scholarly journals Multigeneration Maximum-Likelihood Analysis Applied to Mutation-Accumulation Experiments in Caenorhabditis elegans

Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1193-1201 ◽  
Author(s):  
Peter D Keightley ◽  
Thomas M Bataillon
Keyword(s):  
Caenorhabditis Elegans ◽  
Maximum Likelihood ◽  
Method Of Moments ◽  
Mutation Accumulation ◽  
Life History Trait ◽  
Homozygous Mutation ◽  
C Elegans ◽  
Likelihood Analysis ◽  
Mean And Variance ◽  
Rule Out

AbstractWe develop a maximum-likelihood (ML) approach to estimate genomic mutation rates (U) and average homozygous mutation effects (s) from mutation-accumulation (MA) experiments in which phenotypic assays are carried out in several generations. We use simulations to compare the procedure's performance with the method of moments traditionally used to analyze MA data. Similar precision is obtained if mutation effects are small relative to the environmental standard deviation, but ML can give estimates of mutation parameters that have lower sampling variances than those obtained by the method of moments if mutations with large effects have accumulated. The inclusion of data from intermediate generations may improve the precision. We analyze life-history trait data from two Caenorhabditis elegans MA experiments. Under a model with equal mutation effects, the two experiments provide similar estimates for U of ~0.005 per haploid, averaged over traits. Estimates of s are more divergent and average at −0.51 and −0.13 in the two studies. Detailed analysis shows that changes of mean and variance of genetic values of MA lines in both C. elegans experiments are dominated by mutations with large effects, but the analysis does not rule out the presence of a large class of deleterious mutations with very small effects.

scholarly journals Natural variation in fecundity is correlated with species-wide levels of divergence in Caenorhabditis elegans

2021 ◽  
Author(s):  
Gaotian Zhang ◽  
Jake D Mostad ◽  
Erik C Andersen
Keyword(s):  
Life History ◽  
Caenorhabditis Elegans ◽  
Life History Traits ◽  
Life History Trait ◽  
Selective Sweeps ◽  
C Elegans ◽  
Genome Wide ◽  
Genetic Complexity ◽  
Genomic Regions ◽  
Global Population

Abstract Life history traits underlie the fitness of organisms and are under strong natural selection. A new mutation that positively impacts a life history trait will likely increase in frequency and become fixed in a population (e.g. a selective sweep). The identification of the beneficial alleles that underlie selective sweeps provides insights into the mechanisms that occurred during the evolution of a species. In the global population of Caenorhabditis elegans, we previously identified selective sweeps that have drastically reduced chromosomal-scale genetic diversity in the species. Here, we measured the fecundity of 121 wild C. elegans strains, including many recently isolated divergent strains from the Hawaiian islands and found that strains with larger swept genomic regions have significantly higher fecundity than strains without evidence of the recent selective sweeps. We used genome-wide association (GWA) mapping to identify three quantitative trait loci (QTL) underlying the fecundity variation. Additionally, we mapped previous fecundity data from wild C. elegans strains and C. elegans recombinant inbred advanced intercross lines that were grown in various conditions and detected eight QTL using GWA and linkage mappings. These QTL show the genetic complexity of fecundity across this species. Moreover, the haplotype structure in each GWA QTL region revealed correlations with recent selective sweeps in the C. elegans population. North American and European strains had significantly higher fecundity than most strains from Hawaii, a hypothesized origin of the C. elegans species, suggesting that beneficial alleles that caused increased fecundity could underlie the selective sweeps during the worldwide expansion of C. elegans.

scholarly journals Modified Moments and Maximum Likelihood Estimators for Parameters of Erlang Truncated Exponential Distribution

2021 ◽  
Vol 1 (1) ◽  
pp. 34-37
Author(s):  
Kannadasan Karuppaiah ◽  
Vinoth Raman
Keyword(s):  
Maximum Likelihood ◽  
Exponential Distribution ◽  
Method Of Moments ◽  
Scale Parameter ◽  
Likelihood Function ◽  
Continuous Distribution ◽  
Regression Estimators ◽  
Mean And Variance ◽  
Mathematical Derivation ◽  
Modified Moments

This study derives the parameter estimation in truncated form of a continuous distribution which is comparable to Erlang truncated exponential distribution. The shape and scale parameter will predict the whole distributions properties. Approximation will be useful in making the mathematical calculation an easy understand for non-mathematician or statistician. An explicit mathematical derivation is seen for some properties of, Method of Moments, Skewness, Kurtosis, Mean and Variance, Maximum Likelihood Function and Reliability Analysis. We compared ratio and regression estimators empirically based on bias and coefficient of variation.

scholarly journals Modified Moments and Maximum Likelihood Estimators for Parameters of Erlang Truncated Exponential Distribution

2021 ◽  
pp. 34-37
Author(s):  
Kannadasan Karuppaiah ◽  
◽  
Vinoth Raman ◽  
Keyword(s):  
Maximum Likelihood ◽  
Exponential Distribution ◽  
Method Of Moments ◽  
Scale Parameter ◽  
Likelihood Function ◽  
Continuous Distribution ◽  
Regression Estimators ◽  
Mean And Variance ◽  
Mathematical Derivation ◽  
Modified Moments

This study derives the parameter estimation in truncated form of a continuous distribution which is comparable to Erlang truncated exponential distribution. The shape and scale parameter will predict the whole distributions properties. Approximation will be useful in making the mathematical calculation an easy understand for non-mathematician or statistician. An explicit mathematical derivation is seen for some properties of, Method of Moments, Skewness, Kurtosis, Mean and Variance, Maximum Likelihood Function and Reliability Analysis. We compared ratio and regression estimators empirically based on bias and coefficient of variation.

