Red Queen Hypothesis Research Articles

In Search of the Red Queen

The Red Queen hypothesis is about co-evolution, reciprocal adaptive genetic changes within populations of interacting species 1. Karieva P. Coevolutionary arms races: is victory possible?. Proc. Natl Acad. Sci. USA. 1999; 96: 8-10 Crossref PubMed Scopus (35) Google Scholar . The hypothesis (at least, in one of its guises) states that one possible outcome of co-evolution is endless selection for adaptation and counter-adaptation. It takes its name from Lewis Carroll's book ‘Through the Looking Glass’ in which the Red Queen explains to Alice that ‘here, you see, it takes all the running you can do, to keep in the same place’. The Red Queen hypothesis has been widely invoked to explain fundamental biological observations such as the existence of sex, the evolution of virulence and the maintenance of genetic polymorphisms. The hypothesis applies potentially to all kinds of species interactions, such as prey–predator or plant–herbivore, but here we shall focus on host–parasite interactions and polymorphisms in host susceptibility and parasite infectivity.

Host-parasite coevolution in a multilocus gene-for-gene system.

This paper examines a mathematical model for the coevolution of parasite virulence and host resistance under a multilocus gene-for-gene interaction. The degrees of parasite virulence and host resistance show coevolutionary cycles for sufficiently small costs of virulence and resistance. Besides these coevolutionary cycles of a longer period, multilocus genotype frequencies show complex fluctuations over shorter periods. All multilocus genotypes are maintained within host and parasite classes having the same number of resistant/virulent alleles and their frequencies fluctuate with approximately equally displaced phases. If either the cost of virulence or the number of resistance loci is larger then a threshold, the host maintains the static polymorphism of singly (or doubly or more, depending on the cost of resistance) resistant genotypes and the parasite remains universally avirulent. In other words, host polymorphism can prevent the invasion of any virulent strain in the parasite. Thus, although assuming an empirically common type of asymmetrical gene-for-gene interaction, both host and parasite populations can maintain polymorphism in each locus and retain complex fluctuations. Implications for the red queen hypothesis of the evolution of sex and the control of multiple drug resistance are discussed.

Parasite adaptation to locally common host genotypes

According to the Red Queen hypothesis--which states that interactions among species (such as hosts and parasites) lead to constant natural selection for adaptation and counter-adaptation--the disproportionate evolutionary success of parasites on common host genotypes leads to correlated selection for sexual reproduction and local adaptation by the parasite population. Here we determined whether local adaptation is due to disproportionate infection of common host genotypes, and, if so, whether infection of common host genotypes is due to commonness per se, or some other aspect of these genotypes. In a reciprocal cross-inoculation experiment parasites occupying the same geographical area (sympatric) infected locally common host genotypes significantly more often than rare host genotypes, whereas parasites occupying separate geographical areas (allopatric) showed no such significant difference. A mixed source of parasites (containing F1 hybrids) also showed no difference in infection between rare and common host genotypes. These results show that local adaptation results from parasite tracking of locally common host genotypes, and, as such, a necessary condition of the Red Queen hypothesis is met.

