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.     

Do ecological niches differ between sexual and asexual lineages of an aphid species?

According to environmental-based theories on the maintenance of sexual reproduction, sexual and asexual populations may coexist if they occupy different ecological niches. The aphid Rhopalosiphum padi offers a good opportunity to test this hypothesis since sexual and asexual lineages show local coexistence during a large part of their respective life-cycles. Because these two reproductive variants are morphologically identical but genetically distinct, we first characterized them using genetic markers in populations of R. padi in areas where sexual and asexual lineages may occur in sympatry. We then inferred the natal host plant of sexual and asexual genotypes by analysing stable isotopic ratios and showed that sexual ones mostly originated from C₃ Poaceae while asexual ones originated from C₃ and C₄ plants, although the majority came from C₄ Poaceae. These findings indicate that ecological niches of sexual and asexual lineages of R. padi differ, offering a plausible explanation for the local coexistence of the two reproductive modes in this species through habitat specialisation.     

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.     

MUTATIONAL MELTDOWNS IN SEXUAL POPULATIONS

Although it is widely acknowledged that the gradual accumulation of mildly deleterious mutations is an important source of extinction for asexual populations, it is generally assumed that this process is of little relevance to sexual species. Here we present results, based on computer simulations and supported by analytical approximations, that indicate that mutation accumulation in small, random-mating monoecious populations can lead to mean extinction times less than a few hundred to a few thousand generations. Unlike the situation in obligate asexuals in which the mean time to extinction (t?_e) increases more slowly than linearly with the population carrying capacity (K), t?_e increases approximately exponentially with K in outcrossing sexual populations. The mean time to extinction for obligately selfing populations is shown to be equivalent to that for asexual populations of the same size, but with half the mutation rate and twice the mutational effect; this suggests that obligate selfing, like obligate asexuality, is inviable as a long-term reproductive strategy. Under all mating systems, the mean time to extinction increases relatively slowly with the logarithm of fecundity, and mutations with intermediate effects (similar to those observed empirically) cause the greatest risk of extinction. Because our analyses ignore sources of demographic and environmental stochasticity, which have synergistic effects that exacerbate the accumulation of deleterious mutations, our results should yield liberal upper bounds to the mean time to extinction caused by mutational degradation. Thus, deleterious mutation accumulation cannot be ruled out generally as a significant source of extinction vulnerability in small sexual populations or as a selective force influencing mating-system evolution.     

Evolution of longevity in primates

Evolution of maximum lifespan potential (MLP) and its possible relation to the evolution of extra-brain functions are investigated in the primates. MLP is related to a species' characteristic aging rate and is considered a basic biological property of an organism. MLP may be of more importance than realized in the past in determining the evolutionary success of a species. It is related to the postnatal development rate, the length of time general vigor is maintained, the length of reproductive period, generation time and the time available for learning and teaching behavior. Three other parameters are considered to be importantly related to MLP: MLP calorie consumption (MCC), encephalization quotient (EQ) and extra number of cortical neurons (N_c). MCC is calculated as the product of MLP and specific metabolic rate (SMR) and is considered to represent total “life-capacity” of an organism. It is of potential value in studying the biological mechanisms involved in the evolution of MLP. Brain function is estimated by the Jerison EQ and N_c parameters. These parameters estimate the “extra” brain capacity involved in functions beyond normal body requirements. The rate of change in MLP and N_c per unit time occurring during an ancestral-descendant sequence is used to estimate the biological complexity of the genetic processes which have evolved in governing the rate of expression of the general aging process and increasing brain function. The average rate of change of MLP during the emergence of the primates was analyzed by the difference between MLP in closely related living primate species and the evolutionary time of appearance of a common ancestor. MLP, SMR, MCC, EQ and N_c were estimated from fossil cranial capacity and body weight measurements. The rate of change in these values was calculated according to the time of appearance of the fossil species. MLP and N_c were found to increase together and reached their highest rate of increase approximately 200,000 years ago along the hominid ancestral-descendant sequence leading to modern man. The high rate of increase of these parameters suggests that few genetic changes were responsible. The general increase in MLP during the evolution of the primate species indicates that a corresponding general decrease in mutation rate may have occurred. The high levels of MLP, MCC, EQ and N_c represented in the living primates, as compared to other mammals, are considered to represent a major characteristic determining their evolutionary success.     

