frequency of dormant and nondormant acorns available to Père David's Rock squirrel (Sciurotamias davidianus) with 2 white oaks (QAA, Quercus aliena var. acutesevata and QSB, Quercus serrata var. breviptiolata) that exhibit considerable variation in acorn germination between and within oak species throughout the fruiting season. We predicted that dispersal success (i.e., the probability of a viable acorn being hoarded) of each germination phenotype would vary with the phenotype frequency and hence show either positive or negative frequency-dependent selection. We found that acorn-embryo removal by squirrels may select for the dormant phenotype but is more likely to occur for early germinating acorns. We also found that both absolute and relative dispersal success of each germination phenotype increased with their frequency in the 2 white oaks, thus demonstrating positive frequency-dependent selection. Our results reveal that the frequency of germination phenotypes can account for as much as 40.5% and 21.4% of the observed dispersal success in QAA and QSB, respectively. We show that behavioral preferences of scatter-hoarding animals could result in frequency-dependent selection in nature, and such selection may help maintain variation in germination phenotypes in prey species.

Accounting for the abundance of genetic variation in the face of natural selection remains a central problem of evolutionary biology. Genetic polymorphisms are constantly arising through mutation, and although most are promptly eliminated, polymorphisms in functionally important traits are common. One mechanism that can maintain polymorphisms is negative frequency-dependent selection on alternative alleles, whereby the fitness of each decreases as its frequency increases. Examples of frequency-dependent selection are rare, especially when attempting to describe the genetic basis of the phenotype under selection. Here we show frequency-dependent selection in a well-known natural genetic polymorphism affecting fruitfly foraging behaviour. When raised in low nutrient conditions, both of the naturally occurring alleles of the foraging gene (for(s) and for(R)) have their highest fitness when rare-the hallmark of negative frequency-dependent selection. This effect disappears at higher resources levels, demonstrating the role of larval competition. We are able to confirm the involvement of the foraging gene by showing that a sitter-like mutant allele on a rover background has similar frequency-dependent fitness as the natural sitter allele. Our study represents a clear demonstration of frequency-dependent selection, and we are able to attribute this effect to a single, naturally polymorphic gene known to affect behaviour.

Negative frequency-dependent selection (NFDS) is one of the most powerful selective forces maintaining genetic polymorphisms in nature. Recently many prospective cases of polymorphisms by NFDS have been reported. Some of them are very complicated, although strongly supportive of the NFDS. Here we investigate NFDS in wild populations of the dimorphic damselfly Ischnura senegalensis, in which females occur as andromorphs and gynomorphs. Specifically, we (1) test fitness responses to morph frequencies, (2) built a simple population genetic model, and (3) compare the observed and predicted morph-frequency dynamics. Fitnesses of the two morphs are an inverse function of its own frequency in a population, and are about equal when their frequencies are similar. Thus the conditions necessary for NFDS are satisfied. The long-term field surveys show that the morph frequencies oscillate with a period of two generations. Morph frequencies in a small population undergo large oscillations whereas those in a large population do small oscillations. The demographic properties of the observed dynamics agree well with those of our model. This example is one of the simplest confirmed cases of NFDS maintaining genetic polymorphisms in nature.

Positive selection on a new beneficial mutation generates a characteristic pattern of DNA sequence polymorphism when it reaches an intermediate allele frequency. On genome sequences of African Drosophila melanogaster, we detected such signatures of selection at 37 candidate loci and identified “sweeping haplotypes (SHs)” that are increasing or have increased rapidly in frequency due to hitchhiking. Based on geographic distribution of SH frequencies, we could infer whether selective sweeps occurred starting from de novo beneficial mutants under simple constant selective pressure. Single SHs were identified at more than half of loci. However, at many other loci, we observed multiple independent SHs, implying soft selective sweeps due to a high beneficial mutation rate or parallel evolution across space. Interestingly, SH frequencies were intermediate across multiple populations at about a quarter of the loci despite relatively low migration rates inferred between African populations. This invokes a certain form of frequency-dependent selection such as heterozygote advantage. At one locus, we observed a complex pattern of multiple independent that was compatible with recurrent frequency-dependent positive selection on new variants. In conclusion, genomic patterns of positive selection are very diverse, with equal contributions of hard and soft sweeps and a surprisingly large proportion of frequency-dependent selection in D. melanogaster populations.

