The coevolution of parasites with host-acquired immunity and the evolution of sex

Abstract. Here I present a deterministic model of the coevolution of parasites with the acquired immunity of their hosts, a system in which coevolutionary oscillations can be maintained. These dynamics can confer an advantage to sexual reproduction within the parasite population, but the effect is not strong enough to outweigh the twofold cost of sex. The advantage arises primarily because sexual reproduction impedes the response to fluctuating epistasis and not because it facilitates the response to directional selection—in fact, sexual reproduction often slows the response to directional selection. Where the cost of sexual reproduction is small, a polymorphism can be maintained between the sexuals and the asexuals. A polymorphism is maintained in which the advantage gained due to recombination is balanced by the cost of sex. At much higher costs of sex, a polymorphism between the asexual and sexual populations can still be maintained if the asexuals do not have a full complement of genotypes available to them, because the asexuals only outcompete those sexuals with which they share the same selected alleles. However, over time we might expect the asexuals to amass the full array of genotypes, thus permanently eliminating sexuals from the population. The sexuals may avoid this fate if the parasite population is finite. Although the model presented here describes the coevolution of parasites with the acquired immune responses of their hosts, it can be compared with other host-parasite models that have more traditionally been used to investigate Red Queen theories of the evolution of sex.     

Mitotic recombination counteracts the benefits of genetic segregation

The ubiquity of sexual reproduction despite its cost has lead to an extensive body of research on the evolution and maintenance of sexual reproduction. Previous work has suggested that sexual reproduction can substantially speed up the rate of adaptation in diploid populations, because sexual populations are able to produce the fittest homozygous genotype by segregation and mating of heterozygous individuals. In contrast, asexual populations must wait for two rare mutational events, one producing a heterozygous carrier and the second converting a heterozygous to a homozygous carrier, before a beneficial mutation can become fixed. By avoiding this additional waiting time, it was shown that the benefits of segregation could overcome a twofold cost of sex. This previous result ignores mitotic recombination (MR), however. Here, we show that MR significantly hastens the spread of beneficial mutations in asexual populations. Indeed, given empirical data on MR, we find that adaptation in asexual populations proceeds as fast as that in sexual populations, especially when beneficial alleles are partially recessive. We conclude that asexual populations can gain most of the benefit of segregation through MR while avoiding the costs associated with sexual reproduction.     

Male offspring production by asexual Potamopyrgus antipodarum, a New Zealand snail

As only females contribute directly to population growth, sexual females investing equally in sons and daughters experience a two-fold cost relative to asexuals producing only daughters. Typically, researchers have focused on benefits of sex that can counter this 'cost of males' and thus explain its predominance. Here, we instead ask whether asexuals might also pay a cost of males by quantifying the rate of son production in 45 experimental populations ('lineages') founded by obligately asexual female Potamopyrgus antipodarum. This New Zealand snail is a powerful model for studying sex because phenotypically similar sexual and asexual forms often coexist, allowing direct comparisons between sexuals and asexuals. After 2 years of culture, 23 of the 45 lineages had produced males, demonstrating that asexual P. antipodarum can make sons. We used maximum-likelihood analysis of a model of male production in which only some lineages can produce males to estimate that ~50% of lineages have the ability to produce males and that ~5% of the offspring of male-producing lineages are male. Lineages producing males in the first year of the experiment were more likely to make males in the second, suggesting that some asexual lineages might pay a cost of males relative to other asexual lineages. Finally, we used a simple deterministic model of population dynamics to evaluate how male production affects the rate of invasion of an asexual lineage into a sexual population, and found that the estimated rate of male production by asexual P. antipodarum is too low to influence invasion dynamics.     

