Muller's Ratchet Research Articles

Quantifying the threat of extinction from Muller's ratchet in the diploid Amazon molly (Poecilia formosa).

BackgroundThe Amazon molly (Poecilia formosa) is a small unisexual fish that has been suspected of being threatened by extinction from the stochastic accumulation of slightly deleterious mutations that is caused by Muller's ratchet in non-recombining populations. However, no detailed quantification of the extent of this threat is available.ResultsHere we quantify genomic decay in this fish by using a simple model of Muller's ratchet with the most realistic parameter combinations available employing the evolution@home global computing system. We also describe simple extensions of the standard model of Muller's ratchet that allow us to deal with selfing diploids, triploids and mitotic recombination. We show that Muller's ratchet creates a threat of extinction for the Amazon molly for many biologically realistic parameter combinations. In most cases, extinction is expected to occur within a time frame that is less than previous estimates of the age of the species, leading to a genomic decay paradox.ConclusionHow then does the Amazon molly survive? Several biological processes could individually or in combination solve this genomic decay paradox, including paternal leakage of undamaged DNA from sexual sister species, compensatory mutations and many others. More research is needed to quantify the contribution of these potential solutions towards the survival of the Amazon molly and other (ancient) asexual species.

Muller's Ratchet and compensatory mutation in Caenorhabditis briggsae mitochondrial genome evolution

BackgroundThe 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.ResultsWe characterized mitochondrial genome evolutionary processes in Caenorhabditis briggsae natural isolates to show that numerous lineages experience a high incidence of nonsynonymous substitutions in protein-coding genes and accumulate unusual deleterious noncoding DNA stretches with associated heteroplasmic function-disrupting genome deletions. Isolate-specific deletion proportions correlated negatively with nematode fecundity, suggesting that these deletions might negatively affect C. briggsae fitness. However, putative compensatory mutations were also observed that are predicted to reduce heteroplasmy levels of deleterious deletions. Paradoxically, compensatory mutations were observed in one major intraspecific C. briggsae clade where population sizes are estimated to be very small (and selection is predicted to be relatively weak), but not in a second major clade where population size estimates are much larger and selection is expected to be more efficient.ConclusionThis study provides evidence that the mitochondrial genomes of animals evolving in nature are susceptible to Muller's Ratchet, suggests that context-dependent compensatory mutations can accumulate in small populations, and predicts that Muller's Ratchet can affect fundamental evolutionary forces such as the rate of mutation.

On the potential for extinction by Muller's Ratchet in Caenorhabditis elegans

BackgroundThe self-fertile hermaphrodite worm C. elegans is an important model organism for biology, yet little is known about the origin and persistence of the self-fertilizing mode of reproduction in this lineage. Recent work has demonstrated an extraordinary degree of selfing combined with a high deleterious mutation rate in contemporary populations. These observations raise the question as to whether the mutation load might rise to such a degree as to eventually threaten the species with extinction. The potential for such a process to occur would inform our understanding of the time since the origin of self-fertilization in C. elegans history.ResultsTo address this issue, here we quantify the rate of fitness decline expected to occur via Muller's ratchet for a purely selfing population, using both analytical approximations and globally distributed individual-based simulations from the evolution@home system to compute the rate of deleterious mutation accumulation. Using the best available estimates for parameters of how C. elegans evolves, we conclude that pure selfing can persist for only short evolutionary intervals, and is expected to lead to extinction within thousands of years for a plausible portion of parameter space. Credible lower-bound estimates of nuclear mutation rates do not extend the expected time to extinction much beyond a million years.ConclusionThus we conclude that either the extreme self-fertilization implied by current patterns of genetic variation in C. elegans arose relatively recently or that low levels of outcrossing and other factors are key to the persistence of C. elegans into the present day. We also discuss results for the mitochondrial genome and the implications for C. briggsae, a close relative that made the transition to selfing independently of C. elegans.