Why sex? A parody on the paradox

After decades of establishing concepts such as fitness, adaptation, and reproductive success on top of one another, a paradox quaked evolutionary theory in the early seventies (cf. Williams 1975: preface). Why should sex have evolved in the first place? Nature did not obey theory any more! Asexually reproducing organisms pass on 100% of their genetic information to their offspring, while sexually reproducing organisms inherit only 50%. is the two-fold advantage for asexual reproduction, and other obvious of sexual reproduction are apparent although harder to quantify. To find a sexual partner, mate, and reproduce successfully costs time and energy. And so does the often necessary courtship, when the genders need to overcome conflicting interests. So, while there should not have been a lot of sex in theory, it obviously was the dominant way of life among animals and plants. George C. Williams (1975: V) opened his seminal book on Sex and evolution with the proclamation of the crisis: This book is written in the conviction that the prevalence of sexual reproduction in higher plants and animals is inconsistent with current evolutionary theory. [... ] Many well informed readers may disagree with much of my reasoning, but I hope at least to convince them that there is a kind of crisis at hand in evolutionary biology. Since then, much research has been done and many models proffered to answer the question: Why is there sex? But instead of getting one straight answer more and more questions cropped up. Discriminating two different kinds of questions will be important in the following: 1) How much of a genome is reproduced and what advantage does this convey? 2) In which way is reproduction achieved and what advantage does this convey? Comparing reproductive units, like genes or organisms, while answering the first question leads to the paradox: 100% inheritance (asexual reproduction) will be of two-fold advantage compared to 50% (sexual reproduction), although sexuality is the prevalent mode of reproduction among animals and plants. The answers to the second question are manifold and complex, often involving models. As a general result, sexual reproduction has advantages under circumstances like intense sibling competition; an onslaught of diseases combined with vulnerability to parasites and other enemies; accumulation of detrimental mutations; or a saturated and heterogeneous environment (Stearns 1987). Asking in which way and under which circumstances reproduction is achieved, these models now have famous nicknames like Tangled Bank hypothesis, Red Queen hypothesis, or Miller's Ratchet. But while sexual reproduction will be favoured under these circumstances, nobody was able to cast this into a simple, quantitative advantage exceeding a two-fold ratio. And, like a jack-in-the-box, the original question jumped up again with ever new twists, whenever the paradox seemed to be put to rest: Why should sexual reproduction exist? How can its short-term disadvantage be overcome by its long-term advantage? Why do ancient asexual species, such as bdelloid rotifers and darwinulid ostracods persist, if asexuality was an evolutionary dead-end in the long run? If the benefits of sexuality could be obtained through facultative or temporary sex, why are most animal species obligatory and continually sexual? Why are asexual organelles within sexual cells, such as mitochondria and chloroplasts, not suffering from piling up mutation loads, parasitic DNA or intraclonal competition? Or why are they not taking over the sexual cells?

Simulated coevolution in a mutating ecology.

The bit-string Penna model is used to simulate the competition between an asexual parthenogenetic and a sexual population sharing the same environment. A newborn of either population can mutate and become a part of the other with some probability. In a stable environment the sexual population soon dies out. When an infestation by rapidly mutation genetically coupled parasites is introduced, however, sexual reproduction prevails, as predicted by the so-called Red Queen hypothesis for the evolution of sex.

Population structure, parasitism, and survivorship of sexual and autodiploid parthenogenetic Campeloma limum.

Two theories for the maintenance of sexual reproduction, the Red Queen hypothesis and mutation accumulation, suggest that the dispersal rates of sexuals and asexuals may determine the elimination or persistence of asexuals. Under higher dispersal rates of asexuals, asexuals may temporarily escape virulent parasites and reduce the effects of deleterious mutations. In the present study, I examine the population structure, parasite loads, and juvenile survivorship of Campeloma limum sexuals and autodiploid parthenogens from the southeastern U.S. Atlantic coastal plain. Using mtDNA sequence variation, it is shown that parthenogenetic haplotypes with limited sequence divergence are geographically widespread throughout this region and there is no significant population differentiation over a broad geographical scale. Sexual C. limum populations show significant mtDNA differentiation among and within river drainages and there is significant isolation by distance. These patterns are consistent with a recent origin and range expansion of parthenogens. Prevalence of infection by digenetic trematodes is significantly higher in autodiploid parthenogens, and the variance of prevalence is also higher in autodiploid parthenogens. I argue that the latter pattern indicates that unparasitized parthenogens have temporarily escaped these virulent parasites, but recolonization of these populations by trematodes results in high infection levels (> 40%), possibly due to reduced variation in resistance genes. I also examined whether the survivorship of juvenile sexuals and parthenogens varied under different stress levels. Sexual juveniles had twofold higher survivorship in all environments. Compared to polyploid parthenogens, autodiploid parthenogens may be less buffered against the effects of deleterious recessive alleles. I propose that the combined effects of higher parasitism and reduced juvenile survivorship of these autodiploid parthenogens accounts for the spatial distribution of sexual and parthenogenetic C. limum in the Atlantic coastal plain. Parthenogens may persist by higher dispersal rates into marginal habitats where there is a temporary escape from digenetic trematodes and competition with sexuals.