Parasites and sexual reproduction in psychid moths

Persistence of sexual reproduction among coexisting asexual competitors has been a major paradox in evolutionary biology. The number of empirical studies is still very limited, as few systems with coexisting sexual and strictly asexual lineages have been found. We studied the ecological mechanisms behind the simultaneous coexistence of a sexually and an asexually reproducing closely related species of psychid moth in Central Finland between 1999 and 2001. The two species compete for the same resources and are often infected by the same hymenopteran parasitoids. They are extremely morphologically and behaviorally similar and can be separated only by their reproductive strategy (sexual vs. asexual) or by genetic markers. We compared the life-history traits of these species in two locations where they coexist to test predictions of the cost-of-sex hypothesis. We did not find any difference in female size, number of larvae, or offspring survival between the sexuals and asexuals, indicating that sexuals are subject to cost of sex. We also used genetic markers to check and exclude the possibility of Wolbachia bacteria infection inducing parthenogenesis. None of the samples was infected by Wolbachia and, thus, it is unlikely that these bacteria could affect our results. We sampled 38 locations to study the prevalence of parasitoids and the moths' reproductive strategy. We found a strong positive correlation between prevalence of sexual reproduction and prevalence of parasitoids. In locations where parasitoids are rare asexuals exist in high densities, whereas in locations with a high parasitoid load the sexual species was dominant. Spatial distribution alone does not explain the results. We suggest that the parasite hypothesis for sex may offer an explanation for the persistence of sexual moths in this system.     

Existence of two sexual races in the planarian species switching between asexual and sexual reproduction

In certain planarian species that are able to switch between asexual and sexual reproduction, determining whether a sexual has the ability to switch to the asexual state is problematic, which renders the definition of sexuals controversial. We experimentally show the existence of two sexual races, acquired and innate, in the planarian Dugesia ryukyuensis. Acquired sexuals used in this study were experimentally switched from asexuals. Inbreeding of acquired sexuals produced both innate sexuals and asexuals, but inbreeding of innate sexuals produced innate sexuals only and no asexuals. Acquired sexuals, but not innate sexuals, were forced to become asexuals by ablation and regeneration (asexual induction). This suggests that acquired sexuals somehow retain asexual potential, while innate sexuals do not. We also found that acquired sexuals have the potential to develop hyperplastic and supernumerary ovaries, while innate sexuals do not. In this regard, acquired sexuals were more prolific than innate sexuals. The differences between acquired and innate sexuals will provide a structure for examining the mechanism underlying asexual and sexual reproduction in planarians.     

Parasites in sexual and asexual mollies (Poecilia, Poeciliidae, Teleostei): a case for the Red Queen?

The maintenance of sexual reproduction in the face of its supposed costs is a major paradox in evolutionary biology. The Red Queen hypothesis, which states that sex is an adaptation to fast-evolving parasites, is currently one of the most recognized explanations for the ubiquity of sex and predicts that asexual lineages should suffer from a higher parasite load if they coexist with closely related sexuals. We tested this prediction using four populations of the sexual fish species Poecilia latipinna and its asexual relative Poecilia formosa. Contrary to expectation, no differences in parasite load could be detected between the two species.     

VARIATION IN THE STRENGTH OF MALE MATE CHOICE ALLOWS LONG‐TERM COEXISTENCE OF SPERM‐DEPENDENT ASEXUALS AND THEIR SEXUAL HOSTS

In several asexual taxa, reproduction requires mating with related sexual species to stimulate egg development, even though genetic material is not incorporated from the sexuals (gynogenesis). In cases in which gynogens do not invest in male function, they can potentially have a twofold competitive advantage over sexuals because the asexuals avoid the cost of producing males. If unmitigated, however, the competitive success of the asexuals would ultimately lead to their own demise, following the extinction of the sexual species that stimulate egg development. We have studied a model of mate choice among sexual individuals and asexual gynogens, where males of the sexual species preferentially mate with sexual females over gynogenetic females, to determine if such mating preferences can stably maintain both gynogenetic and sexual individuals within a community. Our model shows that stable coexistence of gynogens and their sexual hosts can occur when there is variation among males in the degree of preference for mating with sexual females and when pickier males pay a higher cost of preference.     

