Mutation accumulation in space and the maintenance of sexual reproduction

The maintenance of sexual reproduction remains one of the major puzzles of evolutionary biology, since, all else being equal, an asexual mutant should have a twofold fitness advantage over the sexual wildtype. Most theories suggest that sex helps either to purge deleterious mutations, or to adapt to changing environments. Both mechanisms have their limitations if they act in isolation because they require either high genomic mutation rates or very virulent pathogens, and it is therefore often thought that they must act together to maintain sex. Typically, however, these theories have in common that they are not based on spatial processes. Here, we show that local dispersal and local competition can explain the maintenance of sexual reproduction as a means of purging deleterious mutations. Using a spatially explicit individual-based model, we find that even with reasonably low genomic mutation rates and large total population sizes, asexual clones cannot invade a sexual population. Our results demonstrate how spatial processes affect mutation accumulation such that it can fully erode the twofold benefit of asexuality faster than an asexual clone can take over a sexual population. Thus, the cost of sex is generally overestimated in models that ignore the effects of space on mutation accumulation.     

Mutation Load under Vegetative Reproduction and Cytoplasmic Inheritance

For reasons that remain unclear, even multicellular organisms usually originate from a single cell. Here I consider the balance between deleterious mutations and selection against them in a population with obligate vegetative reproduction, when every offspring is initiated by more than one cell of a parent. The mutation load depends on the genomic deleterious mutation rate U, strictness of selection, number of cells which initiate an offspring n, and the relatedness among the initial cells. The load grows with increasing U, n and strictness of selection, and declines when an offspring is initiated by more closely related cells. If Un >> 1, the load under obligate vegetative reproduction may be substantially higher than under sexual or asexual reproduction, which may account for its rarity. In nature obligate vegetative reproduction seems to be more common and long term in taxa whose cytological features ensure a relatively low load under it. The same model also describes the mutation load under two other modes of inheritance: (1) uniparental transmission of organelles and (2) reproduction by division of multinuclear cells, where each daughter cell receives many nuclei. The load declines substantially when the deleterious mutation rate per organelle genome gets lower or when the number of nuclei in a cell sometimes drops. This may explain the small sizes of organelle genomes in sexual lineages and the presence of karyonic cycles in asexual unicellular multinuclear eukaryotes.     

Sexual reproduction and diversity: Connection between sexual selection and biological communities via population dynamics

Sexual reproduction is a mysterious phenomenon. Most animals and plants invest in sexual reproduction, even though it is more costly than asexual reproduction. Theoretical studies suggest that occasional or conditional use of sexual reproduction, involving facultative switching between sexual and asexual reproduction, is the optimal reproductive strategy. However, obligate sexual reproduction is common in nature. Recent studies suggest that the evolution of facultative sexual reproduction is prevented by males that coerce females into sexual fertilization; thus, sexual reproduction has the potential to enforce costs on a given species. Here, the effect of sex on biodiversity is explored by evaluating the reproductive costs arising from sex. Sex provides atypical selection pressure that favors traits that increase fertilization success, even at the expense of population growth rates, that is, sexual selection. The strength of sexual selection depends on the density of a given species. Sexual selection often causes strong negative effects on the population growth rates of species that occur at high density. Conversely, a species that reduces its density is released from this negative effect, and so increases its growth rate. Thus, this negative density-dependent effect on population growth that arises from sexual selection could be used to rescue endangered species from extinction, prevent the overgrowth of common species and promote the coexistence of competitive species. Recent publications on sexual reproduction provide several predictions related to the evolution of reproductive strategies, which is an important step toward integrating evolutionary dynamics, demographic dynamics and community dynamics.     

Strong sexual selection in males against a mutation load that reduces offspring production in seed beetles

Theory predicts that sexual reproduction can increase population viability relative to asexual reproduction by allowing sexual selection in males to remove deleterious mutations from the population without large demographic costs. This requires that selection acts more strongly in males than females and that mutations affecting male reproductive success have pleiotropic effects on population productivity, but empirical support for these assumptions is mixed. We used the seed beetle Callosobruchus maculatus to implement a three‐generation breeding design where we induced mutations via ionizing radiation (IR) in the F₀ generation and measured mutational effects (relative to nonirradiated controls) on an estimate of population productivity in the F₁ and effects on sex‐specific competitive lifetime reproductive success (LRS) in the F₂. Regardless of whether mutations were induced via F₀ males or females, they had strong negative effects on male LRS, but a nonsignificant influence on female LRS, suggesting that selection is more efficient in removing deleterious alleles in males. Moreover, mutations had seemingly shared effects on population productivity and competitive LRS in both sexes. Thus, our results lend support to the hypothesis that strong sexual selection on males can act to remove the mutation load on population viability, thereby offering a benefit to sexual reproduction.     