POPULATION STRUCTURE, PARASITISM, AND SURVIVORSHIP OF SEXUAL AND AUTODIPLOID PARTHENOGENETIC CAMPELOMA LIMUM

Two theories for the maintenance of sexual reproduction, the Red Queen hypothesis and mutation accumulation, suggest that the dispersal rates of sexuals and asexuals may determine the elimination or persistence of asexuals. Under higher dispersal rates of asexuals, asexuals may temporarily escape virulent parasites and reduce the effects of deleterious mutations. In the present study, I examine the population structure, parasite loads, and juvenile survivorship of Campeloma limum sexuals and autodiploid parthenogens from the southeastern U.S. Atlantic coastal plain. Using mtDNA sequence variation, it is shown that parthenogenetic haplotypes with limited sequence divergence are geographically widespread throughout this region and there is no significant population differentiation over a broad geographical scale. Sexual C. limum populations show significant mtDNA differentiation among and within river drainages and there is significant isolation by distance. These patterns are consistent with a recent origin and range expansion of parthenogens. Prevalence of infection by digenetic trematodes is significantly higher in autodiploid parthenogens, and the variance of prevalence is also higher in autodiploid parthenogens. I argue that the latter pattern indicates that unparasitized parthenogens have temporarily escaped these virulent parasites, but recolonization of these populations by trematodes results in high infection levels (> 40%), possibly due to reduced variation in resistance genes. I also examined whether the survivorship of juvenile sexuals and parthenogens varied under different stress levels. Sexual juveniles had twofold higher survivorship in all environments. Compared to polyploid parthenogens, autodiploid parthenogens may be less buffered against the effects of deleterious recessive alleles. I propose that the combined effects of higher parasitism and reduced juvenile survivorship of these autodiploid parthenogens accounts for the spatial distribution of sexual and parthenogenetic C. limum in the Atlantic coastal plain. Parthenogens may persist by higher dispersal rates into marginal habitats where there is a temporary escape from digenetic trematodes and competition with sexuals.Corresponding Editor: R. Burton

Pressions sélectives dans les systèmes parasites-hôtes

Selective pressures in host-parasite systems are the result of a continuous conflict between the divergent interests of each partner, on the long run. Whereas the fitness (lifetime reproductive success) of parasites is usually increased by a higher frequency of encounters with susceptible hosts and a better survival rate after infection, the fitness of hosts is increased by opposite processes, avoidance of encounters with infective stages and destruction of the parasites. These selective processes, often referred to as coevolution or arms races are in agreement with the Red Queen hypothesis of Van Valen, which assumes indefinite adaptive changes in both partners, in order to set up counter-measures against the weapons of "the other". Arms races in host-parasite systems thus suggest a gradualistic evolution, but this does not contradict the present day ideas on the tempo changes in the course of evolution (punctuated equilibria). Numerous factors, either genetic (evolutionary lag...), environmental (nutritional status...) or cultural (prevention, vaccination, therapy...) influence the severity of infections at an individual scale. The "terrain", which is a component of the individual phenotype, is thus at the cross-roads of genes, environment and culture. Humans must count more on their intelligence than on natural selection to prevent and cure infectious and parasitic diseases.

On Sex, Mate Selection and the Red Queen

The widespread occurrence of sexual reproduction despite the two-fold disadvantage of producing males, is still an unsolved mystery in evolutionary biology. One explanatory theory, called the “Red Queen” hypothesis, states that sex is an adaptation to escape from parasites. A more recent hypothesis, the mate selection hypothesis, assumes that non-random mating, possible only with sex, accelerates the evolution of beneficial traits. This paper tests these two hypotheses, using an agent-based or “micro-analytic” evolutionary algorithm where host–parasite interaction is simulated adhering to biological reality. While previous simpler models testing the “Red Queen” hypothesis considered mainly haploid hosts, stable population density, random mating and simplified expression of fitness, our more realistic model allows diploidy, mate selection, live history constraints and variable population densities. Results suggest that the Red Queen hypothesis is not valid for more realistic evolutionary scenarios and that each of the two hypotheses tested seem to explain partially but not exhaustively the adaptive value of sex. Based on the results we suggest that sexual populations in nature should avoid both, maximizing outbreeding or maximizing inbreeding and should acquire mate selection strategies which favour optimal ranges of genetic mixing in accordance with environmental challenges.