The effects of sex and mutation rate on adaptation in test tubes and to mouse hosts by Saccharomyces cerevisiae

Some hypotheses for the evolution of sex focus on adaptation to changing or heterogeneous environments, but these hypotheses have rarely been tested. We tested for advantages of sex and of increased mutation rates in yeast strains in two contrasting environments: a standard and relatively homogeneous laboratory environment of minimal medium in test tubes, and the variable environment of a mouse brain experienced by pathogenic strains. Evolving populations were founded as equal mixtures of sexual and obligately asexual genotypes. In the sexuals, cycles of sporulation, meiosis, and mating were induced approximately every 50 mitotic generations, with the asexuals undergoing sporulation but not ploidy cycles or recombination. In both environments, replicate negative control populations established with the same pair of strains were propagated with neither mating nor meiosis. In test tubes with no sex induced, sexuals were fixed in all five replicates within 250 mitotic generations, whereas in mice with no sex induced, asexuals were fixed in all four replicates by 170 generations. Inducing sex altered these outcomes in opposite directions in test tubes and mice, decreasing the fixation frequencies of sexuals in test tubes but increasing them in mice. These contrasts with asexual controls suggest an advantage for sex in mice but not in test tubes, although there was no difference between test tubes and mice in the numbers of populations fixed-for sexuals. In analogous experiments testing for an advantage of increased mutation rates, wild-type genotypes became fixed at the expense of mutators in every replicate of both test tube and mouse populations, indicating a disadvantage for mutators in both environments. Increased rates of point mutation do not appear to accelerate adaptation.     

Equal fecundity in asexual and sexual mollies (<Emphasis Type="Italic">Poecilia</Emphasis>)

The evolution and maintenance of sexual reproduction is still one of the major unresolved problems in evolutionary biology. Sexual reproduction is fraught with a number of costs as compared to asexual reproduction. For example, sexuals have to produce males, which–given a 1:1 sex ratio—results in a two-fold advantage for asexuals that do not produce males. Consequently, asexuals will outperform and replace sexuals over time assuming everything else is equal. Nonetheless, a few cases of closely related asexuals and sexuals have been documented to coexist stably in natural systems. We investigated the presence of a two-fold cost in a unique system of three closely related fish species: the asexual Amazon Molly (Poecilia formosa), and two sexual species, Sailfin Molly (P. latipinna) and Atlantic Molly (P. mexicana). Amazon Molly reproduce gynogenetically (by sperm dependent parthenogenesis) and always coexist with one of the sexual species, which serves as sperm donor. In the laboratory, we compared reproductive output between P. formosa and P. mexicana as well as P. formosa and P. latipinna. We found no differences in the fecundity in either comparison of a sexual and the asexual species. Under the assumption of a 1:1 sex ratio, the asexual Amazon Molly should consequently have a full two-fold advantage and be able to outcompete sexuals over time. Hence, the coexistence of the species pairs in nature presents a paradox still to be solved.     

Aging asexual lineages and the evolutionary maintenance of sex

Finite populations of asexual and highly selfing species suffer from a reduced efficacy of selection. Such populations are thought to decline in fitness over time due to accumulating slightly deleterious mutations or failing to adapt to changing conditions. These within‐population processes that lead nonrecombining species to extinction may help maintain sex and outcrossing through species level selection. Although inefficient selection is proposed to elevate extinction rates over time, previous models of species selection for sex assumed constant diversification rates. For sex to persist, classic models require that asexual species diversify at rates lower than sexual species; the validity of this requirement is questionable, both conceptually and empirically. We extend past models by allowing asexual lineages to decline in diversification rates as they age, that is nonrecombining lineages “senesce” in diversification rates. At equilibrium, senescing diversification rates maintain sex even when asexual lineages, at young ages, diversify faster than their sexual progenitors. In such cases, the age distribution of asexual lineages contains a peak at intermediate values rather than showing the exponential decline predicted by the classic model. Coexistence requires only that the average rate of diversification in asexuals be lower than that of sexuals.     

