Recombination and the immortality of the germ line

Asexual populations irreversibly accumulate mildly deleterious mutations through the occasional stochastic loss of their least-loaded line, a process known as “Muller's Ratchet”. This paper explores the dynamics of this process, and the role of recombination in halting the Ratchet. Simulation studies show that an optimal class comprising n_o individuals is lost in about 10n_o generations, implying that adaptedness may deteriorate rather rapidly in geological time. Asexual organisms will persist only if they are very numerous, or if they have very small genomes, or if there is extensive negative interaction among nonallelic mutations. Otherwise, long-term persistence requires that unloaded genomes be continually generated by recombination. An approximate expression for the rate of recombination needed to halt the Ratchet is developed, and shows that substantial recombination is necessary in populations of fewer than about 10¹⁰ individuals. A further complication is introduced by mutations in sequences which specify proofreading enzymes. Since these will reduce the fidelity of their own replication, a process of positive feedback leading to an ever-accelerating loss of function is conceivable.     

QUANTITATIVE VARIATION IN FINITE PARTHENOGENETIC POPULATIONS: WHAT STOPS MULLER'S RATCHET IN THE ABSENCE OF RECOMBINATION?

Finite parthenogenetic populations with high genomic mutation rates accumulate deleterious mutations if back mutations are rare. This mechanism, known as Muller's ratchet, can explain the rarity of parthenogenetic species among so called higher organisms. However, estimates of genomic mutation rates for deleterious alleles and their average effect in the diploid condition in Drosophila suggest that Muller's ratchet should eliminate parthenogenetic insect populations within several hundred generations, provided all mutations are unconditionally deleterious. This fact is inconsistent with the existence of obligatory parthenogenetic insect species. In this paper an analysis of the extent to which compensatory mutations can counter Muller's ratchet is presented. Compensatory mutations are defined as all mutations that compensate for the phenotypic effects of a deleterious mutation. In the case of quantitative traits under stabilizing selection, the rate of compensatory mutations is easily predicted. It is shown that there is a strong analogy between the Muller's ratchet model of Felsenstein (1974) and the quantitative genetic model considered here, except for the frequency of compensatory mutations. If the intensity of stabilizing selection is too small or the mutation rate too high, the optimal genotype becomes extinct and the population mean drifts from the optimum but still reaches a stationary distribution. This distance is essentially the same as predicted for sexually reproducing populations under the same circumstances. Hence, at least in the short run, compensatory mutations for quantitative characters are as effective as recombination in halting the decline of mean fitness otherwise caused by Muller's ratchet. However, it is questionable whether compensatory mutations can prevent Muller's ratchet in the long run because there might be a limit to the capacity of the genome to provide compensatory mutations without eliminating deleterious mutations at least during occasional episodes of sex.     

The role of pleiotropy in the maintenance of sex in yeast

In facultatively sexual species, lineages that reproduce asexually for a period of time can accumulate mutations that reduce their ability to undergo sexual reproduction when sex is favorable. We propagated Saccharomyces cerevisiae asexually for approximately 800 generations, after which we measured the change in sexual fitness, measured as the proportion of asci observed in sporulation medium. The sporulation rate in cultures propagated asexually at small population size declined by 8%, on average, over this time period, indicating that the majority of mutations that affect sporulation rate are deleterious. Interestingly, the sporulation rate in cultures propagated asexually at large population size improved by 11%, on average, indicating that selection on asexual function effectively eliminated most of the mutations deleterious to sporulation ability. These results suggest that pleiotropy between mutations' effects on asexual fitness and sexual fitness was predominantly positive, at least for the mutations accumulated in this experimental evolution study. A positive correlation between growth rate and sporulation rate among lines also provided evidence for positive pleiotropy. These results demonstrate that, at least under certain circumstances, selection acting on asexual fitness can help to maintain sexual function.     

