Mutation Accumulation in Real Branches: Fitness Assays for Genomic Deleterious Mutation Rate and Effect in Large‐Statured Plants

Repeated efforts to estimate the genomic deleterious mutation rate per generation (U) in Drosophila melanogaster have yielded inconsistent estimates ranging from 0·01 to nearly 1. We carried out a mutation-accumulation experiment with a cryopreserved control population in hopes of resolving some of the uncertainties raised by these estimates. Mutation accumulation (MA) was carried out by brother–sister mating of 150 sublines derived from two inbred lines. Fitness was measured under conditions chosen to mimic the ancestral laboratory environment of these genotypes. We monitored the insertions of a transposable element, copia, that proved to accumulate at the unusually high rate of 0·24 per genome per generation in one of our MA lines. Mutational variance in fitness increased at a rate consistent with previous studies, yielding a mutational coefficient of variation greater than 3%. The performance of the cryopreserved control relative to the MA lines was inconsistent, so estimates of mutation rate by the Bateman–Mukai method are suspect. Taken at face value, these data suggest a modest decline in fitness of about 0·3% per generation. The element number of copia was a significant predictor of fitness within generations; on average, insertions caused a 0·76% loss in fitness, although the confidence limits on this estimate are wide.

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The Effect of Overdominance on Characterizing Deleterious Mutations in Large Natural Populations

Genetics ◽

10.1093/genetics/151.2.895 ◽

1999 ◽

Vol 151 (2) ◽

pp. 895-913 ◽

Cited By ~ 2

Author(s):

Jin-Long Li ◽

Jian Li ◽

Hong-Wen Deng

Keyword(s):

Genetic Variation ◽

Mutation Rate ◽

Deleterious Mutation ◽

Natural Populations ◽

Mutation Accumulation ◽

Statistical Properties ◽

Alternative Methods ◽

Deleterious Mutations ◽

Selection Coefficient ◽

New Approaches

Abstract Alternatives to the mutation-accumulation approach have been developed to characterize deleterious genomic mutations. However, they all depend on the assumption that the standing genetic variation in natural populations is solely due to mutation-selection (M-S) balance and therefore that overdominance does not contribute to heterosis. Despite tremendous efforts, the extent to which this assumption is valid is unknown. With different degrees of violation of the M-S balance assumption in large equilibrium populations, we investigated the statistical properties and the robustness of these alternative methods in the presence of overdominance. We found that for dominant mutations, estimates for U (genomic mutation rate) will be biased upward and those for h̄ (mean dominance coefficient) and s̄ (mean selection coefficient), biased downward when additional overdominant mutations are present. However, the degree of bias is generally moderate and depends largely on the magnitude of the contribution of overdominant mutations to heterosis or genetic variation. This renders the estimates of U and s̄ not always biased under variable mutation effects that, when working alone, cause U and s̄ to be underestimated. The contributions to heterosis and genetic variation from overdominant mutations are monotonic but not linearly proportional to each other. Our results not only provide a basis for the correct inference of deleterious mutation parameters from natural populations, but also alleviate the biggest concern in applying the new approaches, thus paving the way for reliably estimating properties of deleterious mutations.

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Comparing Analysis Methods for Mutation-Accumulation Data: A Simulation Study

Genetics ◽

10.1093/genetics/164.2.807 ◽

2003 ◽

Vol 164 (2) ◽

pp. 807-819 ◽

Cited By ~ 4

Author(s):

Aurora García-Dorado ◽

Araceli Gallego

Keyword(s):