Switch from Asexual to Sexual Reproduction in the Planarian Dugesia ryukyuensis

Many metazoans convert the reproductive modes presumably depending upon the environmental conditions and/or the phase of life cycle, but the mechanisms underlying the switching from asexual to sexual reproduction, and vice versa, remain unknown. We established an experimental system, using an integrative biology approach, to analyze the mechanism in the planarian, Dugesia ryukyuensis (Kobayashi et al., 1999). Worms of exclusively asexual clone (OH strain) of the species gradually develop ovaries, testes and other sexual organs, then copulate and eventually lay cocoons filled with fertilized eggs, if they are fed with sexually mature worms of Bdellocephala brunnea (an exclusively oviparous species). This suggests the existence of a sexualizing substance(s) in sexually mature worms. Random inbreeding of experimentally sexualized worms (acquired sexuals) produces an F1 population of spontaneous sexuals (innate sexuals) and asexuals in a ratio of approximately 2:1. All regenerants from various portions of innate sexuals become sexuals. In the case of acquired sexuals, head fragments without sexual organs regenerated into asexuals though regenerants from other portions became sexuals. Thus, we conclude that neoblasts, the totipotent stem cells in the planarians, of acquired sexuals remain "asexual" and the worms require external supply of a sexualizing substance for the differentiation of sexual organs and gametes. On the other hand, some, if not all, neoblasts in innate sexuals are somehow "sexual" and do not require external supply of a sexualizing substance for the eventual differentiation of themselves and/or other neoblasts into sexual organs and gametes. It is also shown that sexuality in acquired sexuals is maintained by the putative sexualizing substance(s) of their own. The sexualization is closely coupled with cessation of fission, and the worms seem to have an unknown way of controlling the karyotype. Our integrative approach integrates multiple fields of study, including classic breeding, regeneration, and genetics experiments, as well as karyotyping, and biochemical and molecular biological analyses; none of which would have revealed much about the intricate mechanisms that regulate sex and fission in these animals.     

Can resource costs of polyploidy provide an advantage to sex?

The predominance of sexual reproduction despite its costs indicates that sex provides substantial benefits, which are usually thought to derive from the direct genetic consequences of recombination and syngamy. While genetic benefits of sex are certainly important, sexual and asexual individuals, lineages, or populations may also differ in physiological and life history traits that could influence outcomes of competition between sexuals and asexuals across environmental gradients. Here, we address possible phenotypic costs of a very common correlate of asexuality, polyploidy. We suggest that polyploidy could confer resource costs related to the dietary phosphorus demands of nucleic acid production; such costs could facilitate the persistence of sex in situations where asexual taxa are of higher ploidy level and phosphorus availability limits important traits like growth and reproduction. We outline predictions regarding the distribution of diploid sexual and polyploid asexual taxa across biogeochemical gradients and provide suggestions for study systems and empirical approaches for testing elements of our hypothesis.     

Comparing fecundity in parthenogenetic versus sexual populations of the freshwater snail Campeloma limum: is there a two‐fold cost of sex?

Abstract. The predominance of sexuality in eukaryotes remains an evolutionary paradox, given the "two-fold cost of sex" also known as the "cost of males." [Correction added after online publication 29 January 2009: in the preceding sentence, extraneous words were deleted.] As it requires two sexual parents to reproduce and only one parthenogenetic parent, parthenogens should have twice the reproductive rate compared with their sexual counterparts and their genes should spread twice as fast, if all else is equal. Yet, parthenogenesis is relatively rare and considered an evolutionary dead-end, while sexuality is the dominant form of reproduction in multicellular eukaryotes. Many studies have explored short-term benefits of sex that could outweigh its two-fold cost, but few have compared fecundity between closely related sexuals and parthenogens to first verify that "all else is equal" reproductively. We compared six fecundity measures between sexual and parthenogenetic populations of the freshwater snail, Campeloma limum , during a brooding cycle (1 year) across two drainages. Drainages were analyzed separately because of a significant drainage effect. In the Savannah drainage, fecundity was not significantly different between sexuals and parthenogens, even though parthenogens had significantly more empty egg capsules per brood. In the Ogeechee drainage, parthenogens had significantly more egg capsules with multiple embryos and more hatched embryos than sexuals. Taken over 1 year, embryo size was not significantly different between parthenogens and sexuals in either drainage. Given these results and the close proximity of sexual and parthenogenetic populations, it is perplexing why parthenogenetic populations have not completely replaced sexual populations in C. limum.     