Radical amino acid mutations persist longer in the absence of sex

Harmful mutations are ubiquitous and inevitable, and the rate at which these mutations are removed from populations is a critical determinant of evolutionary fate. Closely related sexual and asexual taxa provide a particularly powerful setting to study deleterious mutation elimination because sexual reproduction should facilitate mutational clearance by reducing selective interference between sites and by allowing the production of offspring with different mutational complements than their parents. Here, we compared the rate of removal of conservative (i.e., similar biochemical properties) and radical (i.e., distinct biochemical properties) nonsynonymous mutations from mitochondrial genomes of sexual versus asexual Potamopyrgus antipodarum, a New Zealand freshwater snail characterized by coexisting and ecologically similar sexual and asexual lineages. Our analyses revealed that radical nonsynonymous mutations are cleared at higher rates than conservative changes and that sexual lineages eliminate radical changes more rapidly than asexual counterparts. These results are consistent with reduced efficacy of purifying selection in asexual lineages allowing harmful mutations to remain polymorphic longer than in sexual lineages. Together, these data illuminate some of the population‐level processes contributing to mitochondrial mutation accumulation and suggest that mutation accumulation could influence the outcome of competition between sexual and asexual lineages.     

The effects of deleterious mutations in cyclically parthenogenetic organisms

Cyclically parthenogenetic organisms experience benefits of both sexual and asexual reproductive modes in a constant environment. Sexual reproduction generates new genotypes and may facilitate the purging of deleterious mutations whereas asexuality has a two-fold advantage and enables maintenance of well-fitted genotypes. Asexual reproduction can have a drawback as increased linkage may lead to the accumulation of deleterious mutations. This study presents the results of Monte Carlo simulations of small and infinite diploid populations, with deleterious mutations occurring at multiple loci. The recombination rate and the length of the asexual period, interrupted by sexual reproduction, are allowed to vary. Here I show that the fitness of cyclical parthenogenetic population is dependent on the length of the asexual period. Increased length of the asexual period can lead both to increased segregational load following sexual reproduction and to a stronger effect of deleterious mutations on variation at a linked neutral marker, either by reducing or increasing the variation.     

Muller's ratchet and the accumulation of favourable mutations

Under the influence of recurrent deleterious mutation and selection, asexual and sexual populations reach a deterministic equilibrium with individuals carrying 0,1,2,. . . harmful mutations. When a favourable mutation (aA) occurs in an asexual population it will usually occur in an individual who has one or more (k) deleterious mutations. Muller's ratchet then applies as A will thereafter never occur in an individual with less than k mutations. If the selective advantage of A is less than the selective disadvantage of k harmful mutations then A will not spread. If it is greater it may spread carrying k deleterious mutations to fixation. Sexual populations are not affected in this way. A will spread through the population experiencing genomes with 0,1,2,. . . deleterious mutations in accordance with the deterministic equilibrium.     

An advantage of sexual reproduction in a rapidly changing environment.

When an environmental change imposes strong directional selection, there are two advantages of sexual reproduction. First, an asexual population is limited to the most extreme individual in the population, and progress under directional selection can go no farther without mutation; no such limitation applies to a sexual population. Second, more quantitatively, directional selection in an asexual population monotonically decreases the variance, whereas the variance of a sexual population quickly reaches a steady value; this difference remains even if the direction of selection occasionally changes. With realistic environmental changes small alterations in any particular measurement or trait are usually sufficient to keep up with the changes, but fitness, since it depends on a large number of traits, will be selected with greater intensity, which may be enough to confer a distinct advantage on sexual reproduction. This applies particularly to a large or rapid environmental change. Eventually mutation will enhance the variance, but by then it may be too late to prevent extinction of asexual strains.     