The Evolution of Mating Preferences and Major Histocompatibility Complex Genes.

House mice prefer mates genetically dissimilar at the major histocompatibility complex (MHC). The highly polymorphic MHC genes control immunological self/nonself recognition; therefore, this mating preference may function to provide "good genes" for an individual's offspring. However, the evidence for MHC-dependent mating preferences is controversial, and its function remains unclear. Here we provide a critical review of the studies on MHC-dependent mating preferences in mice, sheep, and humans and the possible functions of this behavior. There are three adaptive hypotheses for MHC-dependent mating preferences. First, MHC-disassortative mating preferences produce MHC-heterozygous offspring that may have enhanced immunocompetence. Although this hypothesis is not supported by tests of single parasites, MHC heterozygotes may be resistant to multiple parasites. Second, we propose that MHC-dependent mating preferences enable hosts to provide a "moving target" against rapidly evolving parasites that escape immune recognition (the Red Queen hypothesis). Such parasites are suspected to drive MHC diversity through rare-allele advantage. Thus, the two forms of parasite-mediated selection thought to drive MHC diversity, heterozygote and rare-allele advantage, will also favor MHC-dependent mating preferences. Finally, MHC-dependent mating preferences may also function to avoid inbreeding; a hypothesis consistent with other evidence that MHC genes play a role in kin recognition.

HOST-PARASITE COEVOLUTION: EVIDENCE FOR RARE ADVANTAGE AND TIME-LAGGED SELECTION IN A NATURAL POPULATION.

In theory, parasites can create time-lagged, frequency-dependent selection in their hosts, resulting in oscillatory gene-frequency dynamics in both the host and the parasite (the Red Queen hypothesis). However, oscillatory dynamics have not been observed in natural populations. In the present study, we evaluated the dynamics of asexual clones of a New Zealand snail, Potamopyrgus antipodarum, and its trematode parasites over a five-year period. During the summer of each year, we determined host-clone frequencies in random samples of the snail to track genetic changes in the snail population. Similarly, we monitored changes in the parasite population, focusing on the dominant parasite, Microphallus sp., by calculating the frequency of clones in samples of infected individuals from the same collections. We then compared these results to the results of a computer model that was designed to examine clone frequency dynamics for various levels of parasite virulence. Consistent with these simulations and with ideas regarding dynamic coevolution, parasites responded to common clones in a time-lagged fashion. Finally, in a laboratory experiment, we found that clones that had been rare during the previous five years were significantly less infectible by Microphallus when compared to the common clones. Taken together, these results confirm that rare host genotypes are more likely to escape infection by parasites; they also show that host-parasite interactions produce, in a natural population, some of the dynamics anticipated by the Red Queen hypothesis.

THE MAINTENANCE OF SEX BY PARASITISM AND MUTATION ACCUMULATION UNDER EPISTATIC FITNESS FUNCTIONS.

The mutation accumulation hypothesis predicts that sex functions to reduce the population mutational load, while the Red Queen hypothesis holds that sex is adaptive as a defense against coevolving pathogens. We used computer simulations to examine the combined and separate effects of selection against deleterious mutations and host-parasite coevolution on the spread of a clone into an outcrossing sexual population. The results suggest that the two processes operating simultaneously may select for sex independent of the exact shape of the function that maps mutation number onto host fitness.

Isolation from an Ant Myrmecia gulosa of Two Inducible O-Glycosylated Proline-rich Antibacterial Peptides

Reported here is the isolation and characterization of two antibacterial peptides synthesized in an ant Myrmecia gulosa in response to bacterial challenge. The peptides were purified by reversed-phase high performance liquid chromatography and characterized by peptide sequencing and mass spectrometry. Both peptides were formed from 16 amino acids, were rich in proline ( approximately 30%), and had N-acetylgalactosamine O-linked to a conserved threonine. The activity of a synthetic non-glycosylated isoform was markedly reduced demonstrating that glycosylation was necessary for maximum activity. The peptides were active only against growing Escherichia coli. They were inactive against stationary cells, Gram-positive bacteria, the yeast Candida albicans, two species of mammalian cells, and bovine pestivirus.

