Mitochondrial Mutation Rate, Spectrum and Heteroplasmy in Caenorhabditis elegans Spontaneous Mutation Accumulation Lines of Differing Population Size

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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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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Direct estimation of the spontaneous mutation rate by short-term mutation accumulation lines in Chironomus riparius

10.1101/086207 ◽

2016 ◽

Author(s):

Ann-Marie Oppold ◽

Markus Pfenninger

Keyword(s):

Mutation Rate ◽

De Novo ◽

Spontaneous Mutation ◽

Single Point ◽

Point Mutations ◽

Mutation Accumulation ◽

Occurrence Rate ◽

Spontaneous Mutation Rate ◽

Biting Midge ◽

Mutational Spectrum

AbstractMutations are the ultimate basis of evolution, yet their occurrence rate is known only for few species. We directly estimated the spontaneous mutation rate and the mutational spectrum in the non-biting midge C. riparius with a new approach. Individuals from ten mutation accumulation lines over five generations were deep genome sequenced to count de novo mutations (DNMs) that were not present in a pool of F1 individuals, representing parental genotypes. We identified 51 new single site mutations of which 25 were insertions or deletions and 26 single point mutations. This shift in the mutational spectrum compared to other organisms was explained by the high A/T content of the species. We estimated a haploid mutation rate of 2.1 x 10−9 (95% confidence interval: 1.4 x 10−9 – 3.1 x 10−9) which is in the range of recent estimates for other insects and supports the drift barrier hypothesis. We show that accurate mutation rate estimation from a high number of observed mutations is feasible with moderate effort even for non-model species.

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Low genetic variation is associated with low mutation rate in the giant duckweed

10.1101/381574 ◽

2018 ◽

Cited By ~ 1

Author(s):

Shuqing Xu ◽

Jessica Stapley ◽

Saskia Gablenz ◽

Justin Boyer ◽

Klaus J. Appenroth ◽

...

Keyword(s):

Genetic Diversity ◽

Population Size ◽

Mutation Rate ◽

Spontaneous Mutation ◽

Effective Population ◽

Spontaneous Mutation Rate ◽

Low Genetic Diversity ◽

Genome Wide ◽

Census Population Size

AbstractMutation rate and effective population size (Ne) jointly determine intraspecific genetic diversity, but the role of mutation rate is often ignored. We investigate genetic diversity, spontaneous mutation rate andNein the giant duckweed (Spirodela polyrhiza). Despite its large census population size, whole-genome sequencing of 68 globally sampled individuals revealed extremely low within-species genetic diversity. Assessed under natural conditions, the genome-wide spontaneous mutation rate is at least seven times lower than estimates made for other multicellular eukaryotes, whereasNeis large. These results demonstrate that low genetic diversity can be associated with large-Nespecies, where selection can reduce mutation rates to very low levels, and accurate estimates of mutation rate can help to explain seemingly counterintuitive patterns of genome-wide variation.One Sentence SummaryThe low-down on a tiny plant: extremely low genetic diversity in an aquatic plant is associated with its exceptionally low mutation rate.

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

10.1101/2021.07.12.452034 ◽

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.

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A broad mutational target explains an evolutionary trend

10.1101/2019.12.18.881250 ◽

2019 ◽

Author(s):

Fabrice Besnard ◽

Joao Picao-Osorio ◽

Clément Dubois ◽

Marie-Anne Félix

Keyword(s):

Cell Fate ◽

Mutation Rate ◽

Tandem Repeats ◽

Spontaneous Mutation ◽

Rapid Evolution ◽

Mutation Accumulation ◽

High Mutation Rate ◽

Genetic Linkage Analysis ◽

Evolutionary Trend ◽

Mutational Variance

ABSTRACTAn evolutionary trend, the rapid evolution of a trait in a group of organisms, can in some cases be explained by the mutational variance, the propensity of a phenotype to change under spontaneous mutation. However, the causes of high mutational variance are still elusive. For some morphological traits, fast evolution was shown to depend on the high mutation rate of one or few underlying loci with short tandem repeats. Here, we investigate the case of the fastest evolving cell fate among vulva precursor cells in Caenorhabditis nematodes, that of the cell called ‘P3.p’. For this, we combine mutation accumulation lines, whole-genome sequencing, genetic linkage analysis of the phenotype in recombinant lines, and candidate testing through mutant and CRISPR genome editing to identify causal mutations and the corresponding loci underlying the high mutational variance of P3.p. We identify and validate molecular lesions responsible for changes in this cell’s phenotype during a mutation accumulation experiment. We find that these loci do not present any characteristics of a high mutation rate, are scattered across the genome and belong to distinct biological pathways. Our data instead indicate that a broad mutational target size is the cause of the high mutational variance and of the corresponding evolutionary trend.

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Direct estimation of the spontaneous mutation rate by short-term mutation accumulation lines in Chironomus riparius

Evolution Letters ◽

10.1002/evl3.8 ◽

2017 ◽

Vol 1 (2) ◽

pp. 86-92 ◽

Cited By ~ 28

Author(s):

Ann-Marie Oppold ◽

Markus Pfenninger

Keyword(s):

Mutation Rate ◽

Spontaneous Mutation ◽

Mutation Accumulation ◽

Chironomus Riparius ◽

Short Term ◽

Spontaneous Mutation Rate ◽

Direct Estimation

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Global Gene Expression Divergence in Spontaneous Mutation Accumulation Lines of Caenorhabditis elegans under Varying Efficiency of Selection

10.1101/2021.05.03.442498 ◽

2021 ◽

Author(s):

Thaddeus C Deiss ◽

Anke Konrad ◽

Ulfar Bergthorsson ◽

Vaishali Katju

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Balancing Selection ◽

Spontaneous Mutation ◽

Global Gene Expression ◽

Mutation Accumulation ◽

Residual Variance ◽

Population Sizes ◽

Active Transcription ◽

Efficiency Of Selection

To ascertain the effect of relaxation of selection on global gene expression, Caenorhabditis elegans mutation accumulation (MA) lines were propagated under varying degrees of efficiency of selection determined by their different population sizes (N = 1, 10 and 100). Both the mutational variance (Vm), and the residual variance (Vr) were greatest in MA lines with the lowest efficiency of natural selection. The results suggest that gene expression is under strong balancing selection. Furthermore, mutations resulting in increased transcriptional noise or sensitivity to microenvironmental variation accumulate most under extreme genetic drift. In contrast, the Vm/Vr ratio was lowest in the N = 1 lines. Chromatin domains associated with broad gene silencing and active transcription exhibited the greatest and the smallest increase in transcriptional variation, respectively. Furthermore, the preponderance of overexpressed genes was especially pronounced in mitochondrial respiration, stress response, and immune system pathways, especially in low fitness N = 1 lines

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