The Ratchet and the Red Queen: the maintenance of sex in parasites

The adaptive significance of sexual reproduction remains as an unsolved problem in evolutionary biology. One promising hypothesis is that frequency‐dependent selection by parasites selects for sexual reproduction in hosts, but it is unclear whether such selection on hosts would feed back to select for sexual reproduction in parasites. Here we used individual‐based computer simulations to explore this possibility. Specifically, we tracked the dynamics of asexual parasites following their introduction into sexual parasite populations for different combinations of parasite virulence and transmission. Our results suggest that coevolutionary interactions with hosts would generally lead to a stable coexistence between sexual parasites and a single parasite clone. However, if multiple mutations to asexual reproduction were allowed, we found that the interaction led to the accumulation of clonal diversity in the asexual parasite population, which led to the eventual extinction of the sexual parasites. Thus, coevolution with sexual hosts may not be generally sufficient to select for sex in parasites. We then allowed for the stochastic accumulation of mutations in the finite parasite populations (Muller's Ratchet). We found that, for higher levels of parasite virulence and transmission, the population bottlenecks resulting from host–parasite coevolution led to the rapid accumulation of mutations in the clonal parasites and their elimination from the population. This result may explain the observation that sexual reproduction is more common in parasitic animals than in their free‐living relatives.     

No evidence for accumulation of deleterious mutations and fitness degradation in clonal fish hybrids: Abandoning sex without regrets

Despite its inherent costs, sexual reproduction is ubiquitous in nature, and the mechanisms to protect it from a competitive displacement by asexuality remain unclear. Popular mutation‐based explanations, like the Muller's ratchet and the Kondrashov's hatchet, assume that purifying selection may not halt the accumulation of deleterious mutations in the nonrecombining genomes, ultimately leading to their degeneration. However, empirical evidence is scarce and it remains particularly unclear whether mutational degradation proceeds fast enough to ensure the decay of clonal organisms and to prevent them from outcompeting their sexual counterparts. To test this hypothesis, we jointly analysed the exome sequences and the fitness‐related phenotypic traits of the sexually reproducing fish species and their clonal hybrids, whose evolutionary ages ranged from F1 generations to 300 ky. As expected, mutations tended to accumulate in the clonal genomes in a time‐dependent manner. However, contrary to the predictions, we found no trend towards increased nonsynonymity of mutations acquired by clones, nor higher radicality of their amino acid substitutions. Moreover, there was no evidence for fitness degeneration in the old clones compared with that in the younger ones. In summary, although an efficacy of purifying selection may still be reduced in the asexual genomes, our data indicate that its efficiency is not drastically decreased. Even the oldest investigated clone was found to be too young to suffer fitness consequences from a mutation accumulation. This suggests that mechanisms other than mutation accumulation may be needed to explain the competitive advantage of sex in the short term.     

SHOOT APICAL MERISTEMS AND MUTATION: STRATIFIED MERISTEMS AND ANGIOSPERM EVOLUTION

Although apical meristems with a tunica-corpus organization occur in some gymnosperms and in practically all angiosperms, the adaptive significance of such meristems is unknown. Mathematical modeling and computer simulation studies have shown that such stratified meristems promote the long-term retention of many categories of somatic mutation (selectively advantageous, neutral, and disadvantageous). These mutations are maintained primarily as periclinal chimeras. The individual component meristems of a stratified apex have relatively small populations of apical initials. Thus, in long-lived genets, the individual component meristems of the stratified meristems of the ramets would be expected to accumulate mutations due to the operation of Muller's Ratchet. In angiosperms the accumulation of mutants and the associated loss in reproductive capacity (sexual) is compensated for by developmental selection that promotes the loss of defective genotypes without proportionate losses in reproductive capacity.     