Loci subject to negative frequency-dependent selection are expected to exhibit higher effective migration rates compared to reference loci. Although the number of gene copies transferred between populations by migration is the same for all genes, those subject to negative frequency-dependent selection are more likely to be retained in the immigrant population because rare alleles are selectively favored. So far, evidence for this prediction has been indirect, based on summary statistics rather than on migration rate estimates. Here, we introduce an approximate Bayesian procedure to jointly estimate migration rates at two predefined sets of loci between two populations. We applied the procedure to compare migration rate estimates at the self-incompatibility locus (S-locus) with that at 10 reference loci in two plant species, Leavenworthia alabamica and L. crassa (Brassicaceae). The maximum likelihood estimate for the proportion of migrants (m) was four times higher at the S-locus than at reference loci, but the difference was not statistically significant. Lack of significance might be due to insufficient data, but perhaps also to the recent divergence of the two species (311 ka), because we also show using simulations that the effective migration rate at the S-locus is expected to increase with increasing divergence time. These findings aid in understanding the evolutionary dynamics of negative frequency-dependent selection and they suggest that divergence time should be accounted for when employing migration rates to help detect negative frequency-dependent selection.

Frequency-dependent disease impacts may contribute to the maintenance of genetic diversity and sexual reproduction in plant populations. In earlier work with experimental wheat (Triticum aestivum) populations at a single density, we found that stripe rust (caused by Puccinia striiformis) created frequency-dependent selection on its host but competitive interactions between host genotypes reduced the potential for disease to maintain genetic polymorphisms in this highly self-pollinated species; the weaker competitor actually exhibited positive disease-mediated frequency-dependent selection. Based on these results we predicted that at low density, where the overall level of competition is lower, disease would have a stronger impact relative to competition and thus be more likely to maintain genetic polymorphisms; at low densities the greatest effect of disease for negative frequency-dependent selection should be seen in the weak competitor. Here we report on results with wheat stripe rust in which we altered both the frequency and density of host genotypes in factorial combinations of two-way mixtures where each host genotype was attacked by its own specialized race of rust. Within each density disease levels increased with genotype frequencies, creating frequency-dependent disease attack at all densities. Similarly, disease created negative frequency-dependent selection on its host at all densities, as a genotype’s fitness was often greater at low than high frequency when disease was present. Disease levels increased with plant density in 1997 but decreased in 1998. While increasing plant density reduced absolute fitness, presumably as a result of increased competition, a genetic polymorphism was not more likely to be maintained at low than high density as we had predicted. Within each density, the impact of disease was insufficient to reverse the slope of the relationship between absolute fitness and planted frequency from positive to negative for the less competitive host genotype, thus preventing the maintenance of a genetic polymorphism.

Reciprocal transplant experiments have been used to estimate the probability that negative frequency-dependent selection by natural enemies has occurred in host populations by determining whether pest populations are less adapted to "foreign" (rare) hosts, which originate from a population with which the pests have not coevolved. However, these experiments usually confound the effects of frequency and origin: the rare genotypes are also genotypes that did not originate at a site. When clonal organisms are used, and the clones occur in more than one population, it is possible to separate the effects of origin and frequency. Here I present the results of an experiment in which Arabis clones of known frequency were reciprocally transplanted among sites. Contrary to expectations, clones at their site of origin had less disease, less herbivory, and higher fitness than foreign clones. However, variation within and among sites in herbivory and infection was large, suggesting that the number of sites and clones needed to thoroughly test the hypothesis of negative frequency-dependent selection in this system is very large: thus, these results are suggestive but not conclusive.

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking pre-existing niches, whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mutation. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the temporal trend in the speciation rate can also be explained by frequency-dependent selection. We construct a frequency-dependent and DNA sequence-based model of speciation. We compare our model to empirical diversity patterns observed for cichlid fish and Darwin's finches, two classic systems for which speciation rates and richness data exist. Negative frequency-dependent selection predicts well both the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity may be driven by incipient species abundance with frequency-dependent selection. Our results demonstrate that genetic-distance-based speciation and frequency-dependent selection are sufficient to explain the high diversity observed in natural systems and, importantly, predict decay through time in speciation rate in the absence of pre-existing niches.

Evolution favours the body form best adapted to the local environment, but it can also favour rare forms. Stickleback experiments reveal how these two selection forces can interact, and how this can limit population divergence. See Letter p.285 Natural selection nudges populations in different environments to diverge. This is divergent selection (DS). But there is also negative frequency-dependent selection (NFDS), which means that in certain circumstances rare varieties in a population will have a selective advantage. For example, in a large population of frogs, any frog that's actually a prince will get a lot of attention. DS and NFDS are rarely studied together as they occur on different spatial and temporal scales. Whereas DS describes the broad sweep of selection over generations, NFDS concerns the minutiae of, for example, mate choice. However, NFDS can be stronger than—and even oppose—divergent selection. Daniel Bolnick and William Stutz demonstrate this effect in populations of a freshwater fish—the three-spine stickleback. By transplanting lake-bred sticklebacks into streams, and vice-versa, they found that immigrants did much better than expected, provided that they were few in number, and constrained divergent selection.

