scholarly journals A broad mutational target explains an evolutionary trend

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.

scholarly journals A broad mutational target explains a fast rate of phenotypic evolution

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Fabrice Besnard ◽  
Joao Picao-Osorio ◽  
Clément Dubois ◽  
Marie-Anne Félix
Keyword(s):  
Cell Fate ◽  
Mutation Rate ◽  
Tandem Repeats ◽  
Spontaneous Mutation ◽  
Rapid Evolution ◽  
High Mutation Rate ◽  
Sustained Action ◽  
Fast Evolution ◽  
Mutational Variance ◽  
Short Tandem

The rapid evolution of a trait in a clade of organisms can be explained by the sustained action of natural selection or by a high mutational variance, that is the propensity to change under spontaneous mutation. The causes for a high mutational variance are still elusive. In some cases, fast evolution depends on the high mutation rate of one or few loci with short tandem repeats. Here, we report on the fastest evolving cell fate among vulva precursor cells in Caenorhabditis nematodes, that of P3.p. We identify and validate causal mutations underlying P3.p's high mutational variance. We find that these positions do not present any characteristics of a high mutation rate, are scattered across the genome and the corresponding genes belong to distinct biological pathways. Our data indicate that a broad mutational target size is the cause of the high mutational variance and of the corresponding fast phenotypic evolutionary rate.

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

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.

scholarly journals Mutation accumulation and the effect of copia insertions in Drosophila melanogaster

2004 ◽  
Vol 83 (1) ◽  
pp. 7-18 ◽  
Author(s):  
DAVID HOULE ◽  
SERGEY V. NUZHDIN
Keyword(s):  
Drosophila Melanogaster ◽  
Mutation Rate ◽  
Deleterious Mutation ◽  
Mutation Accumulation ◽  
Inbred Lines ◽  
High Rate ◽  
Confidence Limits ◽  
Laboratory Environment ◽  
Element Number ◽  
Mutational Variance

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.

scholarly journals A larger target leads to faster evolution

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Bing Yang ◽  
Scott A Rifkin
Keyword(s):  
Cell Fate ◽  
Mutation Rate ◽  
High Mutation Rate ◽  
Cell Fate Decision ◽  
Number Of Genes ◽  
A Cell ◽  
Fate Decision

The speed at which a cell fate decision in nematode worms evolves is due to the number of genes that control the decision, rather than to a high mutation rate.

scholarly journals The mutation rates and mutational bias of influenza A virus

2017 ◽  
Author(s):  
Matthew D. Pauly ◽  
Megan Procario ◽  
Adam S. Lauring
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Mutation Rate ◽  
Influenza A ◽  
Rapid Evolution ◽  
Viral Fitness ◽  
High Mutation Rate ◽  
Mutation Rates ◽  
Mutational Bias ◽  
Neutral Mutations

AbstractInfluenza virus has a high mutation rate, and this low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the mutation rate of influenza A virus is 7.1 × 10−6− 4.5 × 10−5substitutions per nucleotide per cell infection cycle and 2.7 × 10−6− 3.0 × 10−5substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal impacts on viral fitness and fluctuation tests typically investigate only a subset of the twelve mutational classes. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins. This method allowed us to measure the rates of selectively neutral mutations representative of all 12 mutational classes in the context of an unstructured RNA. We measured an overall mutation rate of 1.8 × 10−4s/n/r for PR8 (H1N1) and 2.5 × 10−4s/n/r for Hong Kong 2014 (H3N2). The replication mode was linear. The mutation rates of these divergent strains are significantly higher than previous estimates and suggest that each replicated genome will have an average of 2-3 mutations. The viral mutational spectrum is heavily biased toward A to G and U to C transitions, resulting in a transition to transversion bias of 2.7 and 3.6 for the two strains. These mutation rates were relatively constant over a range of physiological temperatures. Our high-resolution analysis of influenza virus mutation rates will enable more refined models of its molecular evolution.SignificanceThe rapid evolution of influenza virus is a major problem in public health. A key factor driving this rapid evolution is the virus’ very high mutation rate. We developed a new method for measuring the rates of all 12 mutational classes in influenza virus, which eliminates some of the biases of existing assays. We find that the influenza virus mutation rate is much higher than previously reported and is consistent across two distinct strains and a range of temperatures. Our data suggest that influenza viruses replicate at their maximally tolerable mutation rates, highlighting both the virus’ evolutionary potential and its significant constraints.

scholarly journals The variable ELF3 polyglutamine tract mediates complex epistatic interactions in Arabidopsis thaliana

2016 ◽  
Author(s):  
◽  
Christine Queitsch
Keyword(s):  
Arabidopsis Thaliana ◽  
Genetic Variation ◽  
Mutation Rate ◽  
Short Tandem Repeats ◽  
Tandem Repeats ◽  
High Mutation Rate ◽  
Hybrid Strategy ◽  
Coding Regions ◽  
Polyglutamine Tract ◽  
Short Tandem

ABSTRACTShort tandem repeats are hypervariable genetic elements that occur frequently in coding regions. Their high mutation rate readily generates genetic variation contributing to adaptive evolution and human diseases. We recently proposed that short tandem repeats are likely to engage in epistasis because they are well-positioned to compensate for genetic variation arising at other loci due to their high mutation rate. We previously reported that natural ELF3 polyglutamine variants cause reciprocal genetic incompatibilities in two divergent Arabidopsis thaliana backgrounds. Here, we dissected the genetic architecture of this incompatibility and used a yeast two-hybrid strategy to identify proteins whose physical interactions with ELF3 were modulated by polyglutamine tract length. Using these two orthogonal approaches, we identify specific genetic interactions and physical mechanisms by which the ELF3 polyglutamine tract may mediate the observed genetic incompatibilities. Our work elucidates how short tandem repeat variation, which is generally underascertained in population-scale sequencing, can contribute to phenotypic variation. Furthermore, our results support our proposal that highly variable STR loci can contribute disproportionately to the epistatic component of heritability.

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