scholarly journals Spontaneous mutation rate of modifiers of metabolism in Drosophila.

Genetics ◽  
1995 ◽  
Vol 139 (2) ◽  
pp. 767-779 ◽  
Author(s):  
A G Clark ◽  
L Wang ◽  
T Hulleberg
Keyword(s):  
Spontaneous Mutation ◽  
Balance Model ◽  
Environmental Variance ◽  
Spontaneous Mutation Rate ◽  
Empirical Estimates ◽  
Quantitative Genetic ◽  
Rate Of Increase ◽  
Rigorous Test ◽  
Quantitative Genetic Parameters ◽  
New Mutations

Abstract A rigorous test of our understanding of evolutionary quantitative genetics would be to predict accurately the equilibrium distribution of a character from empirical estimates of the relevant parameters in a mutation-selection-drift balance model. An aspect of this problem that is amenable to experimental analysis is the distribution of the effects of new mutations. This study quantifies the divergence among 200 lines of Drosophila melanogaster as they accumulated mutations on the second chromosome and estimates the rate of increase of variation and covariation in metabolic characters. Amounts of stored triacylglycerol and glycogen and the activities of a series of 12 metabolic enzymes were assayed in a subset of lines at generations 0, 11, 22, 33 and 44. Analyses of the rate of increase in the among-line variance in each trait allowed estimation of Vm/Ve, the ratio of among-line variance added per generation to the environmental variance. Values of Vm/Ve for the second chromosome ranged from 0.0004 to 0.0289 per generation. Six of the 16 characters showed significant departure from a normal distribution, and several lines exhibited large changes in more than one character. The covariance of pairs of traits also was partitioned into a within-line component (environmental covariance, Cov(e)) and an among-line component (mutational covariance, Covm). Both variances and covariance among lines increased over time, as assessed by linear regression, whereas environmental covariance showed no such trend. Results indicate that the quantitative genetic parameters describing the variation in metabolic traits are similar to those of other continuous characters.

scholarly journals Spontaneous mutations and the origin and maintenance of quantitative genetic variation

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wen Huang ◽  
Richard F Lyman ◽  
Rachel A Lyman ◽  
Mary Anna Carbone ◽  
Susan T Harbison ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Quantitative Traits ◽  
Spontaneous Mutation ◽  
Natural Populations ◽  
Empirical Work ◽  
Stabilizing Selection ◽  
Spontaneous Mutation Rate ◽  
Evolutionary Forces ◽  
Quantitative Genetic

Mutation and natural selection shape the genetic variation in natural populations. Here, we directly estimated the spontaneous mutation rate by sequencing new Drosophila mutation accumulation lines maintained with minimal natural selection. We inferred strong stabilizing natural selection on quantitative traits because genetic variation among wild-derived inbred lines was much lower than predicted from a neutral model and the mutational effects were much larger than allelic effects of standing polymorphisms. Stabilizing selection could act directly on the traits, or indirectly from pleiotropic effects on fitness. However, our data are not consistent with simple models of mutation-stabilizing selection balance; therefore, further empirical work is needed to assess the balance of evolutionary forces responsible for quantitative genetic variation.

A Mutation in a Saccharomyces cerevisiae Gene (RAD3) Required for Nucleotide Excision Repair and Transcription Increases the Efficiency of Mismatch Correction

Genetics ◽  
1996 ◽  
Vol 144 (2) ◽  
pp. 459-466 ◽  
Author(s):  
Yingying Yang ◽  
Anthony L Johnson ◽  
Leland H Johnston ◽  
Wolfram Siede ◽  
Errol C Friedberg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mismatch Repair ◽  
Excision Repair ◽  
Spontaneous Mutation ◽  
Surprising Result ◽  
Spontaneous Mutation Rate ◽  
Mismatch Correction ◽  
Nucleotide Excision ◽  
Repair Genes ◽  
Type Strains

Abstract RAD3 functions in DNA repair and transcription in Saccharomyces cerevisiae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the potential involvement of the Rad3 protein in mismatch correction by comparing heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutation rate but did not prevent heteroduplex repair or bias its directionality. Instead, the efficiency of mismatch correction was enhanced in the rad3-1 strain. This surprising result prompted us to examine expression of yeast mismatch repair genes. We determined that MSH2, but not MLH1, is transcriptionally regulated during the cell-cycle like PMSl, and that rad3-1 does not increase the transcript levels for these genes in log phase cells. These observations suggest that the rad3-1 mutation gives rise to an enhanced efficiency of mismatch correction via a process that does not involve transcriptional regulation of mismatch repair. Interestingly, mismatch repair also was more efficient when error-editing by yeast DNA polymerase δ was eliminated. We discuss our results in relation to possible mechanisms that may link the rad3-1 mutation to mismatch correction efficiency.

scholarly journals Nature of Deleterious Mutation Load in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1993-1999 ◽  
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.