Number of instars and sexual dimorphism of Tetropium fuscum (Coleoptera: Cerambycidae) larvae determined by maximum likelihood

2012 ◽  
Vol 144 (5) ◽  
pp. 720-726 ◽  
Author(s):  
Leah Flaherty ◽  
Jacques Régnière ◽  
Jon Sweeney
Keyword(s):  
Maximum Likelihood ◽  
Strong Support ◽  
Head Capsule ◽  
Sexually Dimorphic ◽  
Head Capsule Width ◽  
Likelihood Analysis ◽  
Mean And Variance ◽  
The Mean ◽  
Wood Borer ◽  
Tetropium Fuscum

AbstractTetropium fuscum (Fabricius) (Coleoptera: Cerambycidae) is a Palaearctic wood borer that has been established in Atlantic Canada since at least 1990. Neither the number of instars nor methods for determining the instar of field-collected larvae have been documented for this species. Head-capsule width was measured for 949 T. fuscum larvae in order to determine the number of instars in this species, estimate the mean and variance of head-capsule widths associated with each instar, and identify whether head-capsule width is sexually dimorphic. Head-capsule width data were analysed using maximum likelihood analysis of mixture models and the Brooks–Dyar rule. Our results provide strong support for the existence of six larval instars, with sexually dimorphic head-capsule widths in instars five and six. The probability of misclassifying larvae into instar-specific and sex-specific categories ranged from 0.6% to 12.8%, with the highest probabilities occurring when assigning a sex to fifth-instar and sixth-instar larvae.

scholarly journals Mutation rate and spectrum in Caenorhabditis elegans mutation accumulation lines subjected to RNAi-induced knockdown of the mismatch repair gene msh-2

2021 ◽  
Author(s):  
Vaishali Katju ◽  
Anke Konrad ◽  
Thaddeus C. Deiss ◽  
Ulfar Bergthorsson
Keyword(s):  
Caenorhabditis Elegans ◽  
Mismatch Repair ◽  
Mutation Rate ◽  
Copy Number ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Mutational Bias ◽  
C Elegans ◽  
Small Indels ◽  
Local Sequence

DNA mismatch repair (MMR), an evolutionarily conserved repair pathway shared by prokaryotic and eukaryotic species alike, influences molecular evolution by detecting and correcting mismatches that escape DNA polymerase proofreading, thereby protecting genetic fidelity, reducing the mutational load, and preventing lethality. Herein we conduct the first genome-wide evaluation of the alterations to the mutation rate and spectrum under impaired activity of the MutS homolog, msh-2, in Caenorhabditis elegans. We performed mutation accumulation (MA) under RNAi-induced knockdown of msh-2 for 50 generations in obligately outcrossing fog-2(lf) lines, followed by next-generation sequencing of 19 MA lines and the ancestral control. msh-2 impairment substantially increased the frequency of nuclear base substitutions (~23x) and small indels (~328x) relative to wildtype. However, we observed no increase in the mutation rates of mtDNA, and copy-number changes of single-copy genes. There was a marked increase in copy-number variation of rDNA genes under MMR impairment. In C. elegans, msh-2 repairs transitions more efficiently than transversions as well as increases the AT mutational bias relative to wildtype. The local sequence context, including sequence complexity, G+C-content, and flanking bases influenced the mutation rate. The X chromosome had a lower substitution and higher indel rate than autosomes, which can either result from sex-specific mutation rates or a nonrandom distribution of mutable sites in the genome. Comparison of MMR impairment in C. elegans to that in other species shows that the specificity of the MMR varies between taxa, and is more efficient in detecting and repairing small indels in eukaryotes relative to prokaryotes.

scholarly journals Analysis of mutation accumulation experiments: response to Deng, Li and Li

1999 ◽  
Vol 74 (1) ◽  
pp. 87-91 ◽  
Author(s):  
PETER D. KEIGHTLEY
Keyword(s):  
Monte Carlo ◽  
Maximum Likelihood ◽  
Monte Carlo Simulations ◽  
Method Of Moments ◽  
Critical Points ◽  
Considerable Increase ◽  
Mutation Accumulation ◽  
Using Data

A recent paper in this journal by Deng, Li and Li has investigated methods to estimate rates and effects of polygenic mutations using data from mutation accumulation experiments. Here, I evaluate a number of critical points in this paper concerning a maximum likelihood (ML) procedure to analyse mutation accumulation data. I show that Deng, Li and Li's criticisms are based on misunderstandings, or numerical problems they encountered that could have been readily overcome. In Monte Carlo simulations, I show that ML can give a considerable increase in precision over the method of moments that is traditionally used to analyse mutation accumulation data. Furthermore, ML allows the comparison of the fit of different models for the distribution of mutation effects.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

The Effect of Mianserin on Lifespan of Caenorhabditis elegans is Abolished by Glucose

2021 ◽  
Vol 13 ◽  
Author(s):  
Abdullah Almotayri ◽  
Jency Thomas ◽  
Mihiri Munasinghe ◽  
Markandeya Jois
Keyword(s):  
Caenorhabditis Elegans ◽  
Scaffolding Protein ◽  
Lifespan Extension ◽  
Wild Type ◽  
E Coli ◽  
C Elegans ◽  
Risk Of Death ◽  
Increased Risk ◽  
Antidepressant Use ◽  
Extension Effect

Background: The antidepressant mianserin has been shown to extend the lifespan of Caenorhabditis elegans (C. elegans), a well-established model organism used in aging research. The extension of lifespan in C. elegans was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegans in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin. Objective: To investigate the effect of glucose added to the diet of C. elegans on the lifespan-extension effect of mianserin. Methods: Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test. Results: Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin. Conclusion: The addition of glucose to the diet of C. elegans abolishes the lifespan-extension effects of mianserin.

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