The traveling-wave approach to asexual evolution: Muller's ratchet and speed of adaptation

We use traveling-wave theory to derive expressions for the rate of accumulation of deleterious mutations under Muller's ratchet and the speed of adaptation under positive selection in asexual populations. Traveling-wave theory is a semi-deterministic description of an evolving population, where the bulk of the population is modeled using deterministic equations, but the class of the highest-fitness genotypes, whose evolution over time determines loss or gain of fitness in the population, is given proper stochastic treatment. We derive improved methods to model the highest-fitness class (the stochastic edge) for both Muller's ratchet and adaptive evolution, and calculate analytic correction terms that compensate for inaccuracies which arise when treating discrete fitness classes as a continuum. We show that traveling-wave theory makes excellent predictions for the rate of mutation accumulation in the case of Muller's ratchet, and makes good predictions for the speed of adaptation in a very broad parameter range. We predict the adaptation rate to grow logarithmically in the population size until the population size is extremely large.

Mutational Interference and the Progression of Muller's Ratchet When Mutations Have a Broad Range of Deleterious Effects

Deleterious mutations can accumulate in asexual haploid genomes through the process known as Muller's ratchet. This process has been described in the literature mostly for the case where all mutations are assumed to have the same effect on fitness. In the more realistic situation, deleterious mutations will affect fitness with a wide range of effects, from almost neutral to lethal. To elucidate the behavior of the ratchet in this more realistic case, simulations were carried out in a number of models, one where all mutations have the same effect on selection [one-dimensional (1D) model], one where the deleterious mutations can be divided into two groups with different selective effects [two-dimensional (2D) model], and finally one where the deleterious effects are distributed. The behavior of these models suggests that deleterious mutations can be classified into three different categories, such that the behavior of each can be described in a straightforward way. This makes it possible to predict the ratchet rate for an arbitrary distribution of fitness effects using the results for the well-studied 1D model with a single selection coefficient. The description was tested and shown to work well in simulations where selection coefficients are derived from an exponential distribution.

Gene Co-Inheritance and Gene Transfer

Functional transfer of mitochondrial genes to the nucleus is very common in some taxa but entirely lacking in others. Current evolutionary theories to account for this variation predict that outcrossing, which allows escape from Muller's ratchet and faster spread of beneficial mutations, should favor gene transfer. We find that functional gene transfer is more common in selfing or clonal plants than in outcrossing plants, a pattern opposite to prediction. We suggest that reproductive modes, such as selfing and vegetative reproduction, conserve adaptive mitonuclear gene combinations, allowing functional transfer, whereas outcrossing prevents transfer by breaking up these combinations.

Fitness Declines in Tobacco Etch Virus upon Serial Bottleneck Transfers

It has been well established that populations of RNA viruses transmitted throughout serial bottlenecks suffer from significant fitness declines as a consequence of the accumulation of deleterious mutations by the onset of Muller's ratchet. Bottlenecks are unavoidably linked to different steps of the infectious cycle of most plant RNA viruses, such as vector-mediated transmissions and systemic colonization of new leaves. Here we report evidence for fitness declines by the accumulation of deleterious mutations in the potyvirus Tobacco etch virus (TEV). TEV was inoculated into the nonsystemic host Chenopodium quinoa, and local lesions were isolated and used to initiate 20 independent mutation accumulation lineages. Weekly, a random lesion from each lineage was isolated and used to inoculate the next set of plants. At each transfer, the Malthusian growth rate was estimated. After 11 consecutive transfers, all lineages suffered significant fitness losses, and one even became extinct. The average rate of fitness decline was 5% per day. The average pattern of fitness decline was consistent with antagonistic epistasis between deleterious mutations, as postulated for antiredundant genomes. Temporal fitness fluctuations were not explained by random noise but reflected more complex underlying processes related to emergence and self-organization phenomena.

