The accumulation of deleterious mutations within the frozen niche variation hypothesis

The frozen niche variation hypothesis proposes that asexual clones exploit a fraction of a total resource niche available to the sexual population from which they arise. Differences in niche breadth may allow a period of coexistence between a sexual population and the faster reproducing asexual clones. Here, we model the longer term threat to the persistence of the sexual population from an accumulation of clonal diversity, balanced by the cost to the asexual population resulting from a faster rate of accumulation of deleterious mutations. We use Monte-Carlo simulations to quantify the interaction of niche breadth with accumulating deleterious mutations. These two mechanisms may act synergistically to prevent the extinction of the sexual population, given: (1) sufficient genetic variation, and consequently niche breadth, in the sexual population; (2) a relatively slow rate of accumulation of genetic diversity in the clonal population; (3) synergistic epistasis in the accumulation of deleterious mutations.     

The influence of deleterious mutations on adaptation in asexual populations

We study the dynamics of adaptation in asexual populations that undergo both beneficial and deleterious mutations. In particular, how the deleterious mutations affect the fixation of beneficial mutations was investigated. Using extensive Monte Carlo simulations, we find that in the "strong-selection weak mutation (SSWM)" regime or in the "clonal interference (CI)" regime, deleterious mutations rarely influence the distribution of "selection coefficients of the fixed mutations (SCFM)"; while in the "multiple mutations" regime, the accumulation of deleterious mutations would lead to a decrease in fitness significantly. We conclude that the effects of deleterious mutations on adaptation depend largely on the supply of beneficial mutations. And interestingly, the lowest adaptation rate occurs for a moderate value of selection coefficient of deleterious mutations.     

On the accumulation of deleterious mutations during range expansions

We investigate the effect of spatial range expansions on the evolution of fitness when beneficial and deleterious mutations cosegregate. We perform individual‐based simulations of 1D and 2D range expansions and complement them with analytical approximations for the evolution of mean fitness at the edge of the expansion. We find that deleterious mutations accumulate steadily on the wave front during range expansions, thus creating an expansion load. Reduced fitness due to the expansion load is not restricted to the wave front, but occurs over a large proportion of newly colonized habitats. The expansion load can persist and represent a major fraction of the total mutation load for thousands of generations after the expansion. The phenomenon of expansion load may explain growing evidence that populations that have recently expanded, including humans, show an excess of deleterious mutations. To test the predictions of our model, we analyse functional genetic diversity in humans and find patterns that are consistent with our model.     

The legacy of domestication: accumulation of deleterious mutations in the dog genome

Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The d(N)/d(S) ratio (omega) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill-Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.     

The accumulation of deleterious mutations in rice genomes: a hypothesis on the cost of domestication

The extent of molecular differentiation between domesticated animals or plants and their wild relatives is postulated to be small. The availability of the complete genome sequences of two subspecies of the Asian rice, Oryza sativa (indica and japonica) and their wild relatives have provided an unprecedented opportunity to study divergence following domestication. We observed significantly more amino acid substitutions during rice domestication than can be expected from a comparison among wild species. This excess is disproportionately larger for the more radical kinds of amino acid changes (e.g. Cys<-->Tyr). We estimate that approximately a quarter of the amino acid differences between rice cultivars are deleterious, not accountable by the relaxation of selective constraints. This excess is negatively correlated with the rate of recombination, suggesting that 'hitchhiking' has occurred. We hypothesize that during domestication artificial selection increased the frequency of many deleterious mutations.     