Assessment strategy and the evolution of fighting behaviour

The view is examined that the adaptive value of conventional aspects of fighting behaviour is for assessment of relative RHP (resource holding power) of the combatants. Outcomes of aggressive disputes should be decided by each individual's fitness budget available for expenditure during a fight (determined by the fitness difference between adoption of alternative strategies, escalation or withdrawal without escalation) and on the rate of expenditure of the fitness budget if escalation occurs (determined by the RHPs of the combatants). Thus response thresholds for alternative strategies (“assessments”) will be determined by natural selection on a basis of which opponent is likely to expend its fitness budget first, should escalation occur. This “loser” should retreat (before escalation) and the winner should stay in possession of the resource. Many aggressive decisions depend on whether one is a resource holder, or an attacker. Assuming the RHP of the combatants to be equal, there are many instances of fitness pay-off imbalances between holder and attacker which should weight the dispute outcome in favour of one or other opponent by allowing it a greater expendable fitness budget. Usually the weighting favours the holder; the attacker therefore needs a correspondingly higher RHP before it may be expected to win. This is not invariably the case, and much observed data fits the predictions of this sort of model. If assessments are perfect and budget expenditure rates exactly predictable, then there would never seem to be any case for escalation. Escalation can be explained in terms of injury inflictions (expenditures) occurring as discrete events; i.e. as “bouts” won or lost during fighting. Assessment can give only a probabilistic prediction of the outcome of a bout. A simple model is developed to investigate escalation situations. Each combatant assesses relative RHP; this correlates with an absolute probability of winning the next bout (c_abs). The stake played for is infliction of loss of RHP and is determined by the fitness budgets of the opponents. (Each individual plays for the withdrawal of its opponent.) This defines a critical probability of winning (c_crit) for each combatant, above which escalation is the favourable strategy (c_abs > c_crit) and below which withdrawal is favourable (c_abs < c_crit). Escalation should occur only where c_abs-c_crit is positive for both combatants. This model gives predictions compatible with the observations, indicating that RHP loss alone can be adequate to explain withdrawal: escalation behaviour. Withdrawal tendency will be increased by low searching costs. Escalations should be restricted to closely matched RHP opponents if RHP disparity is the major imbalance. Outside the “escalation range” of a given individual, the higher RHP individual wins and the lower one loses (i.e. it should withdraw after conventional display). RHP disparity and holder: attacker imbalance should both interact to shape the observed pattern, though their relative importances will depend on species and situation. In some instances selection may favour immediate withdrawal from an occupied territory even without assessment of RHP.     

A Ruby in the Rubbish: Beneficial Mutations, Deleterious Mutations and the Evolution of Sex

This study presents a mathematical model in which a single beneficial mutation arises in a very large population that is subject to frequent deleterious mutations. The results suggest that, if the population is sexual, then the deleterious mutations will have little effect on the ultimate fate of the beneficial mutation. However, if most offspring are produced asexually, then the probability that the beneficial mutation will be lost from the population may be greatly enhanced by the deleterious mutations. Thus, sexual populations may adapt much more quickly than populations where most reproduction is asexual. Some of the results were produced using computer simulation methods, and a technique was developed that allows treatment of arbitrarily large numbers of individuals in a reasonable amount of computer time. This technique may be of prove useful for the analysis of a wide variety of models, though there are some constraints on its applicability. For example, the technique requires that reproduction can be described by Poisson processes.     

Mutagenicity of nitrofuran derivatives, including furylfuramide, a food preservative.

The effects of sodium azide (NaN₃) in combination with diethyl sulfate (dES) or N-methyl-N′-nitrosourea (MNH) on mutation frequency in barley were studied. It was found that sodium azide produced high frequencies of chlorophyll mutations when used alone and has a synergistic effect on mutation yields following MNH treatments. However, the mutation frequency was decreased whe azide was applied following dES treatment of seeds. The mutagenic efficiency of azide was found to be high, possibly because of low “physiological” damage. The synergistic increase in mutation yields by MNH and azide treatment indicates that azide has unusual promise as a mutagen for both practical and research applications.     

Sexual recombination under the joint effects of mutation,selection, and random sampling drift

The advantage or disadvantage of sexual reproduction or recombination for the accumulation of mutant genes in a population is studied under the joint effects of recurrent mutations, selection, and random sampling drift. To obtain the rate at which mutant genes are incorporated three different methods are used; numerical integration of Kolmogorov backward equations, simulation of stochastic difference equations, and Monte Carlo experiments. The first two methods are used in a two-locus system to obtain the fixation probability of double mutants and other related quantities under five different selection models. The third one is conducted for a multiple-locus system and the rate of accumulation of mutant genes per locus is studied. Comparison of the results between sexual and asexual populations shows that the effect of recombination depends on initial linkage disequilibrium, mutation rate v, selection intensity s, and population size N_e. The mode of selection is also an important factor and the large effect of recombination is observed when mutant genes are individually deleterious but collectively favorable. Under a given model of selection, the great advantage or disadvantage of recombination is achieved when a large extent of genetic polymorphism is produced not by mutation but by recombination. Extreme values of N_es and N_ev make the effect insignificant. The results of Monte Carlo experiments also reveal the presence of interaction between selection and sampling drift even when the loci segregate independently and selection is multiplicative. Although this interaction is usually small, there are cases in which one locus theory cannot be used freely. In those cases, the effect of recombination is prominent and one locus theory gives an overestimate of the rate.     

