scholarly journals Estimating Mutation Rate: How to Count Mutations?

Genetics ◽  
2003 ◽  
Vol 164 (2) ◽  
pp. 797-805
Author(s):  
Yun-Xin Fu ◽  
Haying Huai
Keyword(s):  
Mutation Rate ◽  
Genetic Research ◽  
Accurate Estimate ◽  
General Strategy ◽  
Direct Estimate ◽  
Pairwise Correlation ◽  
Essential Parameter ◽  
Order Of Magnitude ◽  
Independent Mutation ◽  
Mutation Rate Estimate

Abstract Mutation rate is an essential parameter in genetic research. Counting the number of mutant individuals provides information for a direct estimate of mutation rate. However, mutant individuals in the same family can share the same mutations due to premeiotic mutation events, so that the number of mutant individuals can be significantly larger than the number of mutation events observed. Since mutation rate is more closely related to the number of mutation events, whether one should count only independent mutation events or the number of mutants remains controversial. We show in this article that counting mutant individuals is a correct approach for estimating mutation rate, while counting only mutation events will result in underestimation. We also derived the variance of the mutation-rate estimate, which allows us to examine a number of important issues about the design of such experiments. The general strategy of such an experiment should be to sample as many families as possible and not to sample much more offspring per family than the reciprocal of the pairwise correlation coefficient within each family. To obtain a reasonably accurate estimate of mutation rate, the number of sampled families needs to be in the same or higher order of magnitude as the reciprocal of the mutation rate.

scholarly journals Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site

Heredity ◽  
2020 ◽  
Vol 126 (1) ◽  
pp. 107-116
Author(s):  
Jobran Chebib ◽  
Benjamin C. Jackson ◽  
Eugenio López-Cortegano ◽  
Diethard Tautz ◽  
Peter D. Keightley
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
Inbred Mice ◽  
Genetic Research ◽  
Inbred Strains ◽  
Genetics Research ◽  
Novel Approach ◽  
Nucleotide Mutation ◽  
Commercial Breeder ◽  
Mutation Rate Estimate

AbstractFor over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10−9 in C3H/HeN), but substantially inflated estimates when mice come from production colonies.

scholarly journals On the Rate and Linearity of Viability Declines in Drosophila Mutation-Accumulation Experiments: Genomic Mutation Rates and Synergistic Epistasis Revisited

Genetics ◽  
2004 ◽  
Vol 166 (2) ◽  
pp. 797-806 ◽  
Author(s):  
James D Fry
Keyword(s):  
Mutation Rate ◽  
Average Rate ◽  
Natural Populations ◽  
Mutation Accumulation ◽  
High Rate ◽  
Deleterious Mutations ◽  
Order Of Magnitude ◽  
Contamination Event ◽  
Genomic Mutation ◽  
The 1960S

Abstract High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others’ effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi’s experiment as well as in Mukai’s, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai’s estimate of the genomic mutation rate is supported, that from Ohnishi’s experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai’s experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

scholarly journals Direct estimate of the spontaneous mutation rate uncovers the effects of drift and recombination in theChlamydomonas reinhardtiiplastid genome

2015 ◽  
Author(s):  
Rob W Ness ◽  
Susanne A Kraemer ◽  
Nick Colegrave ◽  
Peter D Keightley
Keyword(s):  
Mutation Rate ◽  
Genetic Drift ◽  
Plastid Genome ◽  
De Novo ◽  
Spontaneous Mutation ◽  
Genome Structure ◽  
Nuclear Genome ◽  
De Novo Mutation ◽  
Direct Estimate ◽  
Plastid Genomes

Plastids perform crucial cellular functions, including photosynthesis, across a wide variety of eukaryotes. Since endosymbiosis, plastids have maintained independent genomes that now display a wide diversity of gene content, genome structure, gene regulation mechanisms, and transmission modes. The evolution of plastid genomes depends on an input ofde novomutation, but our knowledge of mutation in the plastid is limited to indirect inference from patterns of DNA divergence between species. Here, we use a mutation accumulation experiment, where selection acting on mutations is rendered ineffective, combined with whole-plastid genome sequencing to directly characterize de novo mutation inChlamydomonas reinhardtii. We show that the mutation rates of the plastid and nuclear genomes are similar, but that the base spectra of mutations differ significantly. We integrate our measure of the mutation rate with a population genomic dataset of 20 individuals, and show that the plastid genome is subject to substantially stronger genetic drift than the nuclear genome. We also show that high levels of linkage disequilibrium in the plastid genome are not due to restricted recombination, but are instead a consequence of increased genetic drift. One likely explanation for increased drift in the plastid genome is that there are stronger effects of genetic hitchhiking. The presence of recombination in the plastid is consistent with laboratory studies inC. reinhardtiiand demonstrates that although the plastid genome is thought to be uniparentally inherited, it recombines in nature at a rate similar to the nuclear genome.

scholarly journals Effects of DNA oxidation on the evolution of genomes

2017 ◽  
Author(s):  
Michael Sheinman ◽  
Rutger Hermsen
Keyword(s):  
Dna Replication ◽  
Mutation Rate ◽  
Dna Oxidation ◽  
Comparative Genomic ◽  
Computational Studies ◽  
Mutational Spectrum ◽  
Genomic Approach ◽  
Order Of Magnitude ◽  
Evolution Of Genomes ◽  
Do So

Oxidation of DNA increases its mutation rate, causing otherwise rare G → T transversions during DNA replication. Here we use a comparative genomic approach to assess the importance of DNA oxidation for the evolution of genomic sequences. To do so, we study the mutational spectrum of Gn-tracks on various timescales, ranging from one human generation to the divergence between primates, and compare it to the properties of guanines oxidation known from experimental and computational studies. Our results suggest that, in short Gntracks (n≤ 3), oxidation does not dominate the mutagenesis of guanines, except in cancerous tumors, especially in lungs. However, we consistently find that the G → T transversion rate is elevated by an order of magnitude in long Gntracks (n≳ 6). In such long Gn-tracks, G → T substitutions in fact dominate the mutational spectrum, suggesting that long Gntracks are oxidized more frequently and/or repaired less efficiently.

scholarly journals Upper-limit mutation rate estimation for a plant RNA virus

2009 ◽  
Vol 5 (3) ◽  
pp. 394-396 ◽  
Author(s):  
Rafael Sanjuán ◽  
Patricia Agudelo-Romero ◽  
Santiago F. Elena
Keyword(s):  
Mutation Rate ◽  
Rna Viruses ◽  
Rna Virus ◽  
Plant Viruses ◽  
Mutation Rates ◽  
Methodological Error ◽  
Direct Estimate ◽  
Rate Estimation ◽  
Mutation Rate Estimation

It is generally accepted that mutation rates of RNA viruses are inherently high due to the lack of proofreading mechanisms. However, direct estimates of mutation rate are surprisingly scarce, in particular for plant viruses. Here, based on the analysis of in vivo mutation frequencies in tobacco etch virus , we calculate an upper-bound mutation rate estimation of 3×10 −5 per site and per round of replication; a value which turns out to be undistinguishable from the methodological error. Nonetheless, the value is barely on the lower side of the range accepted for RNA viruses, although in good agreement with the only direct estimate obtained for other plant viruses. These observations suggest that, perhaps, differences in the selective pressures operating during plant virus evolution may have driven their mutation rates towards values lower than those characteristic of other RNA viruses infecting bacteria or animals.

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