Small-world networks decrease the speed of Muller's ratchet

Muller's ratchet is an evolutionary process that has been implicated in the extinction of asexual species, the evolution of non-recombining genomes, such as the mitochondria, the degeneration of the Y chromosome, and the evolution of sex and recombination. Here we study the speed of Muller's ratchet in a spatially structured population which is subdivided into many small populations (demes) connected by migration, and distributed on a graph. We studied different types of networks: regular networks (similar to the stepping-stone model), small-world networks and completely random graphs. We show that at the onset of the small-world network - which is characterized by high local connectivity among the demes but low average path length - the speed of the ratchet starts to decrease dramatically. This result is independent of the number of demes considered, but is more pronounced the larger the network and the stronger the deleterious effect of mutations. Furthermore, although the ratchet slows down with increasing migration between demes, the observed decrease in speed is smaller in the stepping-stone model than in small-world networks. As migration rate increases, the structured populations approach, but never reach, the result in the corresponding panmictic population with the same number of individuals. Since small-world networks have been shown to describe well the real contact networks among people, we discuss our results in the light of the evolution of microbes and disease epidemics.

Evolution@home: observations on participant choice, work unit variation and low‐effort global computing

AbstractMany simulation efforts in ecology and evolutionary biology employ individual‐based models that are well suited for including many biological details. These models often pose serious computational challenges if all biologically interesting parameter combinations are to be explored. The challenges are even greater for biologists who often lack supercomputing facilities and the manpower for implementing complex global computing systems such as SETI@home. Under such limiting conditions, evolution@home started as a one‐man effort to distribute simulations of Muller's ratchet to Internet‐connected computers of participants from the general public. This paper addresses experiences in low‐effort global computing made with evolution@home over more than four years. It shows how allowing participants to choose the class of computational complexity they want to contribute to can help to deal with the bewildering variety of computational complexities that easily result from individual‐based models. Results suggest that, as a first rough approximation, participants' complexity choices are distributed surprisingly even over all reasonable classes of CPU‐time and RAM requirements. More often than not, participants tend to finish the simulations they start, if they are committed enough to submit any results at all. Potential uses of intermediate simulation results are discussed and the error of magnitude is introduced to help to deal with imprecise CPU‐time predictions. Experiences with the choices of over 300 users who have contributed more than 100 000 simulations with a total of over 80 years CPU time are reviewed. Copyright © 2007 John Wiley & Sons, Ltd.

Muller’s ratchet in random graphs and scale-free networks

Muller's ratchet is an evolutionary process that has been implicated in the extinction of asexual species, the evolution of mitochondria, the degeneration of the Y chromosome, the evolution of sex and recombination and the evolution of microbes. Here we study the speed of Muller's ratchet in a population subdivided into many small subpopulations connected by migration, and distributed on a network. We compare the speed of the ratchet in two distinct types of topologies: scale free networks and random graphs. The difference between the topologies is noticeable when the average connectivity of the network and the migration rate is large. In this situation we observe that the ratchet clicks faster in scale free networks than in random graphs. So contrary to intuition, scale free networks are more prone to loss of genetic information than random graphs. On the other hand, we show that scale free networks are more robust to the random extinction than random graphs. Since these complex networks have been shown to describe well real-life systems, our results open a framework for studying the evolution of microbes and disease epidemics.

Hemiclonal reproduction slows down the speed of Muller's ratchet in the hybridogenetic frog Rana esculenta

Rare recombination in otherwise asexually reproducing organisms is known to beneficially influence the fitness in small populations. In most of the investigated organisms, asexual and rare sexual generations with recombination follow each other sequentially. Here we present a case where clonal reproduction and rare recombination occur simultaneously in the same population. The hybridogenetic water frog Rana esculenta (E), a hybrid between R. lessonae (L) and R. ridibunda (R) produces gametes that only contain the unaltered maternal R part of their genome. New generations of R. esculenta usually arise from E x L matings. Intraspecific E x E matings produce mostly inviable offspring, but in rare cases, female R. ridibunda arise from such matings which are capable of recombination. In the absence of conspecific males, these R females have to mate with E males, which results in further R females, or with L males, which produces new E lineages. This indirect mechanism reintroduces recombination into the otherwise clonally transmitted R genomes in R. esculenta populations. In this study, we show through Monte Carlo simulations that, in most cases, it is sufficient that only between 1 % and 10 % of mixed water frog populations consist of R females to prevent or significantly reduce the fixation and accumulation of deleterious mutations.