Gonad Temperature and Spontaneous Mutation-rate in Man

Nature ◽  
1957 ◽  
Vol 180 (4599) ◽  
pp. 1433-1434 ◽  
Author(s):  
LARS EHEENBERG ◽  
GÜNTER VON EHRENSTEIN ◽  
ARNE HEDGRAN
Keyword(s):  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Spontaneous Mutation Rate

scholarly journals Phenotypic plasticity of labile traits in the wild

2013 ◽  
Vol 59 (4) ◽  
pp. 485-505 ◽  
Author(s):  
Jon E. Brommer
Keyword(s):  
Life History ◽  
Phenotypic Plasticity ◽  
Statistical Approach ◽  
Scale Up ◽  
Population Level ◽  
Wild Populations ◽  
Quantitative Genetic ◽  
In The Wild ◽  
The Individual ◽  
Quantitative Genetic Parameters

Abstract Individual-based studies allow quantification of phenotypic plasticity in behavioural, life-history and other labile traits. The study of phenotypic plasticity in the wild can shed new light on the ultimate objectives (1) whether plasticity itself can evolve or is constrained by its genetic architecture, and (2) whether plasticity is associated to other traits, including fitness (selection). I describe the main statistical approach for how repeated records of individuals and a description of the environment (E) allow quantification of variation in plasticity across individuals (IxE) and genotypes (GxE) in wild populations. Based on a literature review of life-history and behavioural studies on plasticity in the wild, I discuss the present state of the two objectives listed above. Few studies have quantified GxE of labile traits in wild populations, and it is likely that power to detect statistically significant GxE is lacking. Apart from the issue of whether it is heritable, plasticity tends to correlate with average trait expression (not fully supported by the few genetic estimates available) and may thus be evolutionary constrained in this way. Individual-specific estimates of plasticity tend to be related to other traits of the individual (including fitness), but these analyses may be anti-conservative because they predominantly concern stats-on-stats. Despite the increased interest in plasticity in wild populations, the putative lack of power to detect GxE in such populations hinders achieving general insights. I discuss possible steps to invigorate the field by moving away from simply testing for presence of GxE to analyses that ‘scale up’ to population level processes and by the development of new behavioural theory to identify quantitative genetic parameters which can be estimated.

Scope of action of the immunoglobulin mutator system

Genome ◽  
1989 ◽  
Vol 31 (1) ◽  
pp. 118-121 ◽  
Author(s):  
Matthias R. Wabl ◽  
Hans-Martin Jäck ◽  
R. C. von Borstel ◽  
Charles M. Steinberg
Keyword(s):  
B Cell ◽  
Mutation Rate ◽  
Heavy Chain ◽  
B Lymphocyte ◽  
Somatic Hypermutation ◽  
Spontaneous Mutation ◽  
Cell Lineage ◽  
Variable Region ◽  
High Rate ◽  
Spontaneous Mutation Rate

The authors have developed a method to measure the rate of spontaneous mutations taking place in IgH, the gene encoding the immunoglobulin heavy chain. When an amber chain-termination codon mutates to a sense codon, translation of the polypeptide chain will be completed, and mutant cells producing the heavy chain can be detected with a fluorescent labelled antibody. The protocol used is the compartmentalization test which minimizes any effect of selection. In subclones of the pre-B lymphocyte line 18–81, the spontaneous mutation rate in the part of IgH encoding the variable region is somewhat greater than 10−5 mutations per base pair per generation. This supports the hypothesis that hypermutation is not dependent on cell stimulation by an antigen. In a hybrid between a cell of this line and a myeloma (which represents the terminal stage of the B-cell lineage), the mutation rate was too low to be determined by this test, less than 10−9. When the same loss to gain procedure system was used with an opal chain-terminating codon in the part of IgH encoding the constant region (Cμ), a high rate of reversion by deletion was found. Long (more than one exon) and short (less than one exon) deletions occurred at rates of 1.7 × 10−5 and 1.4 × 10−7 per generation, respectively. It is thought that the high rate of deletion is not related to somatic hypermutation but rather to DNA rearrangement during the heavy-chain class switch, which is occurring in these pre-B cell lines. The point mutation rate was too low to be detected above the background of deletion mutants, less than 5 × 10−8. The immunoglobulin mutator system works weakly, if at all, on two other, nonimmunoglobulin, genes tested: B2m (β2 microglobulin) and the gene for ouabain resistance.Key words: pre-B lymphocyte, B lymphocyte, spontaneous mutation rate, compartmentalization test, deletion mutation, hypermutation.

scholarly journals Mutation avoidance and DNA repair proficiency in Ustilago maydis are differentially lost with progressive truncation of the REC1 gene product.