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.     

ENVIRONMENTAL STRESS AND THE MAINTENANCE OF SEX IN A FRESHWATER SNAIL

Synergism among mutations can lead to an advantage to sexual reproduction, provided mutation rates are high enough (the mutational deterministic hypothesis). Here we tested the idea that competition for food can increase the advantage to sexual reproduction, perhaps by increasing the synergism among mutations in asexual individuals. We compared the survivorship of sexual and asexual snails (Potamopyrgus antipodarum) under two treatments: starved and fed. We predicted higher mortality for asexual snails when starved, but found that sexual and asexual individuals survived at the same rate, independent of treatment. These results suggest that the distribution of sex in this snail may not be explained by variation in competition among populations.     

Sex or Sanctuary: How do Asexual Worms Survive the Winter?

The common and geographically widespread freshwater worm Stylaria lacustris (Linnaeus, 1767) (Oligochaeta: Naididae) typically reproduces asexually through transverse paratomic fission during the spring, summer, and autumn. With the onset of shorter days and colder conditions, S. lacustris becomes a sexually mature simultaneous hermaphrodite and produces resting eggs that are capable of overwintering. However, like many naidid species, S. lacustris shows widespread variation in reproductive mode with some populations never attaining sexual maturity and others apparently exhibiting both sexual and obligately asexual genotypes. How then do obligately asexual genotypes and populations survive the harsh winter conditions? Extensive winter sampling of two, largely obligately, asexual populations of S. lacustris in Oxfordshire, UK, demonstrate that adult individuals can survive over the winter, but at densities way below that normally detected by standard sampling procedures. Laboratory experiments confirm that asexual individuals can survive cold water conditions but not freezing (unlike sexually produced cocoons). The proposed advantage of this seemingly risky reproductive strategy is that naidids like Stylaria, with their remarkably fast asexual reproductive rate, can respond instantly to favourable change in conditions.     

Exceptional cryptic diversity and multiple origins of parthenogenesis in a freshwater ostracod

The persistence of asexual reproduction in many taxa depends on a balance between the origin of new asexual lineages and the extinction of old ones. This turnover determines the diversity of extant asexual populations and so influences the interaction between sexual and asexual modes of reproduction. Species with mixed reproduction, like the freshwater ostracod (Crustacea) morphospecies Eucypris virens, are a good model to examine these dynamics. This species is also a geographic parthenogen, in which sexual females and males co-exist with asexual females in the circum-Mediterranean area only, whereas asexual females occur all over Europe. A molecular phylogeny of E. virens based on the mitochondrial COI and 16S fragments is presented. It is characterised by many distinct clusters of haplotypes which are either exclusively sexual or asexual, with only one exception, and are often separated by deep branches. Analysis of the phylogeny reveals an astonishing cryptic diversity, which indicates the existence of a species complex with more than 40 cryptic taxa. We therefore suggest a revision of the single species status of E. virens. The phylogeny indicates multiple transitions from diverse sexual ancestor populations to asexuality. Although many transitions appear to be ancient, we argue that this may be an artefact of the existence of unsampled or extinct sexual lineages.     

Recent Taxonomic Developments with <Emphasis Type="Italic">Candida</Emphasis> and Other Opportunistic Yeasts

Increases in susceptible patient populations and advances in identification methods have resulted in the continued recognition of novel yeasts as agents of human infection. Most of these agents are members of the well-recognized genera Candida, Cryptococcus, Trichosporon, and Rhodotorula. Some of these agents are “cryptic species,” members of species complexes, and may not be detectable using classical carbohydrate assimilation-based methods of yeast identification. Such species require DNA- or MALDI-based methods for correct identification, although sporadic isolates may not routinely require delineation to the individual species level. The coming end of the fungal taxonomy rules requiring separate names for sexual and asexual forms of the same fungus will hopefully allow greater clarity, as names for medically important yeast can now be based on the needs of the medical mycology community and the common goal of better communication between laboratory and clinician.     

Density,parasitism, and sexual reproduction are strongly correlated in lake Daphnia populations

Many organisms can reproduce both asexually and sexually. For cyclical parthenogens, periods of asexual reproduction are punctuated by bouts of sexual reproduction, and the shift from asexual to sexual reproduction has large impacts on fitness and population dynamics. We studied populations of Daphnia dentifera to determine the amount of investment in sexual reproduction as well as the factors associated with variation in investment in sex. To do so, we tracked host density, infections by nine different parasites, and sexual reproduction in 15 lake populations of D. dentifera for 3 years. Sexual reproduction was seasonal, with male and ephippial female production beginning as early as late September and generally increasing through November. However, there was substantial variation in the prevalence of sexual individuals across populations, with some populations remaining entirely asexual throughout the study period and others shifting almost entirely to sexual females and males. We found strong relationships between density, prevalence of infection, parasite species richness, and sexual reproduction in these populations. However, strong collinearity between density, parasitism, and sexual reproduction means that further work will be required to disentangle the causal mechanisms underlying these relationships.     