Interference among deleterious mutations favours sex and recombination in finite populations

Sex and recombination are widespread, but explaining these phenomena has been one of the most difficult problems in evolutionary biology. Recombination is advantageous when different individuals in a population carry different advantageous alleles. By bringing together advantageous alleles onto the same chromosome, recombination speeds up the process of adaptation and opposes the fixation of harmful mutations by means of Muller's ratchet. Nevertheless, adaptive substitutions favour sex and recombination only if the rate of adaptive mutation is high, and Muller's ratchet operates only in small or asexual populations. Here, by tracking the fate of modifier alleles that alter the frequency of sex and recombination, we show that background selection against deleterious mutant alleles provides a stochastic advantage to sex and recombination that increases with population size. The advantage arises because, with low levels of recombination, selection at other loci severely reduces the effective population size and genetic variance in fitness at a focal locus (the Hill-Robertson effect), making a population less able to respond to selection and to rid itself of deleterious mutations. Sex and recombination reveal the hidden genetic variance in fitness by combining chromosomes of intermediate fitness to create chromosomes that are relatively free of (or are loaded with) deleterious mutations. This increase in genetic variance within finite populations improves the response to selection and generates a substantial advantage to sex and recombination that is fairly insensitive to the form of epistatic interactions between deleterious alleles. The mechanism supported by our results offers a robust and broadly applicable explanation for the evolutionary advantage of recombination and can explain the spread of costly sex.

Muller’s ratchet in symbiont populations

Muller's ratchet, the inevitable accumulation of deleterious mutations in asexual populations, has been proposed as a major factor in genome degradation of obligate symbiont organisms. Essentially, if left unchecked the ratchet will with certainty cause extinction due to the ever increasing mutational load. This paper examines the evolutionary fate of insect symbionts, using mathematical modelling to simulate the accumulation of deleterious mutations. We investigate the effects of a hierarchical two level population structure. Since each host contains its own subpopulation of symbionts, there will be a large number of small symbiont populations linked indirectly via selection on the host level. We show that although the separate subpopulations will accumulate deleterious mutations quickly, the symbiont population as a whole will be protected from extinction by selection acting on the hosts. As a consequence, the extent of genome degradation observed in present day symbionts is more likely to represent loss of functions that were (near-) neutral to the host, rather than a snap shot of a decline towards complete genetic collapse.

The ecological distribution of reproductive mode in oribatid mites, as related to biological complexity

The high incidence of asexuality in oribatid mites presents an unusual opportunity for examining hypotheses for the maintenance of sex. There is a presumed range in age of asexual species: many oribatid species are phylogenetically clustered, occurring in speciose early-derivative families or genera without sexual species, while others are phylogenetically isolated from other asexual species, occurring in later derivative taxa with sexual congeners. We examined the distribution of oribatid mite reproductive mode in soil of corn fields, grassy and shrub fields, and forests in central New York State (three replicate plots of each type, with 25 samples per plot), to test three ecological predictions from current theory. (1) If overall biotic uncertainty, as generated by competitors and predators, mediates the ecological distribution of oribatid mites, then the proportion of asexual oribatid mites should be negatively correlated with biological diversity; we examine this prediction using literature data as well. (2) If Muller's Ratchet (the stochastic loss of best genotypes, which is independent of environment), mediates the success of asexuality, then no ecological pattern should exist. (3) If general purpose genotypes are characteristic of asexual oribatid mites, their habitat distribution should be broader than that of sexual species. For each plot the level of asexuality was compared to indices of overall biotic diversity, as calculated from the pooled oribatid mite (competitors) and mesostigmatid mite (predator) communities. We found no negative correlation in this relationship in our own data or in the literature analysis of 290 faunal surveys from 50 literature sources, so we reject biotic uncertainty as an important determinant of reproductive mode distribution. When only data on phylogenetically clustered asexuals are considered, there is instead a positive correlation between asexuality and diversity that is not explained. Because of the latter pattern we tentatively reject Muller's Ratchet as the primary factor maintaining reproductive mode in these mites, but cannot reject it for isolated asexual species. Niche breadth in sexual and asexual oribatid mites provides no support for widespread general purpose genotypes but broad patterns in the literature suggest that the idea needs further investigation. Possible complicating or unknown factors that are discussed include historical disturbance in the study area, the relationship between parasitism and general biotic diversity, and the level and source of genetic diversity in asexual oribatid mites.