Deleterious mutation accumulation in asexual Timema stick insects

Sexual reproduction is extremely widespread in spite of its presumed costs relative to asexual reproduction, indicating that it must provide significant advantages. One postulated benefit of sex and recombination is that they facilitate the purging of mildly deleterious mutations, which would accumulate in asexual lineages and contribute to their short evolutionary life span. To test this prediction, we estimated the accumulation rate of coding (nonsynonymous) mutations, which are expected to be deleterious, in parts of one mitochondrial (COI) and two nuclear (Actin and Hsp70) genes in six independently derived asexual lineages and related sexual species of Timema stick insects. We found signatures of increased coding mutation accumulation in all six asexual Timema and for each of the three analyzed genes, with 3.6- to 13.4-fold higher rates in the asexuals as compared with the sexuals. In addition, because coding mutations in the asexuals often resulted in considerable hydrophobicity changes at the concerned amino acid positions, coding mutations in the asexuals are likely associated with more strongly deleterious effects than in the sexuals. Our results demonstrate that deleterious mutation accumulation can differentially affect sexual and asexual lineages and support the idea that deleterious mutation accumulation plays an important role in limiting the long-term persistence of all-female lineages.     

Asexual Experimental Evolution of Yeast Does Not Curtail Transposable Elements

Compared with asexual reproduction, sex facilitates the transmission of transposable elements (TEs) from one genome to another, but boosts the efficacy of selection against deleterious TEs. Thus, theoretically, it is unclear whether sex has a positive net effect on TE’s proliferation. An empirical study concluded that sex is at the root of TE’s evolutionary success because the yeast TE load was found to decrease rapidly in approximately 1,000 generations of asexual but not sexual experimental evolution. However, this finding contradicts the maintenance of TEs in natural yeast populations where sexual reproduction occurs extremely infrequently. Here, we show that the purported TE load reduction during asexual experimental evolution is likely an artifact of low genomic sequencing coverages. We observe stable TE loads in both sexual and asexual experimental evolution from multiple yeast data sets with sufficient coverages. To understand the evolutionary dynamics of yeast TEs, we turn to asexual mutation accumulation lines that have been under virtually no selection. We find that both TE transposition and excision rates per generation, but not their difference, tend to be higher in environments where yeast grows more slowly. However, the transposition rate is not significantly higher than the excision rate and the variance of the TE number among natural strains is close to its neutral expectation, suggesting that selection against TEs is at best weak in yeast. We conclude that the yeast TE load is maintained largely by a transposition–excision balance and that the influence of sex remains unclear.     

Do males pay for sex? Sex‐specific selection coefficients suggest not

Selection acting on males can reduce mutation load of sexual relative to asexual populations, thus mitigating the twofold cost of sex, provided that it seeks and destroys the same mutations as selection acting on females, but with higher efficiency. This could happen due to sexual selection—a potent evolutionary force that in most systems predominantly affects males. We used replicate populations of red flour beetles (Tribolium castaneum) to study sex‐specific selection against deleterious mutations introduced with ionizing radiation. We found no evidence for selection being stronger in males than in females; in fact, we observed a nonsignificant trend in the opposite direction. This suggests that selection on males does not reduce mutation load below the level expected under the (hypothetical) scenario of asexual reproduction. Additionally, we employed a novel approach, based on a simple model, to quantify the relative contributions of sexual and offspring viability selection to the overall selection observed in males. We found them to be similar in magnitude; however, only the offspring viability component was statistically significant. In summary, we found no support for the hypothesis that selection on males in general, and sexual selection in particular, contributes to the evolutionary maintenance of sex.     

Recessive mutations and the maintenance of sex in structured populations

The evolutionary maintenance of sexual reproduction remains a controversial problem. It was recently shown that recessive deleterious mutations create differences in the mutation load of sexual vs. asexual populations. Here we show that low levels of population structure or inbreeding can greatly enhance the importance of recessive deleterious mutations in the context of sexual vs. asexual populations. With population structure, the cost of sex can be substantially reduced or even eliminated for realistic levels of dominance.     

Environmental variance in male mating success modulates the positive versus negative impacts of sexual selection on genetic load