Mutation Rate ◽

Gamma Distribution ◽

Deleterious Mutation ◽

Empirical Distribution ◽

Mutation Accumulation ◽

High Rate ◽

Good Precision ◽

Appreciable Increase ◽

Fitness Trait ◽

The Mean

Abstract We simulated single-generation data for a fitness trait in mutation-accumulation (MA) experiments, and we compared three methods of analysis. Bateman-Mukai (BM) and maximum likelihood (ML) need information on both the MA lines and control lines, while minimum distance (MD) can be applied with or without the control. Both MD and ML assume gamma-distributed mutational effects. ML estimates of the rate of deleterious mutation had larger mean square error (MSE) than MD or BM had due to large outliers. MD estimates obtained by ignoring the mean decline observed from comparison to a control are often better than those obtained using that information. When effects are simulated using the gamma distribution, reducing the precision with which the trait is assayed increases the probability of obtaining no ML or MD estimates but causes no appreciable increase of the MSE. When the residual errors for the means of the simulated lines are sampled from the empirical distribution in a MA experiment, instead of from a normal one, the MSEs of BM, ML, and MD are practically unaffected. When the simulated gamma distribution accounts for a high rate of mild deleterious mutation, BM detects only ∼30% of the true deleterious mutation rate, while MD or ML detects substantially larger fractions. To test the robustness of the methods, we also added a high rate of common contaminant mutations with constant mild deleterious effect to a low rate of mutations with gamma-distributed deleterious effects and moderate average. In that case, BM detects roughly the same fraction as before, regardless of the precision of the assay, while ML fails to provide estimates. However, MD estimates are obtained by ignoring the control information, detecting ∼70% of the total mutation rate when the mean of the lines is assayed with good precision, but only 15% for low-precision assays. Contaminant mutations with only tiny deleterious effects could not be detected with acceptable accuracy by any of the above methods.

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On the Rate and Linearity of Viability Declines in Drosophila Mutation-Accumulation Experiments: Genomic Mutation Rates and Synergistic Epistasis Revisited

Genetics ◽

10.1093/genetics/166.2.797 ◽

2004 ◽

Vol 166 (2) ◽

pp. 797-806 ◽

Cited By ~ 4

Author(s):

James D Fry

Keyword(s):

Mutation Rate ◽

Average Rate ◽

Natural Populations ◽

Mutation Accumulation ◽

High Rate ◽

Deleterious Mutations ◽

Order Of Magnitude ◽

Contamination Event ◽

Genomic Mutation ◽

The 1960S

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

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Nature of Deleterious Mutation Load in Drosophila

Genetics ◽

10.1093/genetics/144.4.1993 ◽

1996 ◽

Vol 144 (4) ◽

pp. 1993-1999 ◽

Cited By ~ 5

Author(s):

Peter D Keightley

Keyword(s):

Deleterious Mutation ◽

Spontaneous Mutation ◽

Mutation Accumulation ◽

Mutation Rates ◽

Mutation Load ◽

Spontaneous Mutation Rate ◽

A Minor ◽

Chromosome I ◽

Balancer Chromosomes ◽

Balancer Chromosome

Much population genetics and evolution theory depends on knowledge of genomic mutation rates and distributions of mutation effects for fitness, but most information comes from a few mutation accumulation experiments in Drosophila in which replicated chromosomes are sheltered from natural selection by a balancer chromosome. I show here that data from these experiments imply the existence of a large class of minor viability mutations with approximately equivalent effects. However, analysis of the distribution of viabilities of chromosomes exposed to EMS mutagenesis reveals a qualitatively different distribution of effects lacking such a minor effects class. A possible explanation for this difference is that transposable element insertions, a common class of spontaneous mutation event in Drosophila, frequently generate minor viability effects. This explanation would imply that current estimates of deleterious mutation rates are not generally applicable in evolutionary models, as transposition rates vary widely. Alternatively, much of the apparent decline in viability under spontaneous mutation accumulation could have been nonmutational, perhaps due to selective improvement of balancer chromosomes. This explanation accords well with the data and implies a spontaneous mutation rate for viability two orders of magnitude lower than previously assumed, with most mutation load attributable to major effects.

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The Rate of Spontaneous Mutation for Life-History Traits in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/151.1.119 ◽

1999 ◽

Vol 151 (1) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Larissa L Vassilieva ◽

Michael Lynch

Keyword(s):

Life History ◽

Caenorhabditis Elegans ◽

Mutation Rate ◽

Life History Traits ◽

Deleterious Mutation ◽

Spontaneous Mutation ◽

Spontaneous Mutations ◽

Homozygous State ◽

Mutational Effect ◽

Biological Differences

Abstract Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of ∼50 generations. Periodic assays of these lines and comparison to a frozen control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability ∼0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.