Modes of reproduction and the accumulation of deleterious mutations with multiplicative fitness effects

Mutational load depends not only on the number and nature of mutations but also on the reproductive mode. Traditionally, only a few specific reproductive modes are considered in the search of explanations for the maintenance of sex. There are, however, many alternatives. Including these may give radically different conclusions. The theory on deterministic deleterious mutations states that in large populations segregation and recombination may lead to a lower load of deleterious mutations, provided that there are synergistic interactions. Empirical research suggests that effects of deleterious mutations are often multiplicative. Such situations have largely been ignored in the literature, since recombination and segregation have no effect on mutation load in the absence of epistasis. However, this is true only when clonal reproduction and sexual reproduction with equal male and female ploidy are considered. We consider several alternative reproductive modes that are all known to occur in insects: arrhenotoky, paternal genome elimination, apomictic thelytoky, and automictic thelytoky with different cytological mechanisms to restore diploidy. We give a method that is based on probability-generating functions, which provides analytical and numerical results on the distributions of deleterious mutations. Using this, we show that segregation and recombination do make a difference. Furthermore, we prove that a modified form of Haldane's principle holds more generally for thelytokous reproduction. We discuss the implications of our results for evolutionary transitions between different reproductive modes in insects. Since the strength of Muller's ratchet is reduced considerably for several forms of automictic thelytoky, many of our results are expected to be also valid for initially small populations.     

Sex slows down the accumulation of deleterious mutations in the homothallic fungus Aspergillus nidulans

Coexistence of sexual and asexual reproduction within the same individual is an intriguing problem, especially when it concerns homothallic haplonts, like the fungus Aspergillus nidulans. In this fungus asexual and sexual offspring have largely identical genotypes. This genetic model organism is an ideal tool to measure possible fitness effects of sex (compared to asex) resulting from causes other than recombination. In this article we show that slightly deleterious mutations accumulate at a lower rate in the sexual pathway than in the asexual pathway. This secondary sex advantage may contribute to the persistence of sexual spores in this fungus. We propose that this advantage results from intra-organismal selection of the fittest gametes or zygotes, which is more stringent in the costly sexual pathway.     

The McDonald-Kreitman test and slightly deleterious mutations

It is possible to estimate the proportion of substitutions that are due to adaptive evolution using the numbers of silent and nonsilent polymorphisms and substitutions in a McDonald and Kreitman-type analysis. Unfortunately, this estimate of adaptive evolution is biased downward by the segregation of slightly deleterious mutations. It has been suggested that 1 way to cope with the effects of these slightly deleterious mutations is to remove low-frequency polymorphisms from the analysis. We investigate the performance of this method theoretically. We show that although removing low-frequency polymorphisms does indeed reduce the bias in the estimate of adaptive evolution, the estimate is always downwardly biased, often to the extent that one would not be able to detect adaptive evolution, even if it existed. The method is reasonably satisfactory, only if the rate of adaptive evolution is high and the distribution of fitness effects for slightly deleterious mutations is very leptokurtic. Our analysis suggests that adaptive evolution could be quite prevalent in humans (>8%) and still not be detectable using current methodologies. Our analysis also suggests that the level of adaptive evolution has probably been underestimated, possibly substantially, in both bacteria and Drosophila.     

The influence of habitat on the size distribution of groupers in the upper Florida Keys

Synopsis The influence of habitat on the size distribution of groupers was examined at sites in the middle and upper Florida Keys. Transects were used to quantify the size distribution of groupers at study sites. There were significant differences in the size distribution of groupers within and among reef community types related to differences in species composition and patch reef size. Groupers with a giant life-history style (Sullivan & de Garine 1994) were more abundant, but smaller, on inshore patch reefs than offshore reef community types. However, grouper species with a dwarf life-history style (Sullivan & de Garine 1994) showed an opposite pattern with a lower abundance, but larger size, inshore than offshore. The length category of groupers constituting the majority of individuals observed on patch reefs was inversely related to reef size. Graysby Epinephelus cruentatus were shown to recruit to deeper (15–20 m), low-relief habitats offshore. Several factors influenced the size distribution of groupers in the study sites including habitat type, spear-fishing, competition, predation, and recruitment.     

Characterization of deleterious mutations in outcrossing populations.