Beneficial mutation selection balance and the effect of linkage on positive selection

When beneficial mutations are rare, they accumulate by a series of selective sweeps. But when they are common, many beneficial mutations will occur before any can fix, so there will be many different mutant lineages in the population concurrently. In an asexual population, these different mutant lineages interfere and not all can fix simultaneously. In addition, further beneficial mutations can accumulate in mutant lineages while these are still a minority of the population. In this article, we analyze the dynamics of such multiple mutations and the interplay between multiple mutations and interference between clones. These result in substantial variation in fitness accumulating within a single asexual population. The amount of variation is determined by a balance between selection, which destroys variation, and beneficial mutations, which create more. The behavior depends in a subtle way on the population parameters: the population size, the beneficial mutation rate, and the distribution of the fitness increments of the potential beneficial mutations. The mutation-selection balance leads to a continually evolving population with a steady-state fitness variation. This variation increases logarithmically with both population size and mutation rate and sets the rate at which the population accumulates beneficial mutations, which thus also grows only logarithmically with population size and mutation rate. These results imply that mutator phenotypes are less effective in larger asexual populations. They also have consequences for the advantages (or disadvantages) of sex via the Fisher-Muller effect; these are discussed briefly.     

THE CONTRIBUTION OF NEW MUTATIONS TO GENOTYPE-ENVIRONMENT INTERACTION FOR FITNESS IN DROSOPHILA MELANOGASTER

Many studies have documented the existence of genotype-environment interaction (GEI) for traits closely related to fitness in natural populations. A type of GEI that is commonly observed is changes in the fitness ranking of genetic groups (families, clones, or inbred lines) in different environments. We refer to such changes in ranking as crossing of reaction norms for fitness. A common interpretation of crossing of reaction norms for fitness is that selection favors different alleles in the different environments (i.e., that “trade-offs” exist). If this is the case, selection could maintain genetic variation, and even lead to reproductive isolation between subpopulations using different environments. Even if the same alleles are favored in every environment, however, deleterious mutations that vary in the magnitude of their effect depending on environment could cause reaction norms for fitness to cross. If deleterious mutations with environment-dependent effects are responsible for maintaining much of the variation leading to crossing of reaction norms for fitness in natural populations, it should be possible to observe crossing of reaction norms for fitness among otherwise genetically identical lines bearing newly arisen spontaneous mutations. We examined the contribution of new mutations to GEI for fitness in Drosophila melanogaster. Eighteen lines were derived from a common, highly inbred base stock, and maintained at a population size of 10 pairs for over 200 generations, to allow them to accumulate spontaneous mutations. Because of the small population size of the lines, selection against mildly deleterious mutations should have been relatively ineffective. The lines were tested for productivity (number of surviving adult progeny from a standard number of parents) in five different environmental treatments, comprising different food media, temperatures, and levels of competition. The lines showed highly significant GEI for productivity, owing largely to considerable changes in ranking in the different environments. We conclude that mutations that are deleterious on average, but whose quantitative effects depend on environment, could be responsible for maintaining much of the variation leading to crossing of reaction norms for fitness that has been observed in samples of D. melanogaster from the wild.     

Muller's Ratchet and compensatory mutation in <Emphasis Type="Italic">Caenorhabditis briggsae</Emphasis> mitochondrial genome evolution

Background  

The theory of Muller' Ratchet predicts that small asexual populations are doomed to accumulate ever-increasing deleterious mutation loads as a consequence of the magnified power of genetic drift and mutation that accompanies small population size. Evidence for Muller's Ratchet and knowledge on its underlying molecular mechanisms, however, are lacking for natural populations.     

H.J. Muller's contributions to mutation research

H. J. Muller is best known for his Nobel Prize work on the induction of mutations by ionizing radiation. Geneticists are less familiar with his contributions to mutation and how he related the process of mutagenesis to the gene and distinguished gene mutations from other genetic and epigenetic events such as polyploidy, chromosome rearrangements, and position effects. The hallmark of Muller's contributions is his design of genetic stocks to solve genetic problems and allow experimentation to reveal new phenomena. In this review I relate Muller's personality to his teaching and research and present a history of Muller's ideas on mutation from his first days in Morgan's fly lab to his final thoughts on what became called “Muller's ratchet”, a term he did not get to enjoy because it was coined seven years after his death.     