Lymphocyte survival: a red queen hypothesis.

A pool of immune cells lies apparently dormant in the body, ready to become activated if awakened by a foreign antigen. In a Perspective Freitas and Rocha discuss the new finding (reported on page 1986 of this issue) that in fact these cells are waiting quite actively, kept in a receptive state by the presence of a transcription factor, LKLF.

FREQUENCY-DEPENDENT SELECTION IN A MAMMALIAN RNA VIRUS.

RNA viruses have been used as experimental systems to test evolutionary hypotheses such as Muller's ratchet (Chao 1990; Duarte et al. 1992, 1993; Clarke et al. 1993), the Red Queen hypothesis (Clarke et al. 1994), the nature of the adaptive topography (Elena, 1995; Elena et al. 1996), and the dynamics of adaptive evolution (Elena 1995; Novella et al. 1995). Two hypotheses which have received attention in virus studies are the competitive exclusion principle and frequency-dependent selection. The competitive exclusion principle (Hardin 1960) states that two populations or species competing for the same limiting resource cannot stably coexist because one competitor will displace the other. An exception to the competitive exclusion principle can occur under frequency-dependent selection, in which it is possible to find a frequency at which two populations may coexist stably and indefinitely despite the fact that they are competing for the same resource (Ayala and Campbell 1974). Frequency-dependent selection has been demonstrated to occur in organisms as different as Drosophila (Wright and Dobzhansky 1946; Ayala 1971; Kojima 1971; Van Delden et al. 1978) and Escherichia coli (Helling et al. 1987; Chao et al. 1977; Lenski and Hattingh 1986; Turner et al. 1996) among others. Evidence for the applicability of the competitive exclusion principle to viruses has been reported by Clarke et al. (1994) in their work with vesicular stomatitis virus (VSV). These authors observed that two virus populations of approximately equal fitness can coexist during prolonged replication in the same stable environment; but stochastic changes in the population balance did eventually occur, and their impact on the competition was sudden and decisive. They justified their observations by the stochastic fixation of highly advantageous or deleterious mutations in variants of one of the two competing populations. One alternative explanation for the Clarke et al. (1994) observations is the absence of any stable coexistence equilibrium points. The clear and simple objective of the present paper was to determine if frequency-dependent selection acting on viral populations can promote the stable coexistence of two genotypes competing for the same resource.

Reproducible Nonlinear Population Dynamics and Critical Points During Replicative Competitions of RNA Virus Quasispecies

RNA virus evolution is generally considered to be highly unpredictable, but tests of determinism in the evolution of competing populations during viral infections have not been performed. Here we study the fate of two closely related evolving quasispecies of vesicular stomatitis virus, by determining the relative concentration of a wild-type clone and a surrogate marked virus subclone (MARM-C) upon extensive competitive replication in a constant cell culture environment. A highly predictable nonlinear behaviour of the two competing populations was found. In addition, the presence of critical points, which are defined as points from which viral competitions may follow different trajectories, has been documented. Critical points were reached after nearly constant periods of time. The dynamics of relative fitness values for both competing populations were calculated during the replication passages. Concomitant with expected fitness gain of both competing viral populations (which follow the Red Queen hypothesis) a tendency for the MARM-C to gain less fitness than the wild-type was observed. Although fitness variations were noisy, this tendency was seen in all evolutionary replicas. Thus, despite the stochastic process of mutation that leads to a continuous generation of mutant genomes during RNA virus replication, a nonlinear, nearly deterministic evolutionary behaviour has been observed. It is proposed that such a behaviour is mediated by a low-pass filter (averaging of mutational noise signals) due to competitive selection among variants.

The Red Queen Hypothesis and plant/pathogen interactions.