Deng and Lynch recently proposed estimating the rate and effects of deleterious genomic mutations from changes in the mean and genetic variance of fitness upon selfing/outcrossing in outcrossing/highly selfing populations. The utility of our original estimation approach is limited in outcrossing populations, since selfing may not always be feasible. Here we extend the approach to any form of inbreeding in outcrossing populations. By simulations, the statistical properties of the estimation under a common form of inbreeding (sib mating) are investigated under a range of biologically plausible situations. The efficiencies of different degrees of inbreeding and two different experimental designs of estimation are also investigated. We found that estimation using the total genetic variation in the inbred generation is generally more efficient than employing the genetic variation among the mean of inbred families, and that higher degree of inbreeding employed in experiments yields higher power for estimation. The simulation results of the magnitude and direction of estimation bias under variable or epistatic mutation effects may provide a basis for accurate inferences of deleterious mutations. Simulations accounting for environmental variance of fitness suggest that, under full-sib mating, our extension can achieve reasonably well an estimation with sample sizes of only approximately 2000-3000.     

Paternal sex in parthenogenetic planarians: a tool to investigate the accumulation of deleterious mutations

Clonally reproducing organisms are expected to accumulate slightly deleterious mutations, and this has been demonstrated in RNA viruses, bacteria and unicellular algae. In this paper we present evidence for increased embryo mortality in obligate parthenogenetic strains of the freshwater flatworm Schmidtea polychroa, possibly indicating the action of deleterious mutations. The inheritance of this fitness defect was tested by crossing parthenogens with sexuals. This is possible because both forms are simultaneous hermaphrodites that produce fertile sperm. The resulting sexual offspring showed significantly increased embryo mortality in comparison to offspring of a sexual × sexual cross. Alternatives to a mutation explanation of these results, like the degeneration of male traits in parthenogens, are being discussed. In conclusion, these results lend support to the hypothesis that sex is advantageous to a multicellular organism because it prevents the accumulation of deleterious mutations.     

The effects of deleterious mutations on evolution at linked sites

The process of evolution at a given site in the genome can be influenced by the action of selection at other sites, especially when these are closely linked to it. Such selection reduces the effective population size experienced by the site in question (the Hill-Robertson effect), reducing the level of variability and the efficacy of selection. In particular, deleterious variants are continually being produced by mutation and then eliminated by selection at sites throughout the genome. The resulting reduction in variability at linked neutral or nearly neutral sites can be predicted from the theory of background selection, which assumes that deleterious mutations have such large effects that their behavior in the population is effectively deterministic. More weakly selected mutations can accumulate by Muller's ratchet after a shutdown of recombination, as in an evolving Y chromosome. Many functionally significant sites are probably so weakly selected that Hill-Robertson interference undermines the effective strength of selection upon them, when recombination is rare or absent. This leads to large departures from deterministic equilibrium and smaller effects on linked neutral sites than under background selection or Muller's ratchet. Evidence is discussed that is consistent with the action of these processes in shaping genome-wide patterns of variation and evolution.     

The role of deleterious mutations in allopatric speciation

Allopatric speciation is often assumed to occur as a consequence of adaptive divergence between two isolated populations. However, there are some scenarios in which reproductive isolation can be favored due to accumulated unconditionally deleterious mutations. If deleterious mutations have synergistic epistatic effects, it is shown here that the average fitness of recombinants between two parental lines with a given number of fixed mutations is lower than that of the parents in both the F1 and F2 generations. If individual mutations are only slightly deleterious, then they will tend to fixation at a high enough rate to cause lower hybrid fitness. If the fitness effects of mutation give rise to antagonistic epistasis, the hybrids tend to have a higher average fitness than the parental lines, suggesting a possible scenario for the origin of hybrid vigor. The other model of deleterious mutations investigated is the accumulation of knockout mutants in a duplicated gene family. While neutral in the parental lines, upon contact the F1 and later generations have a significant probability of carrying double knockouts. Under this scenario, selection may also favor reproductive isolation between the two lines. Even when the selection coefficients generated are too low to drive speciation, epistatic interactions between deleterious mutations offer a possible explanation for both outbreeding depression and hybrid vigor.     