EVOLUTIONARY FEEDBACKS BETWEEN REPRODUCTIVE MODE AND MUTATION RATE EXACERBATE THE PARADOX OF SEX

Evolutionary theory suggests that low mutation rates should favor the persistence of asexuals. Additionally, given the observation that most nonneutral mutations are deleterious, asexuality may strengthen selection for reduced mutation rates. This reciprocal relationship raises the possibility of a positive feedback loop between sex and mutation rate. We explored the consequences of this evolutionary feedback with an individual‐based model in which a sexual population is continually challenged by the introduction of asexual clones. We found that asexuals were more likely to spread in a population when mutation rates were able to evolve relative to a model in which mutation rates were held constant. In fact, under evolving mutation rates, asexuals were able to spread to fixation even when sexuals faced no cost of sex whatsoever. The added success of asexuals was the result of their ability to evolve lower mutation rates and thereby slow the process of mutation accumulation that otherwise limited their spread. Given the existence of ample mutation rate variation in natural populations, our findings show that the evolutionary feedback between sex and mutation rate may intensify the “paradox of sex,” supporting the argument that deleterious mutation accumulation alone is likely insufficient to overcome the reproductive advantage of asexual competitors in the short term.     

The cost of males in Daphnia pulex

Sex is paradoxical, because asexuals should replace their sexual ancestors by avoiding the demographic cost of producing males (hereafter referred to as the cost‐of‐males). Despite the large body of theoretical and empirical work dealing with the paradox of sex, the cost‐of‐males assumption has been rarely tested. In the present study, we tested the cost‐of‐males assumption in the cladoceran Daphnia pulex. Populations of this species consist of both cyclically parthenogenetic (i.e. sexuals) and obligately parthenogenetic (i.e. asexuals) lineages. In addition, some of the asexual lineages produce only female offspring, whereas others produce functional males, which can mate with sexual females. We compared the reproductive investment of sexuals, male‐producing asexuals, and non‐male‐producing asexuals when raised separately under various environmental conditions. We also determined the outcome of competition between pair‐wise combinations of these reproductive modes. The cost of males was evident when sexual and asexual females were raised separately: sexuals produced fewer female offspring. However, there was no cost of males when reproductive modes were raised in pairs, as sexuals won the competition with asexuals. Our results directly relate to the field conditions experienced by D. pulex. Sexuals might suffer the cost of males at the beginning of the season, when resource competition is low; but when conditions deteriorate as the population approaches carrying capacity, sexuals seem to be better competitors in spite of male production.     

Can phosphorus limitation contribute to the maintenance of sex? A test of a key assumption

Why sex is so common remains unclear; what is certain is that the predominance of sex despite its profound costs means that it must confer major advantages. Here, we use elemental and nucleic acid assays to evaluate a key element of a novel, integrative hypothesis considering whether sex might be favoured because of differences in body composition between sexuals and asexuals. We found that asexual Potamopyrgus antipodarum, a New Zealand snail, have markedly higher bodily phosphorus and nucleic acid content per unit mass than sexual counterparts. These differences coincide with and are almost certainly linked to the higher ploidy of the asexuals. Our results are the first documented body composition differences between sexual and asexual organisms, and the first detected phenotypic difference between sexual and asexual P. antipodarum, an important natural model system for the study of the maintenance of sex. These findings also verify a central component of our hypothesis that competition between diploid sexuals and polyploid asexuals could be influenced by phosphorus availability.     

Pollen profile,spatial structure,and access to sex in asexual hermaphrodites

Classical cost‐of‐sex models predict the rapid fixation of asexual reproduction. Coexistence of sexuals and asexuals is common among hermaphrodite plants, however, providing asexuals with access to sex via their male function; some of the sexually reproduced progeny they sire will be asexual. The ability of asexuals to sire progeny is often hindered by the production of poor quality pollen. Using cellular automata, it is shown that decreases in pollen quality in asexuals can greatly increase the period of coexistence of sexuals and asexuals and, consequently, the cumulative contribution of sex to asex. Extensive periods of coexistence are only likely, however, if pollen and seed are dispersed locally, in which case coexistence over thousands of generations can be achieved. It is argued that, with local dispersal, the negative relationship between pollen quality and the period of coexistence of sex and asex will result in patterns of geographic parthenogenesis in which asexuals that coexist with sexuals will exhibit a poor male function, whereas asexuals with a very efficient male function will occur in exclusively asexual populations. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 103 , 954–966.     