The Red Queen Hypothesis (RQH) explains how pathogens may maintain sexual reproduction in hosts. It assumes that parasites become specialized on common host genotypes, reducing their fitness. Such frequency-dependent selection favors sexual reproduction in host populations. Necessary conditions are that resistance and virulence are genotype specific so that host genotype frequencies respond to changes in pathogen genotype frequencies, and vice versa. Empirical evidence on the genetic basis of disease, variation in resistance and virulence, and patterns of infection in sexual and asexual plants support certain features of the hypothesis. However, gene-for-gene interactions are generally not consistent with the RQH because they do not result in cycling of gene frequencies, unlike a matching allele mechanism. A conclusion of whether the RQH can explain the maintenance of sexual reproduction cannot be reached at present. Nevertheless, the RQH theory has shed light on many aspects of plant/pathogen interactions important for reducing pathogen damage in agricultural systems.

Evolution and Stasis in Plant‐‐Pathogen Associations

The impact of disease on plant populations may change as a result of coevolutionary interactions. The Red Queen hypothesis suggests that parasites provide a selective advantage to host sexual recombination sufficient to explain it persistence despite the twofold advantage of asexual reproduction. The constant production of resistant host genotypes by sexual recombination favors parasite genotypes that can overcome host resistance, resulting in a coevolutionary arms race. Systemic fungal parasites differ from nonsystemic fungi in ways that affect plant—pathogen interactions. Many systemic fungal parasites castrate their host plants, which reduces the potential for production of genetically variable, resistant progeny. Moreover, host genotypes susceptible to infection by the maternal pathogen are perpetuated through parasite—induced asexual reproduction or enforced selfing. Grasses in the genus Danthonia infected by Atkinsonella hypoxylon represent a model system for investigating evolution and stasis in plant—pathogen associations. Infected plants, unlike uninfected plants, reproduce only by self—fertilized seed through which the fungus is vertically transmitted. Other similar associations exist, suggesting that parasites can often enforce genetic uniformity within host populations.

Basic concepts in RNA virus evolution

A hallmark of RNA genomes is the error-prone nature of their replication and retrotranscription. The major biochemical basis of the limited replication fidelity is the absence of proofreading/repair and postreplicative error correction mechanisms that normally operate during replication of cellular DNA. In spite of this unique feature of RNA replicons, the dynamics of viral populations seems to follow the same basic principles that classical population genetics has established for higher organisms. Here we review recent evidence of the profound effects that genetic bottlenecks have in enhancing the deleterious effects of Muller's ratchet during RNA virus evolution. The validity of the Red Queen hypothesis and of the competitive exclusion principle for RNA viruses are viewed as the expected result of the highly variable and adaptable nature of viral quasispecies. Viral fitness, or ability to replicate infectious progeny, can vary a million-fold within short time intervals. Paradoxically, functional and structural studies suggest extreme limitations to virus variation. Adaptability of RNA viruses appears to be based on the occupation of very narrow portions of sequence space at any given time.

PARASITES, SEX, AND EARLY REPRODUCTION IN A MIXED POPULATION OF FRESHWATER SNAILS.

Two hypotheses have been presented regarding the effects of parasites on the life-history evolution of their hosts. First, a high risk of infection should favor sexual reproduction over parthenogenetic reproduction, because sexually produced progeny should be better able to evade coevolving parasites (Levin 1975; Jaenike 1978; Hamilton 1980; Bell 1982; Hamilton et al. 1990; Howard and Lively 1994); this idea has come to be known as the Red Queen hypothesis (see Bell 1982). Second, a high risk of infection is predicted to favor early reproduction, especially if infection results in host castration or death (Gadgil and Bossert 1970; Law 1979; Michod 1979; Minchella and Loverde 1981). The evidence from comparative studies have been generally favorable to both the Red Queen hypotheses (Lively 1987, 1992; Schrag et al. 1994) and to the predictions of life-history theory (Lafferty 1993). These studies have focused on comparing data from different populations of aquatic gastropods. In the present study, we examined the predictions of these theories in a single population of freshwater snails (Potamopyrgus antipodarum), which contains a mixture of obligately sexual and obligately parthenogenetic females. The results were in agreement with both theories.