scholarly journals Low base-substitution mutation rate in the germline genome of the ciliate Tetrahymena thermophila

2015 ◽  
Author(s):  
Hongan Long ◽  
David J. Winter ◽  
Allan Y.-C Chang ◽  
Way Sung ◽  
Steven H. Wu ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Tetrahymena Thermophila ◽  
Mutation Rates ◽  
Base Substitution ◽  
Paramecium Tetraurelia ◽  
Epigenetic Factors ◽  
Detection Approach ◽  
Evolution Experiment ◽  
Substitution Mutations ◽  
Substitution Mutation

AbstractMutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 × 10−12 per site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the “visible” mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.

scholarly journals Low Base-Substitution Mutation Rate but High Rate of Slippage Mutations in the Sequence Repeat-Rich Genome of Dictyostelium discoideum

2020 ◽  
Vol 10 (9) ◽  
pp. 3445-3452
Author(s):  
Sibel Kucukyildirim ◽  
Megan Behringer ◽  
Way Sung ◽  
Debra A Brock ◽  
Thomas G Doak ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Mutation Rate ◽  
Simple Sequence Repeats ◽  
Model Organism ◽  
High Rate ◽  
Base Substitution ◽  
Paramecium Tetraurelia ◽  
Effective Population ◽  
Simple Sequence ◽  
Substitution Mutation

Abstract We describe the rate and spectrum of spontaneous mutations for the social amoeba Dictyostelium discoideum, a key model organism in molecular, cellular, evolutionary and developmental biology. Whole-genome sequencing of 37 mutation accumulation lines of D. discoideum after an average of 1,500 cell divisions yields a base-substitution mutation rate of 2.47 × 10−11 per site per generation, substantially lower than that of most eukaryotic and prokaryotic organisms, and of the same order of magnitude as in the ciliates Paramecium tetraurelia and Tetrahymena thermophila. Known for its high genomic AT content and abundance of simple sequence repeats, we observe that base-substitution mutations in D. discoideum are highly A/T biased. This bias likely contributes both to the high genomic AT content and to the formation of simple sequence repeats in the AT-rich genome of Dictyostelium discoideum. In contrast to the situation in other surveyed unicellular eukaryotes, indel rates far exceed the base-substitution mutation rate in this organism with a high proportion of 3n indels, particularly in regions without simple sequence repeats. Like ciliates, D. discoideum has a large effective population size, reducing the power of random genetic drift, magnifying the effect of selection on replication fidelity, in principle allowing D. discoideum to evolve an extremely low base-substitution mutation rate.

scholarly journals Periodic variation of mutation rates in bacterial genomes associated with replication timing

2017 ◽  
Author(s):  
Marcus M. Dillon ◽  
Way Sung ◽  
Michael Lynch ◽  
Vaughn S. Cooper
Keyword(s):  
Vibrio Fischeri ◽  
Bacterial Species ◽  
Replication Timing ◽  
Small Chromosome ◽  
Burkholderia Cenocepacia ◽  
Mutation Rates ◽  
Base Substitution ◽  
Large Chromosome ◽  
Bacterial Genomes ◽  
Substitution Mutation

ABSTRACTThe causes and consequences of spatiotemporal variation in mutation rates remains to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes:Vibrio fischeri, Vibrio cholerae, andBurkholderia cenocepacia. Following five evolution experiments with these bacteria conducted in the near-absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base-substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosome ofV. fischeriandV. cholerae, where concurrently replicated regions experience similar base-substitution mutation rates. The base-substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates as the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base-substitution rates, which along with the inferred ~800 Kb wave period suggests that the source of the periodicity is not sequence-specific but rather a systematic process related to the cell cycle. These results support the notion that base-substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load.

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 Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree

2009 ◽  
Vol 19 (17) ◽  
pp. 1453-1457 ◽  
Author(s):  
Yali Xue ◽  
Qiuju Wang ◽  
Quan Long ◽  
Bee Ling Ng ◽  
Harold Swerdlow ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Mutation Rate ◽  
Direct Sequencing ◽  
Base Substitution ◽  
Substitution Mutation ◽  
Human Y Chromosome

scholarly journals Spontaneous mutation rate estimates for the principal malaria vectors Anopheles coluzzii and Anopheles stephensi

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Iliyas Rashid ◽  
Melina Campos ◽  
Travis Collier ◽  
Marc Crepeau ◽  
Allison Weakley ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Mutation Rate ◽  
Anopheles Stephensi ◽  
Spontaneous Mutation ◽  
False Negative ◽  
False Negative Rate ◽  
Mutation Rates ◽  
Malaria Vectors ◽  
Base Substitution ◽  
Anopheles Coluzzii