How populations persist when asexuality requires sex: the spatial dynamics of coping with sperm parasites

The twofold cost of sex implies that sexual and asexual reproduction do not coexist easily. Asexual forms tend to outcompete sexuals but may eventually suffer higher extinction rates, creating tension between short- and long-term advantages of different reproductive modes. The 'short-sightedness' of asexual reproduction takes a particularly intriguing form in gynogenetic species complexes, in which an asexual species requires sperm from a related sexual host species to trigger embryogenesis. Asexuals are then predicted to outcompete their host, after which neither species can persist. We examine whether spatial structure can explain continued coexistence of the species complex, and assess the evidence based on data on the Amazon molly (Poecilia formosa). A modification of the Levins metapopulation model creates two regions of good prospects for coexistence, connected by a region of poorer patch occupancy levels. In the first case, mate discrimination and/or niche differentiation keep local extinction rates low, and most patches contain both species; the other possibility resembles host-parasite dynamics where parasites frequently drive the host locally extinct. Several dynamical features are counterintuitive and relate to the parasitic nature of interactions in the species complex: for example, high local extinction rates of the asexual species can be beneficial for its own persistence. This creates a link from the evolution of sexual reproduction to that of prudent predation.     

THE MAINTENANCE OF OBLIGATE SEX IN FINITE,STRUCTURED POPULATIONS SUBJECT TO RECURRENT BENEFICIAL AND DELETERIOUS MUTATION

Although there is no known general explanation as to why sexual populations resist asexual invasion, previous work has shown that sexuals can outcompete asexuals in structured populations. However, it is currently unknown whether costly sex can be maintained with the weak structure that is commonly observed in nature. We investigate the conditions under which obligate sexuals resist asexual invasion in structured populations subject to recurrent mutation. We determine the level of population structure needed to disfavor asexuals, as calculated using the average F_st between all pairs of demes. We show that the critical F_st needed to maintain sex decreases as the population size increases, and approaches modest levels as observed in many natural populations. Sex is maintained with lower F_st if there are both advantageous and deleterious mutation, if mutation rates are sufficiently high, and if deleterious mutants have intermediate selective strengths, which maximizes the effect of Muller’s ratchet. Additionally, the critical F_st needed to maintain sex is lower when there are a large number of subpopulations. Lower F_st values are needed to maintain sex when demes vary substantially in their pairwise distances (e.g., when arrayed along one dimension), although this effect is often modest, especially if some long‐distance dispersal is present.     

THE DISTRIBUTION OF LIFE-HISTORY VARIATION IN THE DAPHNIA PULEX COMPLEX

In the midwestern United States the Daphnia pulex complex consists of a mosaic of sexual and asexual populations, providing a useful model system for studying the evolutionary forces underlying the maintenance of sex. One asexual and two sexual populations were surveyed for genetic variation for isozymes, mitochondrial DNA, and life-history characters. While the sexual populations exhibited substantial levels of genetic variance for fitness characters, no variation was detected in the asexual population at any level. However, a parallel survey among asexual clones derived from other ponds revealed large amounts of quantitative variation among clones, even among those with the same molecular profile. As a group, the asexuals are more variable for life histories than are the sexual populations. The molecular data indicate a relatively recent origin for the extant asexual D. pulex. The polyphyletic origin of these clones, combined with their microevolutionary potential, provides an explanation for their broad geographic distribution. The distribution of sex in the complex cannot be explained with the standard models that assume an invariant asexual population in reproductive isolation from the parental species. Although the frequency of asexuality may be driven by the spread of a sex-limited meiosis suppressor through sexual populations, the complete displacement of sexuality may be prevented by ecological distinctions between the two classes of individuals. On average, the asexuals are larger but produce smaller clutches than the sexuals.