The X chromosome and the rate of deleterious mutations in humans

Monosomy for the X chromosome in humans creates a genetic Achilles' heel for nature to deal with. We report that the human X chromosome appears to have one-third the density of the coding sequence of the autosomes and, because of partial shielding from the high mutation rate of the male sex, that it should also have a lower mutation rate than the autosomes (i.e.,.73). Hence, the X chromosome should contribute one quarter (.33x.73=.24) of the deleterious mutations expected from its DNA content. In this way, selection has possibly moderated risks from mutation in X-linked genes that are thought to have been fixed in their syntenic state since the onset of the mammalian lineage. The unexpected difference in the density of coding sequences indicates that our recent, hemophilia B-based estimate of the rate of deleterious mutations per zygote should be increased from 1.3 to 4 (1.3x3).     

The effect of nectar production on neighborhood size

Summary Bumblebee foraging behavior was observed on two plant species with similar floral and inflorescence structures. One species produces nectar while the other does not. Bees, upon visiting nectar producing flowers tend to empty them of nectar and by frequently moving between close neighbors, create a patchily distributed resource base. Bees maximize their foraging efficiency in such an environment by using an area-restricted searching behavior and flying distances inversely correlated with the quality of reward received. Pollen collecting bumblebees do not create a patchy environment and maximize their foraging efficiency by more consistently moving shorter distances. Pollen collecting bumblebees are significantly more likely to revisit flowers and to visit more flowers per inflorescence than are nectar gathering bumblebees. These differences in foraging behavior increase the neighborhood size for nectar producing species and make it increasingly unlikely that random drift will be a dominant mode of evolution in populations of these species.     

The effects of deleterious mutations on linked, neutral variation in small populations.

The effects of recessive, deleterious mutations on genetic variation at linked neutral loci can be heterozygosity-decreasing because of reduced effective population sizes or heterozygosity-increasing because of associative overdominance. Here we examine the balance between these effects by simulating individual diploid genotypes in small panmictic populations. The haploid genome consists of one linkage group with 1000 loci that can have deleterious mutations and a neutral marker. Combinations of the following parameters are studied: gametic mutation rate to harmful alleles (U), population size (N), recombination rate (r), selection coefficient (s), and dominance (h). Tight linkage (r 相似文献   

The effect of deleterious mutations and age on recombination in Drosophila melanogaster

At the population level, recombination mediates the efficiency with which selection can eliminate deleterious mutations. At the individual level, deleterious alleles may influence recombination, which would change the rate at which linkage disequilibrium is eroded and thereby alter the efficiency with which deleterious alleles are purged. Here, we test whether the presence of a deleterious allele on one autosome affects recombination on another autosome. We find that deleterious alleles not only alter the rate but also the pattern of recombination. However, there is little support that different deleterious alleles affect recombination in a consistent manner. Because we have detailed information on individual females across their lifetimes, we are able to examine how recombination patterns change with age and find that these patterns are also affected by the presence of deleterious alleles. The differences among genotypes or among age classes are large enough to add substantial noise to genetic mapping experiments that do not consider these sources of variation.     

Very slightly deleterious mutations and the molecular clock

Summary The model of very slightly deleterious mutations was examined from the standpoint of population genetics in relation to the molecular evolutionary clock. The distribution of selection coefficients of mutants (in terms of amino acid changes) with small effect is thought to be continuous around zero, with an average negative value. The variance of selection coefficients depends upon environmental diversity and hence on total population size of a species. By considering various examples of amino acid substitutions, the average and standard error of selection coefficients and the reciprocal of population size are assumed to have similar values. The model predicts negative correlation between evolutionary rate and population size. This effect is expected to be partially cancelled with the generation time effect of intrinsic mutation rate. Implications of this prediction on the molecular evolutionary clock are discussed.     

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.