Body size evolution in an old insect order: No evidence for Cope's Rule in spite of fitness benefits of large size

We integrate field data and phylogenetic comparative analyses to investigate causes of body size evolution and stasis in an old insect order: odonates (“dragonflies and damselflies”). Fossil evidence for “Cope's Rule” in odonates is weak or nonexistent since the last major extinction event 65 million years ago, yet selection studies show consistent positive selection for increased body size among adults. In particular, we find that large males in natural populations of the banded demoiselle (Calopteryx splendens) over several generations have consistent fitness benefits both in terms of survival and mating success. Additionally, there was no evidence for stabilizing or conflicting selection between fitness components within the adult life‐stage. This lack of stabilizing selection during the adult life‐stage was independently supported by a literature survey on different male and female fitness components from several odonate species. We did detect several significant body size shifts among extant taxa using comparative methods and a large new molecular phylogeny for odonates. We suggest that the lack of Cope's rule in odonates results from conflicting selection between fitness advantages of large adult size and costs of long larval development. We also discuss competing explanations for body size stasis in this insect group.     

Stabilizing selection,mutational bias,and the evolution of sex*

Stabilizing selection around a fixed phenotypic optimum is expected to disfavor sexual reproduction, since asexually reproducing organisms can maintain a higher fitness at equilibrium, while sex disrupts combinations of compensatory mutations. This conclusion rests on the assumption that mutational effects on phenotypic traits are unbiased, that is, mutation does not tend to push phenotypes in any particular direction. In this article, we consider a model of stabilizing selection acting on an arbitrary number of polygenic traits coded by bialellic loci, and show that mutational bias may greatly reduce the mean fitness of asexual populations compared with sexual ones in regimes where mutations have weak to moderate fitness effects. Indeed, mutation and drift tend to push the population mean phenotype away from the optimum, this effect being enhanced by the low effective population size of asexual populations. In a second part, we present results from individual‐based simulations showing that positive rates of sex are favored when mutational bias is present, while the population evolves toward complete asexuality in the absence of bias. We also present analytical (QLE) approximations for the selective forces acting on sex in terms of the effect of sex on the mean and variance in fitness among offspring.     

Fixation of new alleles and the extinction of small populations: drift load, beneficial alleles, and sexual selection

With a small effective population size, random genetic drift is more important than selection in determining the fate of new alleles. Small populations therefore accumulate deleterious mutations. Left unchecked, the effect of these fixed alleles is to reduce the reproductive capacity of a species, eventually to the point of extinction. New beneficial mutations, if fixed by selection, can restore some of this lost fitness. This paper derives the overall change in fitness due to fixation of new deleterious and beneficial alleles, as a function of the distribution of effects of new mutations and the effective population size. There is a critical effective size below which a population will on average decline in fitness, but above which beneficial mutations allow the population to persist. With reasonable estimates of the relevant parameters, this critical effective size is likely to be a few hundred. Furthermore, sexual selection can act to reduce the fixation probability of deleterious new mutations and increase the probability of fixing new beneficial mutations. Sexual selection can therefore reduce the risk of extinction of small populations.     

Population structure promotes the evolution of costly sex in artificial gene networks

We build on previous observations that Hill–Robertson interference generates an advantage of sex that, in structured populations, can be large enough to explain the evolutionary maintenance of costly sex. We employed a gene network model that explicitly incorporates interactions between genes. Mutations in the gene networks have variable effects that depend on the genetic background in which they appear. Consequently, our simulations include two costs of sex—recombination and migration loads—that were missing from previous studies of the evolution of costly sex. Our results suggest a critical role for population structure that lies in its ability to align the long‐ and short‐term advantages of sex. We show that the addition of population structure favored the evolution of sex by disproportionately decreasing the equilibrium mean fitness of asexual populations, primarily by increasing the strength of Muller's Ratchet. Population structure also increased the ability of the short‐term advantage of sex to counter the primary limit to the evolution of sex in the gene network model—recombination load. On the other hand, highly structured populations experienced migration load in the form of Dobzhansky–Muller incompatibilities, decreasing the effective rate of migration between demes and, consequently, accelerating the accumulation of drift load in the sexual populations.     

Mutators, population size, adaptive landscape and the adaptation of asexual populations of bacteria.