Gene-flow between niches facilitates local adaptation in sexual populations

In sexual populations, gene-flow between niches is predicted to have differential consequences on local adaptation contingent upon the nature of trade-offs underlying local adaptation. Sex retards local adaptation if antagonistic pleiotropy underlies trade-offs, but facilitates adaptation if mutation accumulation underlies trade-offs. We evaluate the effect of sex in heterogeneous environments by manipulating gene-flow between two niches in sexual and asexual populations using steady-state microcosm experiments with yeast. We find that only sex in the presence of gene-flow promotes simultaneous local adaptation to different niches, presumably as this exposes mutations neutrally accrued in alternate niches to selection. This finding aligns with work showing mutation accumulation underlies trade-offs to local adaptation in asexual microbes, and with inferences of divergence in the presence of gene-flow in natural sexual populations. This experiment shows that sex may be of benefit in heterogeneous environments, and thus helps explain why sex has been maintained more generally.     

Genetic Variation in Fusarium Section Liseola from No-Till Maize in Argentina

Strains of Fusarium species belonging to section Liseola cause stalk and ear rot of maize and produce important mycotoxins, such as fumonisins. We isolated two species, Fusarium verticillioides (Gibberella fujikuroi mating population A) and Fusarium proliferatum (G. fujikuroi mating population D) from maize cultivated under no-till conditions at five locations in the Córdoba province of Argentina. We determined the effective population number for mating population A (N_e) and found that the N_e for mating type was 89% of the count (total population) and that the N_e for male or hermaphrodite status was 36%. Thus, the number of strains that can function as the female parent limits N_e, and sexual reproduction needs to occur only once every 54 to 220 asexual generations to maintain this level of sexual fertility. Our results indicate that the fungal populations isolated from no-till maize are similar to those recovered from maize managed with conventional tillage. We placed 36 strains from mating population A into 28 vegetative compatibility groups (VCGs). Of the 13 strains belonging to five multimember VCGs, only 2 isolates belonging to one VCG were clones based on amplified fragment length polymorphism (AFLP) fingerprints. Members of the other four multimember VCGs had an average similarity index of 0.89, and members of one VCG were no more closely related to other members of the same VCG than they were to other members of the population as a whole. This finding suggests that the common assumption that strains in the same VCG are either clonal or very closely related needs to be examined in more detail. The variability observed with AFLPs and VCGs suggests that sexual reproduction may occur more frequently than estimated by N_e.     

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 Exact Distributions of F IS under Partial Asexuality in Small Finite Populations with Mutation

Reproductive systems like partial asexuality participate to shape the evolution of genetic diversity within populations, which is often quantified by the inbreeding coefficient F _IS. Understanding how those mating systems impact the possible distributions of F _IS values in theoretical populations helps to unravel forces shaping the evolution of real populations. We proposed a population genetics model based on genotypic states in a finite population with mutation. For populations with less than 400 individuals, we assessed the impact of the rates of asexuality on the full exact distributions of F _IS, the probabilities of positive and negative F _IS, the probabilities of fixation and the probabilities to observe changes in the sign of F _IS over one generation. After an infinite number of generations, we distinguished three main patterns of effects of the rates of asexuality on genetic diversity that also varied according to the interactions of mutation and genetic drift. Even rare asexual events in mainly sexual populations impacted the balance between negative and positive F _IS and the occurrence of extreme values. It also drastically modified the probability to change the sign of F _IS value at one locus over one generation. When mutation prevailed over genetic drift, increasing rates of asexuality continuously increased the variance of F _IS that reached its highest value in fully asexual populations. In consequence, even ancient asexual populations showed the entire F _IS spectrum, including strong positive F _IS. The prevalence of heterozygous loci only occurred in full asexual populations when genetic drift dominated.     

Somatic Mutation Favors the Evolution of Diploidy

Explanations of diploidy have focused on advantages gained from masking deleterious mutations that are inherited. Recent theory has shown that these explanations are flawed. Indeed, we still lack any satisfactory explanation of diploidy in species that are asexual or that recombine only rarely. Here I consider a possibility first suggested by EFROIMSON in 1932, by MULLER in 1964 and by CROW and KIMURA in 1965: diploidy may provide protection against somatic, not inherited, mutations. I both compare the mean fitness of haploid and diploid populations that are asexual and investigate the invasion of ``diploidy' alleles in sexual populations. When deleterious mutations are partially recessive and somatic mutation is sufficiently common, somatic mutation provides a clear advantage to diploidy in both asexual and sexual species.