Quantifying the genomic decay paradox due to Muller's ratchet in human mitochondrial DNA

The observation of high mitochondrial mutation rates in human pedigrees has led to the question of how such an asexual genetic system can survive the accumulation of slightly deleterious mutations caused by Muller's ratchet. I define a null model to quantify in unprecedented detail the threat from extinction caused by Muller's ratchet. This model is general enough to explore the biological significance of Muller's ratchet in various species where its operation has been suspected. For increased precision over a wide range of parameter space I employ individual-based simulations run by evolution@home, the first global computing system for evolutionary biology. After compiling realistic values for the key parameters in human mitochondrial DNA (mtDNA) I find that a surprisingly large range of biologically realistic parameter combinations would lead to the extinction of the human line over a period of 20 million years - if accepted wisdom about mtDNA and Muller's ratchet is correct. The resulting genomic decay paradox complements a similar threat from extinction due to mutation accumulation in nuclear DNA and suggests evaluation of unconventional explanations for long-term persistence. A substantial list of potential solutions is given, including compensatory back mutations, mutation rate heterogeneity and occasional recombination in mtDNA. Future work will have to explore which of these actually solves the paradox. Nonetheless, the results presented here provide yet another reason to minimize anthropogenic increase of mutation rates.

Fixation of advantageous mutations in an off-equilibrium population

We investigate the evolution of asexual populations subject to a large supply of deleterious mutations such that Muller's ratchet operates. In this regime, the accumulation of deleterious mutations takes place continuously with the resulting loss of the least-loaded class of individuals. In the current work, we study the effect of the supply of beneficial mutations on the ratchet's speed. We also examine how the rate of substitution of favorable mutations as well as the mean selective effect of favorable mutations that reach fixation is compared to those assuming a population at equilibrium. We observe that under Muller's ratchet, the rate of fixation of advantageous mutations is higher than that predicted for an equilibrium population. The difference between the rate supposing an equilibrium regime and that for the non-equilibrium case becomes larger as we increase the rate of deleterious mutations. On the other hand, the mean selective effect of beneficial mutations that reach fixation is smaller than the expected value for the equilibrium situation.

Elimination of deleterious mutations in plastid genomes by gene conversion

Asexual reproduction is believed to be detrimental, mainly because of the accumulation of deleterious mutations over time, a hypothesis known as Muller's ratchet. In seed plants, most asexually reproducing genetic systems are polyploid, with apomictic species (plants forming seeds without fertilization) as well as plastids and mitochondria providing prominent examples. Whether or not polyploidy helps asexual genetic systems to escape Muller's ratchet is unknown. Gene conversion, particularly when slightly biased, represents a potential mechanism that could allow asexual genetic systems to reduce their mutation load in a genome copy number-dependent manner. However, direct experimental evidence for the operation of gene conversion between genome molecules to correct mutations is largely lacking. Here we describe an experimental system based on transgenic tobacco chloroplasts that allows us to analyze gene conversion events in higher plant plastid genomes. We provide evidence for gene conversion acting as a highly efficient mechanism by which the polyploid plastid genetic system can correct deleterious mutations and make one good genome out of two bad ones. Our finding that gene conversion can be biased may provide a molecular link between asexual reproduction, high genome copy numbers and low mutation rates.