1995 ◽  
Vol 15 (10) ◽  
pp. 5329-5338 ◽  
Author(s):  
K Onel ◽  
M P Thelen ◽  
D O Ferguson ◽  
R L Bennett ◽  
W K Holloman
Keyword(s):  
Amino Acid ◽  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Ustilago Maydis ◽  
Radiation Sensitivity ◽  
Open Reading Frame ◽  
Exonuclease Activity ◽  
Amino Acid Residues ◽  
Spontaneous Mutation Rate ◽  
Reading Frame

The REC1 gene of Ustilago maydis has an uninterrupted open reading frame, predicted from the genomic sequence to encode a protein of 522 amino acid residues. Nevertheless, an intron is present, and functional activity of the gene in mitotic cells requires an RNA processing event to remove the intron. This results in a change in reading frame and production of a protein of 463 amino acid residues. The 3'-->5' exonuclease activity of proteins derived from the REC1 genomic open reading frame, the intronless open reading frame, and several mutants was investigated. The mutants included a series of deletions constructed by removing restriction fragments at the 3' end of the cloned REC1 gene and a set of mutant alleles previously isolated in screens for radiation sensitivity. All of these proteins were overproduced in Escherichia coli as N-terminal polyhistidine-tagged fusions that were subsequently purified by immobilized metal affinity chromatography and assayed for 3'-->5' exonuclease activity. The results indicated that elimination of the C-terminal third of the protein did not result in a serious reduction in 3'-->5' exonuclease activity, but deletion into the midsection caused a severe loss of activity. The biological activity of the rec1-1 allele, which encodes a truncated polypeptide with full 3'-->5' exonuclease activity, and the rec1-5 allele, which encodes a more severely truncated polypeptide with no exonuclease activity, was investigated. The two mutants were equally sensitive to the lethal effect of UV light, but the spontaneous mutation rate was elevated 10-fold over the wild-type rate in the rec1-1 mutant and 100-fold in the rec1-5 mutant. The elevated spontaneous mutation rate correlated with the ablation of exonuclease activity, but the radiation sensitivity did not. These results indicate that the C-terminal portion of the Rec1 protein is not essential for exonuclease activity but is crucial in the role of REC1 in DNA damage repair.

scholarly journals First Estimation of the Spontaneous Mutation Rate in Diatoms

2019 ◽  
Vol 11 (7) ◽  
pp. 1829-1837 ◽  
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.

scholarly journals Evidence Concerning the Inadequacy of Mutation as an Explanation of the Frequency of the Sickle Cell Gene in the Belgian Congo

Blood ◽  
1955 ◽  
Vol 10 (4) ◽  
pp. 341-350 ◽  
Author(s):  
J. M. VANDEPITTE ◽  
WOLF W. ZUELZER ◽  
JAMES V. NEEL ◽  
J. COLAERT
Keyword(s):  
Natural Selection ◽  
Sickle Cell ◽  
Spontaneous Mutation ◽  
Genetic Modifier ◽  
Paper Electrophoresis ◽  
Preliminary Calculation ◽  
Spontaneous Mutation Rate ◽  
Balanced Polymorphism ◽  
Belgian Congo ◽  
Cell Gene

Abstract It is pointed out that there are two outstanding (and not mutually exclusive) possible explanations for the persistence of the sickle cell gene in the face of strong negative natural selection. These are (1) "balanced polymorphism," and (2) a high spontaneous mutation rate. In Léopoldville, Belgian Congo, approximately 25 per cent of the natives exhibit the sickling phenomenon. Over a two and one-half year period 261 patients with sickle cell disease, distributed among 243 families, were seen at the Institute of Tropical Medicine in Léopoldville. A total of 233 of the 243 mothers of the patients in this series was tested for the sickling phenomenon. Only two failed to sickle. Hemoglobin from these two women was normal on paper electrophoresis. The occurrence of these two exceptional mothers can be explained on the basis of mutation at some stage of oogenesis resulting in a sickle cell gene. Alternate possible explanations include (1) transmission by the mother of some other abnormal gene affecting hemoglobin synthesis, (2) occurrence in the mother of a genetic modifier of the effects of the sickle cell gene, (or its normal allele), and (3) unreported adoption. These data make possible a preliminary calculation of the extent to which mutation may be responsible for maintaining the sickle cell gene. Calculations based on the assumption that both these exceptional mothers indicate the occurrence of a mutation will lead to maximal estimates of the rate of mutation of the sickle cell gene. This maximal estimate is 1.7 x 10-3 per gene per generation. This rate, although very high by the usual standards of human mutation rates, is only approximately one-tenth that necessary to offset natural selection in a population with 25 per cent sickling.

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