AbstractUsing high-depth whole genome sequencing of F0 mating pairs and multiple individual F1 offspring, we estimated the nuclear mutation rate per generation in the malaria vectors Anopheles coluzzii and Anopheles stephensi by detecting de novo genetic mutations. A purpose-built computer program was employed to filter actual mutations from a deep background of superficially similar artifacts resulting from read misalignment. Performance of filtering parameters was determined using software-simulated mutations, and the resulting estimate of false negative rate was used to correct final mutation rate estimates. Spontaneous mutation rates by base substitution were estimated at 1.00 × 10−9 (95% confidence interval, 2.06 × 10−10—2.91 × 10−9) and 1.36 × 10−9 (95% confidence interval, 4.42 × 10−10—3.18 × 10−9) per site per generation in A. coluzzii and A. stephensi respectively. Although similar studies have been performed on other insect species including dipterans, this is the first study to empirically measure mutation rates in the important genus Anopheles, and thus provides an estimate of µ that will be of utility for comparative evolutionary genomics, as well as for population genetic analysis of malaria vector mosquito species.

scholarly journals Escherichia coli with a Tunable Point Mutation Rate for Evolution Experiments

2020 ◽  
Vol 10 (8) ◽  
pp. 2671-2681 ◽  
Author(s):  
Nicholas A. Sherer ◽  
Thomas E. Kuhlman
Keyword(s):  
Escherichia Coli ◽  
Point Mutation ◽  
Mutation Rate ◽  
Fitness Landscape ◽  
Genetically Engineered ◽  
Mutation Rates ◽  
Nucleotide Polymorphisms ◽  
Beneficial Mutations ◽  
Beneficial Effects ◽  
Evolution Experiment

The mutation rate and mutations’ effects on fitness are crucial to evolution. Mutation rates are under selection due to linkage between mutation rate modifiers and mutations’ effects on fitness. The linkage between a higher mutation rate and more beneficial mutations selects for higher mutation rates, while the linkage between a higher mutation rate and more deleterious mutations selects for lower mutation rates. The net direction of selection on mutations rates depends on the fitness landscape, and a great deal of work has elucidated the fitness landscapes of mutations. However, tests of the effect of varying a mutation rate on evolution in a single organism in a single environment have been difficult. This has been studied using strains of antimutators and mutators, but these strains may differ in additional ways and typically do not allow for continuous variation of the mutation rate. To help investigate the effects of the mutation rate on evolution, we have genetically engineered a strain of Escherichia coli with a point mutation rate that can be smoothly varied over two orders of magnitude. We did this by engineering a strain with inducible control of the mismatch repair proteins MutH and MutL. We used this strain in an approximately 350 generation evolution experiment with controlled variation of the mutation rate. We confirmed the construct and the mutation rate were stable over this time. Sequencing evolved strains revealed a higher number of single nucleotide polymorphisms at higher mutations rates, likely due to either the beneficial effects of these mutations or their linkage to beneficial mutations.

scholarly journals Periodic Variation of Mutation Rates in Bacterial Genomes Associated with Replication Timing

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Marcus M. Dillon ◽  
Way Sung ◽  
Michael Lynch ◽  
Vaughn S. Cooper
Keyword(s):  
Bacterial Species ◽  
Replication Timing ◽  
Burkholderia Cenocepacia ◽  
Mutation Rates ◽  
Base Substitution ◽  
Large Chromosome ◽  
Rate Variation ◽  
Bacterial Genomes ◽  
Content Type ◽  
Substitution Mutation

ABSTRACT The causes and consequences of spatiotemporal variation in mutation rates remain to be explored in nearly all organisms. Here we examine relationships between local mutation rates and replication timing in three bacterial species whose genomes have multiple chromosomes: Vibrio fischeri, Vibrio cholerae, and Burkholderia cenocepacia. Following five mutation accumulation experiments with these bacteria conducted in the near absence of natural selection, the genomes of clones from each lineage were sequenced and analyzed to identify variation in mutation rates and spectra. In lineages lacking mismatch repair, base substitution mutation rates vary in a mirrored wave-like pattern on opposing replichores of the large chromosomes of V. fischeri and V. cholerae, where concurrently replicated regions experience similar base substitution mutation rates. The base substitution mutation rates on the small chromosome are less variable in both species but occur at similar rates to those in the concurrently replicated regions of the large chromosome. Neither nucleotide composition nor frequency of nucleotide motifs differed among regions experiencing high and low base substitution rates, which along with the inferred ~800-kb wave period suggests that the source of the periodicity is not sequence specific but rather a systematic process related to the cell cycle. These results support the notion that base substitution mutation rates are likely to vary systematically across many bacterial genomes, which exposes certain genes to elevated deleterious mutational load. IMPORTANCE That mutation rates vary within bacterial genomes is well known, but the detailed study of these biases has been made possible only recently with contemporary sequencing methods. We applied these methods to understand how bacterial genomes with multiple chromosomes, like those of Vibrio and Burkholderia, might experience heterogeneous mutation rates because of their unusual replication and the greater genetic diversity found on smaller chromosomes. This study captured thousands of mutations and revealed wave-like rate variation that is synchronized with replication timing and not explained by sequence context. The scale of this rate variation over hundreds of kilobases of DNA strongly suggests that a temporally regulated cellular process may generate wave-like variation in mutation risk. These findings add to our understanding of how mutation risk is distributed across bacterial and likely also eukaryotic genomes, owing to their highly conserved replication and repair machinery.

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