The Complete Mitochondrial Genome of the Entomopathogenic Nematode Steinernema carpocapsae: Insights into Nematode Mitochondrial DNA Evolution and Phylogeny

We determined the complete sequence of the mitochondrial DNA of the entomopathogenic nematode Steinernema carpocapsae and analyzed its structure and composition as well as the secondary structures predicted for its tRNAs and rRNAs. Almost the complete genome has been amplified in one fragment with long PCR and sequenced using a shotgun strategy. The 13,925-bp genome contains genes for 2 rRNAs, 22 tRNAs, and 12 proteins and lacks an ORF encoding ATPase subunit 8. Four initiation codons were inferred, TTT, TTA, ATA, and ATT, most of the genes ended with TAA or TAG, and only two had a T as an incomplete stop codon. All predicted tRNAs showed the nonconventional secondary structure typical of Secernentea. Although we were able to fold the sequences of trnN, trnD, and trnC into more conventional cloverleaf structures after adding adjacent nucleotides, northern blot experiments showed that the nonstandard tRNAs are actually expressed. Phylogenetic and comparative analyses showed that the mitochondrial genome of S. carpocapsae is more closely related to the genomes of A. suum and C. elegans than to that of Strongyloides stercoralis. This finding does not support the phylogeny based on nuclear small subunit ribosomal DNA sequences previously published. This discrepancy may result from differential reproductive strategies and/or differential selective pressure acting on nuclear and mitochondrial genes. The distinctive characteristics observed among mitochondrial genomes of Secernentea may have arisen to counteract the deleterious effects of Muller's ratchet, which is probably enhanced by the reproductive strategies and selective pressures referred to above.

Fast Accumulation of Nonsynonymous Mutations on the Female-Specific W Chromosome in Birds

Following cessation of recombination during sex chromosome evolution, the nonrecombining sex chromosome is affected by a number of degenerative forces, possibly resulting in the fixation of deleterious mutations. This might take place because of weak selection against recessive or partly recessive deleterious mutations due to permanent heterozygosity of nonrecombining chromosomes. Furthermore, population genetic processes, such as selective sweeps, background selection, and Muller's ratchet, result in a reduction in Ne, which increase the likelihood of fixation of deleterious mutations. Theory thus predicts that nonrecombining genes should show increased levels of nonsynonymous (dN) to synonymous substitutions (dS). We tested this in an avian system by estimating the ratio between dN and dS in six gametologous gene pairs located on the Z chromosome and the nonrecombining, female-specific W chromosome. In comparisons, we found a significantly higher dN/dS ratio for the W-linked than the Z-linked copy in three of the investigated genes. In a concatenated alignment of all six genes, the dN/dS ratio was six times higher for W-linked than Z-linked genes. By using human and mouse as outgroup in maximum likelihood analyses, W-linked genes were found to evolve differently compared with their Z-linked gametologues and outgroup sequences. This seems not to be a consequence of functional diversification because d(N)/d(S) ratios between gametologous gene copies were consistently low. We conclude that deleterious mutations are accumulating at a high rate on the avian W chromosome, probably as a result of the lack of recombination in this female-specific chromosome.

Extreme Population Structure and High Interspecific Divergence of the Silene Y Chromosome

Previous studies have demonstrated that the diversity of Y-linked genes is substantially lower than that of their X-linked homologs in the plant Silene latifolia. This difference has been attributed to selective sweeps, Muller's ratchet, and background selection, processes that are predicted to severely affect the evolution of the nonrecombining Y chromosome. We studied the DNA diversity of a noncoding region of the homologous genes DD44Y and DD44X, sampling S. latifolia populations from a wide geographical area and also including the closely related species S. dioica, S. diclinis, and S. heuffelii. On the Y chromosome of S. latifolia, we found substantial DNA diversity. Geographical population structure was far higher than on the X chromosome and differentiation between the species was also higher for the Y than for the X chromosome. Our findings indicate that the loss of genetic diversity on the Y chromosome in Silene occurs within local populations rather than within entire species. These results are compatible with background selection, Muller's ratchet, and local selective sweeps, but not with species-wide selective sweeps. The higher interspecific divergence of DD44Y, compared to DD44X, supports the hypothesis that Y chromosome differentiation between incipient species precedes reproductive isolation of the entire genome, forming an early stage in the process of speciation.