Sexual selection on males is predicted to increase population fitness, and delay population extinction, when mating success negatively covaries with genetic load across individuals. However, such benefits of sexual selection could be counteracted by simultaneous increases in genome-wide drift resulting from reduced effective population size caused by increased variance in fitness. Resulting fixation of deleterious mutations could be greatest in small populations, and when environmental variation in mating traits partially decouples sexual selection from underlying genetic variation. The net consequences of sexual selection for genetic load and population persistence are therefore likely to be context dependent, but such variation has not been examined. We use a genetically explicit individual-based model to show that weak sexual selection can increase population persistence time compared to random mating. However, for stronger sexual selection such positive effects can be overturned by the detrimental effects of increased genome-wide drift. Furthermore, the relative strengths of mutation-purging and drift critically depend on the environmental variance in the male mating trait. Specifically, increasing environmental variance caused stronger sexual selection to elevate deleterious mutation fixation rate and mean selection coefficient, driving rapid accumulation of drift load and decreasing population persistence times. These results highlight an intricate balance between conflicting positive and negative consequences of sexual selection on genetic load, even in the absence of sexually antagonistic selection. They imply that environmental variances in key mating traits, and intrinsic genetic drift, should be properly factored into future theoretical and empirical studies of the evolution of population fitness under sexual selection.     

Genetic loads under fitness‐dependent mutation rates

Abstract Although much theory depends on the genome‐wide rate of deleterious mutations, good estimates of the mutation rate are scarce and remain controversial. Furthermore, mutation rate may not be constant, and a recent study suggests that mutation rates are higher in mildly stressful environments. If mutation rate is a function of condition, then individuals carrying more mutations will tend to be in worse condition and therefore produce more mutations. Here I examine the mean fitnesses of sexual and asexual populations evolving under such condition‐dependent mutation rates. The equilibrium mean fitness of a sexual population depends on the shape of the curve relating fitness to mutation rate. If mutation rate declines synergistically with increasing condition the mean fitness will be much lower than if mutation rate declines at a diminishing rate. In contrast, asexual populations are less affected by condition‐dependent mutation rates. The equilibrium mean fitness of an asexual population only depends on the mutation rate of the individuals in the least loaded class. Because such individuals have high fitness and therefore a low mutation rate, asexual populations experience less genetic load than sexual populations, thus increasing the twofold cost of sex.     

Evolutionary Consequences of Mutation and Selection within an Individual

Whether in sexual or asexual organisms, selection among cell lineages during development is an effective way of eliminating deleterious mutations. Using a mathematical analysis, we find that relatively small differences in cell replication rates during development can translate into large differences in the proportion of mutant cells within the adult, especially when development involves a large number of cell divisions. Consequently, intraorganismal selection can substantially reduce the deleterious mutation rate observed among offspring as well as the mutation load within a population, because cells rather than individuals provide the selective ``deaths' necessary to stem the tide of deleterious mutations. The reduction in mutation rate among offspring is more pronounced in organisms with plastic development than in those with structured development. It is also more pronounced in asexual organisms that produce multicellular rather than unicellular offspring. By effecting the mutation rate, intraorganismal selection may have broad evolutionary implications; as an example, we consider its influence on the evolution of ploidy levels, finding that cell-lineage selection is more effective in haploids and tends to favor their evolution.     

Reducing mutation load through sexual selection on males

Mutation load is a key parameter in evolutionary theories, but relatively little empirical information exists on the mutation load of populations, or the elimination of this load through selection. We manipulated the opportunity for sexual selection within a mutation accumulation divergence experiment to determine how sexual selection on males affected the accumulation of mutations contributing to sexual and nonsexual fitness. Sexual selection prevented the accumulation of mutations affecting male mating success, the target trait, as well as reducing mutation load on productivity, a nonsexual fitness component. Mutational correlations between mating success and productivity (estimated in the absence of sexual selection) were positive. Sexual selection significantly reduced these fitness component correlations. Male mating success significantly diverged between sexual selection treatments, consistent with the fixation of genetic differences. However, the rank of the treatments was not consistent across assays, indicating that the mutational effects on mating success were conditional on biotic and abiotic context. Our experiment suggests that greater insight into the genetic targets of natural and sexual selection can be gained by focusing on mutational rather than standing genetic variation, and on the behavior of trait variances rather than means.     

Rates of deleterious mutation and the evolution of sex in Caenorhabditis

A variety of models propose that the accumulation of deleterious mutations plays an important role in the evolution of breeding systems. These models make predictions regarding the relative rates of protein evolution and deleterious mutation in taxa with contrasting modes of reproduction. Here we compare available coding sequences from one obligately outcrossing and two primarily selfing species of Caenorhabditis to explore the potential for mutational models to explain the evolution of breeding system in this clade. If deleterious mutations interact synergistically, the mutational deterministic hypothesis predicts that a high genomic deleterious mutation rate (U) will offset the reproductive disadvantage of outcrossing relative to asexual or selfing reproduction. Therefore, C. elegans and C. briggsae (both largely selfing) should both exhibit lower rates of deleterious mutation than the obligately outcrossing relative C. remanei. Using a comparative approach, we estimate U to be equivalent (and < 1) among all three related species. Stochastic mutational models, Muller's ratchet and Hill-Robertson interference, are expected to cause reductions in the effective population size in species that rarely outcross, thereby allowing deleterious mutations to accumulate at an elevated rate. We find only limited support for more rapid molecular evolution in selfing lineages. Overall, our analyses indicate that the evolution of breeding system in this group is unlikely to be explained solely by available mutational models.     