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Spontaneous rate of clonal mutations in Daphnia galeata

10.1101/2020.08.31.275495 ◽

2020 ◽

Author(s):

Markus Pfenninger ◽

Halina Binde Doria ◽

Jana Nickel ◽

Anne Thielsch ◽

Klaus Schwenk ◽

...

Keyword(s):

Mutation Rate ◽

De Novo ◽

Mutation Accumulation ◽

Parental Genotype ◽

De Novo Mutations ◽

Daphnia Galeata ◽

Short Term ◽

Heritable Variation ◽

Nucleotide Mutation ◽

Ultimate Source

AbstractMutations are the ultimate source of heritable variation and therefore the fuel for evolution, but direct estimates exist only for few species. We estimated the spontaneous nucleotide mutation rate among clonal generations in the waterflea Daphnia galeata with a short term mutation accumulation approach. Individuals from eighteen mutation accumulation lines over five generations were deep genome sequenced to count de novo mutations that were not present in a pool of F1 individuals, representing the parental genotype. We identified 12 new nucleotide mutations in 90 clonal generational passages. This resulted in an estimated haploid mutation rate of 0.745 x 10-9 (95% c.f. 0.39 x 10-9 − 1.26 x 10-9), which is slightly lower than recent estimates for other Daphnia species. We discuss the implications for the population genetics of Cladocerans.

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Deleterious mutation accumulation and the regeneration of genetic resources

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.95.1.394 ◽

1998 ◽

Vol 95 (1) ◽

pp. 394-399 ◽

Cited By ~ 39

Author(s):

D. J. Schoen ◽

J. L. David ◽

T. M. Bataillon

Keyword(s):

Genetic Resources ◽

Deleterious Mutation ◽

Mutation Accumulation

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First Estimation of the Spontaneous Mutation Rate in Diatoms

Genome Biology and Evolution ◽

10.1093/gbe/evz130 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1829-1837 ◽

Cited By ~ 11

Author(s):

Marc Krasovec ◽

Sophie Sanchez-Brosseau ◽

Gwenael Piganeau

Keyword(s):

Mutation Rate ◽

Spontaneous Mutation ◽

Mutation Accumulation ◽

Mutation Rates ◽

Model Organisms ◽

Base Substitution ◽

Unicellular Eukaryote ◽

Fundamental Parameter ◽

Secondary Endosymbiosis ◽

Spontaneous Mutation Rate

Abstract Mutations are the origin of genetic diversity, and the mutation rate is a fundamental parameter to understand all aspects of molecular evolution. The combination of mutation–accumulation experiments and high-throughput sequencing enabled the estimation of mutation rates in most model organisms, but several major eukaryotic lineages remain unexplored. Here, we report the first estimation of the spontaneous mutation rate in a model unicellular eukaryote from the Stramenopile kingdom, the diatom Phaeodactylum tricornutum (strain RCC2967). We sequenced 36 mutation accumulation lines for an average of 181 generations per line and identified 156 de novo mutations. The base substitution mutation rate per site per generation is μbs = 4.77 × 10−10 and the insertion–deletion mutation rate is μid = 1.58 × 10−11. The mutation rate varies as a function of the nucleotide context and is biased toward an excess of mutations from GC to AT, consistent with previous observations in other species. Interestingly, the mutation rates between the genomes of organelles and the nucleus differ, with a significantly higher mutation rate in the mitochondria. This confirms previous claims based on indirect estimations of the mutation rate in mitochondria of photosynthetic eukaryotes that acquired their plastid through a secondary endosymbiosis. This novel estimate enables us to infer the effective population size of P. tricornutum to be Ne∼8.72 × 106.

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EFFECT OF DELETERIOUS MUTATION-ACCUMULATION ON THE FITNESS OF RNA BACTERIOPHAGE MS2

Evolution ◽

10.1111/j.0014-3820.2000.tb00069.x ◽

2000 ◽

Vol 54 (2) ◽

pp. 686-691 ◽

Cited By ~ 11

Author(s):

Marcos Penta ◽

Santiago F. Elena ◽

Andres Moya

Keyword(s):

Deleterious Mutation ◽

Mutation Accumulation ◽

Bacteriophage Ms2

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