Streptococcus pneumoniae can be divided into many strains, each a distinct set of isolates sharing similar core and accessory genomes, which co-circulate within the same hosts. Previous analyses suggested the short-term vaccine-associated dynamics of S. pneumoniae strains may be mediated through multi-locus negative frequency-dependent selection (NFDS), which maintains accessory loci at equilibrium frequencies. Long-term simulations demonstrated NFDS stabilised clonally-evolving multi-strain populations through preventing the loss of variation through drift, based on polymorphism frequencies, pairwise genetic distances and phylogenies. However, allowing symmetrical recombination between isolates evolving under multi-locus NFDS generated unstructured populations of diverse genotypes. Replication of the observed data improved when multi-locus NFDS was combined with recombination that was instead asymmetrical, favouring deletion of accessory loci over insertion. This combination separated populations into strains through outbreeding depression, resulting from recombinants with reduced accessory genomes having lower fitness than their parental genotypes. Although simplistic modelling of recombination likely limited these simulations’ ability to maintain some properties of genomic data as accurately as those lacking recombination, the combination of asymmetrical recombination and multi-locus NFDS could restore multi-strain population structures from randomised initial populations. As many bacteria inhibit insertions into their chromosomes, this combination may commonly underlie the co-existence of strains within a niche.

RECENT development in population genetics indicate that it is often misleading to treat selective values as constants1–5. These studies indicate that selective forces may be a function of genotype frequencies (frequency-dependent selection). For example, if the rarest genotype is most fit then the rare allele will increase in frequency but will not become fixed in the population, because as it gets more common the fitness of its carriers decreases. This mechanism is attractive since it leads to a stable gene frequency equilibrium which may not involve problems of genetic load or inbreeding depression. Experimental evidence has been obtained6,7 which supports the view that frequency dependence is involved in the maintenance of the esterase-6 (Est-6) and alcohol dehydrogenase (Adh) loci in Drosophila melanogaster. However, these results are subject to two major criticisms8–11. First, the observed frequency dependence may have resulted from poor experimental design. In the original report6 fitness estimates were made by comparisons of adult frequencies with those expected from the gene frequencies in the previous generation. Frequency-dependent selection appears as an artefact of this method12. Second, since inbred lines were used in these studies problems of linkage disequilibrium may have occurred. If this view is correct then the observed selective differences were due to differences between lines, not to differences between alleles at a locus. As a consequence of these criticisms the role of frequency dependence as a force responsible for maintaining enzyme polymorphism has been disputed9. The experiments reported here overcome these criticisms and indicate that frequency-dependent selection should be reconsidered as an important mechanism involved in the maintenance of enzyme polymorphism.

Negative frequency-dependent selection exerted by parasites and pathogens can generate a selective advantage for rare host genotypes. This mechanism, known as the Red Queen, is currently considered to be one of the most likely explanations for the predominance of sexual reproduction in natural populations. Even so, the extent to which the Red Queen can and does provide an advantage to sex in nature is fiercely debated. Here, we survey the history of the development of the Red Queen hypothesis as applied to the maintenance of sex and discuss its theoretical underpinnings. We then review and synthesize the current body of theory and empirical data relevant to assessing whether Red Queen dynamics are likely to contribute to any general explanation for why sex is so common. We conclude that while there are many independent lines of evidence in support of a role for the Red Queen, important theoretical and empirical gaps remain. In particular, there is a need for theory addressing the breadth of conditions under which the Red Queen can favor sex, predictions for the patterns of molecular evolution expected for loci under negative frequency-dependent selection, and empirical research evaluating the strength of parasite-mediated selection in nature and the genetics of susceptibility and infection.

Research on guppies provides the most definitive evidence yet for the rare-male effect — a long-standing hypothesis to explain the perplexing maintenance of variation in traits that are subject to strong mate choice. See Letter p.108 Given that natural selection is both ubiquitous and remorseless, how is it that variation is maintained in populations? This pressing question in evolutionary biology is answered by Kimberly Hughes and colleagues in a study of guppies (Poecilia reticulata), a particularly useful model system because guppy male colouration is one of the most genetically variable organismal traits known. It was shown previously that in a population of brightly coloured guppies, males with rare colour patterns tend to thrive, against expectation. Hughes et al. show, using carefully controlled wild populations, not only that female guppies prefer to mate with these rare males, but that the males produce more offspring than those of more common stripe. This phenomenon, known as negative frequency-dependent selection, shows that there is a price on exclusivity and provides a mechanism for maintaining variation in a population.