The fate of transposable elements in asexual populations

Sexual reproduction and recombination are important for maintaining a stable copy number of transposable elements (TEs). In sexual populations, elements can be contained by purifying selection against host carriers with higher element copy numbers; however, in the absence of sex and recombination, asexual populations could be driven to extinction by an unchecked proliferation of TEs. Here we provide a theoretical framework for analyzing TE dynamics under asexual reproduction. Analytic results show that, in an infinite asexual population, an equilibrium in copy number is achieved if no element excision is possible, but that all TEs are eliminated if there is some excision. In a finite population, computer simulations demonstrate that small populations are driven to extinction by a Muller's ratchet-like process of element accumulation, but that large populations can be cured of vertically transmitted TEs, even with excision rates well below transposition rates. These results may have important consequences for newly arisen asexual lineages and may account for the lack of deleterious retrotransposons in the putatively ancient asexual bdelloid rotifers.     

Evolution of sex: role of deleterious mutation and mobile elements

Prevalence of sexual reproduction is still enigma. The main character of sex is alleles mixing that could be advantageous either in unstable environment (in this case sex provides high temp of evolution) or in unstable genotype (in this case sex provides purge of genome from deleterious mutations). As long as not all species inhabit highly changeable environments, variation of genotypes is more important factor. As the majority of new mutations is deleterious, effective mechanism of genome purging is needed. Maintenance of "purging mechanism" may be a single role of sex. Two promising mutational hypotheses--clade selection (Muller's ratchet and Nunney's hypothesis) and mutational deterministic hypothesis of Kondrashov claim that more effective elimination of slightly-deleterious mutations provides main advantage to sexual population in comparison with asexual. Despite prima facie similarity, these hypotheses differ in mechanisms, work at different temporal scales and have different consequences. Kondrashov's hypothesis reveals short-term advantage of sexual reproduction, and thus, based on the individual selection. Clade selection displays long-term advantage of sexual reproduction that could be realized only by group selection. The role of mobile elements in evolution of sexual reproduction is also discussed. Firstly, mobile elements ("sexual molecular parasites") can complicate the problem: having been domesticated in asexual genomes and remaining active in sexual genomes they lead to higher mutational rate in sexual organisms and so violate assumption critical for both mutational hypotheses of "other things being equal". Secondly, mobile elements could be leader factor of origin of sex (hypothesis proposed by Hickey). Because theory of group selection could explain maintenance of sex, but not its origin, mobile elements could induce the origin of sex but were not able to maintain it, so the next scenario of evolution of sex is proposed: mobile elements induced origin of sex, which was established later by group selection because provided long term benefit (Muller's ratchet and Nunney's hypothesis). So, on all stages of evolution, sex was not advantageous for the organism per se.     

Dynamic mutation-selection balance as an evolutionary attractor

The vast majority of mutations are deleterious and are eliminated by purifying selection. Yet in finite asexual populations, purifying selection cannot completely prevent the accumulation of deleterious mutations due to Muller's ratchet: once lost by stochastic drift, the most-fit class of genotypes is lost forever. If deleterious mutations are weakly selected, Muller's ratchet can lead to a rapid degradation of population fitness. Evidently, the long-term stability of an asexual population requires an influx of beneficial mutations that continuously compensate for the accumulation of the weakly deleterious ones. Hence any stable evolutionary state of a population in a static environment must involve a dynamic mutation-selection balance, where accumulation of deleterious mutations is on average offset by the influx of beneficial mutations. We argue that such a state can exist for any population size N and mutation rate U and calculate the fraction of beneficial mutations, ε, that maintains the balanced state. We find that a surprisingly low ε suffices to achieve stability, even in small populations in the face of high mutation rates and weak selection, maintaining a well-adapted population in spite of Muller's ratchet. This may explain the maintenance of mitochondria and other asexual genomes.