Selection of mutator alleles, increasing the mutation rate up to 10, 000-fold, has been observed during in vitro experimental evolution. This spread is ascribed to the hitchhiking of mutator alleles with favorable mutations, as demonstrated by a theoretical model using selective parameters corresponding to such experiments. Observations of unexpectedly high frequencies of mutators in natural isolates suggest that the same phenomenon could occur in the wild. But it remains questionable whether realistic in natura parameter values could also result in selection of mutators. In particular, the main parameters of adaptation, the size of the adapting population and the height and steepness of the adaptive peak characterizing adaptation, are very variable in nature. By simulation approach, we studied the effect of these parameters on the selection of mutators in asexual populations, assuming additive fitness. We show that the larger the population size, the more likely the fixation of mutator alleles. At a large population size, at least four adaptive mutations are needed for mutator fixation; moreover, under stronger selection stronger mutators are selected. We propose a model based on multiple mutations to illustrate how second-order selection can optimize population fitness when few favorable mutations are required for adaptation.     

NONADAPTIVE PROCESSES CAN CREATE THE APPEARANCE OF FACULTATIVE CHEATING IN MICROBES

Adaptations to social life may take the form of facultative cheating, in which organisms cooperate with genetically similar individuals but exploit others. Consistent with this possibility, many strains of social microbes like Myxococcus bacteria and Dictyostelium amoebae have equal fitness in single‐genotype social groups but outcompete other strains in mixed‐genotype groups. Here we show that these observations are also consistent with an alternative, nonadaptive scenario: kin selection‐mutation balance under local competition. Using simple mathematical models, we show that deleterious mutations that reduce competitiveness within social groups (growth rate, e.g.) without affecting group productivity can create fitness effects that are only expressed in the presence of other strains. In Myxococcus, mutations that delay sporulation may strongly reduce developmental competitiveness. Deleterious mutations are expected to accumulate when high levels of kin selection relatedness relax selection within groups. Interestingly, local resource competition can create nonzero “cost” and “benefit” terms in Hamilton's rule even in the absence of any cooperative trait. Our results show how deleterious mutations can play a significant role even in organisms with large populations and highlight the need to test evolutionary causes of social competition among microbes.     

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.     

SEX‐CHROMOSOME TURNOVERS INDUCED BY DELETERIOUS MUTATION LOAD

In sharp contrast with mammals and birds, many cold‐blooded vertebrates present homomorphic sex chromosomes. Empirical evidence supports a role for frequent turnovers, which replace nonrecombining sex chromosomes before they have time to decay. Three main mechanisms have been proposed for such turnovers, relying either on neutral processes, sex‐ratio selection, or intrinsic benefits of the new sex‐determining genes (due, e.g., to linkage with sexually antagonistic mutations). Here, we suggest an additional mechanism, arising from the load of deleterious mutations that accumulate on nonrecombining sex chromosomes. In the absence of dosage compensation, this load should progressively lower survival rate in the heterogametic sex. Turnovers should occur when this cost outweighs the benefits gained from any sexually antagonistic genes carried by the nonrecombining sex chromosome. We use individual‐based simulations of a Muller's ratchet process to test this prediction, and investigate how the relevant parameters (effective population size, strength and dominance of deleterious mutations, size of nonrecombining segment, and strength of sexually antagonistic selection) are expected to affect the rate of turnovers.     

The “balance” argument and the evolution of sex

The “balance” argument suggests that if sex were maladaptive at the individual level, it would be quickly lost from species with asexual/sexual alternation. Williams has suggested an “Aphid-Rotifer” model for such species. It has the following characteristics (a) parthenogenesis is favoured when the environment is stable (b) when the environment changes qualitatively, sex generates offspring with an increased fitness variance compared to parthenogenetic progeny (c) if selection is intense and sib competition occurs then sex is favoured. It is argued here that condition (b) is not essential to the model. An increased fitness variance may be generated by the recombination of unfavourable mutations when one or more of the following occur; (1) founder effects (2) inbreeding (3) haplo-diploidy (4) intra-male competition. Parthenogenesis sustains an advantage when selection is relaxed and the possession of mutations is not reflected in differences in fitness. Sex is favoured when selection is intense and fitness reflects the possession of unfavourable mutations.