scholarly journals Variable Spontaneous Mutation and Loss of Heterozygosity among Heterozygous Genomes in Yeast

2020 ◽  
Vol 37 (11) ◽  
pp. 3118-3130 ◽  
Author(s):  
Duong T Nguyen ◽  
Baojun Wu ◽  
Hongan Long ◽  
Nan Zhang ◽  
Caitlyn Patterson ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Yeast Species ◽  
Spontaneous Mutation ◽  
Mutation Accumulation ◽  
Primary Sources ◽  
Mutation Rates ◽  
Substantial Variation ◽  
Heterozygous Site ◽  
Genome Wide ◽  
Mutation Spectra

Abstract Mutation and recombination are the primary sources of genetic variation. To better understand the evolution of genetic variation, it is crucial to comprehensively investigate the processes involving mutation accumulation and recombination. In this study, we performed mutation accumulation experiments on four heterozygous diploid yeast species in the Saccharomycodaceae family to determine spontaneous mutation rates, mutation spectra, and losses of heterozygosity (LOH). We observed substantial variation in mutation rates and mutation spectra. We also observed high LOH rates (1.65–11.07×10−6 events per heterozygous site per cell division). Biases in spontaneous mutation and LOH together with selection ultimately shape the variable genome-wide nucleotide landscape in yeast species.

scholarly journals Nature of Deleterious Mutation Load in Drosophila

Genetics ◽  
1996 ◽  
Vol 144 (4) ◽  
pp. 1993-1999 ◽  
Author(s):  
Peter D Keightley
Keyword(s):  
Deleterious Mutation ◽  
Spontaneous Mutation ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Mutation Load ◽  
Spontaneous Mutation Rate ◽  
A Minor ◽  
Chromosome I ◽  
Balancer Chromosomes ◽  
Balancer Chromosome

Much population genetics and evolution theory depends on knowledge of genomic mutation rates and distributions of mutation effects for fitness, but most information comes from a few mutation accumulation experiments in Drosophila in which replicated chromosomes are sheltered from natural selection by a balancer chromosome. I show here that data from these experiments imply the existence of a large class of minor viability mutations with approximately equivalent effects. However, analysis of the distribution of viabilities of chromosomes exposed to EMS mutagenesis reveals a qualitatively different distribution of effects lacking such a minor effects class. A possible explanation for this difference is that transposable element insertions, a common class of spontaneous mutation event in Drosophila, frequently generate minor viability effects. This explanation would imply that current estimates of deleterious mutation rates are not generally applicable in evolutionary models, as transposition rates vary widely. Alternatively, much of the apparent decline in viability under spontaneous mutation accumulation could have been nonmutational, perhaps due to selective improvement of balancer chromosomes. This explanation accords well with the data and implies a spontaneous mutation rate for viability two orders of magnitude lower than previously assumed, with most mutation load attributable to major effects.

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 De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population

2019 ◽  
Author(s):  
Michael D. Kessler ◽  
Douglas P. Loesch ◽  
James A. Perry ◽  
Nancy L. Heard-Costa ◽  
Brian E. Cade ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
De Novo ◽  
Population Level ◽  
Mutation Rates ◽  
Founder Population ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Nucleotide Mutation ◽  
Rare Genetic Variation

Abstractde novo Mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) program, we directly estimate and analyze DNM counts, rates, and spectra from 1,465 trios across an array of diverse human populations. Using the resulting call set of 86,865 single nucleotide DNMs, we find a significant positive correlation between local recombination rate and local DNM rate, which together can explain up to 35.5% of the genome-wide variation in population level rare genetic variation from 41K unrelated TOPMed samples. While genome-wide heterozygosity does correlate weakly with DNM count, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, interestingly, we do find significantly fewer DNMs in Amish individuals compared with other Europeans, even after accounting for parental age and sequencing center. Specifically, we find significant reductions in the number of T→C mutations in the Amish, which seems to underpin their overall reduction in DNMs. Finally, we calculate near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by non-additive genetic effects and/or the environment, and that a less mutagenic environment may be responsible for the reduced DNM rate in the Amish.SignificanceHere we provide one of the largest and most diverse human de novo mutation (DNM) call sets to date, and use it to quantify the genome-wide relationship between local mutation rate and population-level rare genetic variation. While we demonstrate that the human single nucleotide mutation rate is similar across numerous human ancestries and populations, we also discover a reduced mutation rate in the Amish founder population, which shows that mutation rates can shift rapidly. Finally, we find that variation in mutation rates is not heritable, which suggests that the environment may influence mutation rates more significantly than previously realized.

scholarly journals Temperature-dependence of spontaneous mutation rates

2020 ◽  
Author(s):  
Ann-Marie Waldvogel ◽  
Markus Pfenninger
Keyword(s):  
Genetic Variation ◽  
Null Hypothesis ◽  
Spontaneous Mutation ◽  
Empirical Support ◽  
Mutation Rates ◽  
Temperature Extremes ◽  
Whole Genome ◽  
Direct Impact ◽  
Species Specific ◽  
Dependent Processes

Mutation is the source of genetic variation and the fundament of evolution. At the interphase of ecology and evolution, temperature has long been suggested to have a direct impact on realised spontaneous mutation rates. The question is whether mutation rates can be a species-specific constant under variable environmental conditions, such as variation of the ambient temperature. By combining mutation accumulation with whole genome sequencing in a multicellular organism, we provide empirical support to reject this null hypothesis. Instead mutation rates depend on temperature in a U-shaped manner with increasing rates towards both temperature extremes. This relation has important implications for mutation dependent processes in molecular evolution, processes shaping the evolution of mutation rates and even the evolution of biodiversity as such.

scholarly journals Spontaneous Mutational Variation for Body Size inCaenorhabditis elegans

Genetics ◽  
2002 ◽  
Vol 162 (2) ◽  
pp. 755-765 ◽  
Author(s):  
Ricardo B R Azevedo ◽  
Peter D Keightley ◽  
Camilla Laurén-Määttä ◽  
Larissa L Vassilieva ◽  
Michael Lynch ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Body Size ◽  
Spontaneous Mutation ◽  
C Elegans ◽  
Genome Wide ◽  
Increase Body Size ◽  
The Impact ◽  
Mutational Variance ◽  
Selection Of ◽  
New Mutations

AbstractWe measured the impact of new mutations on genetic variation for body size in two independent sets of C. elegans spontaneous mutation-accumulation (MA) lines, derived from the N2 strain, that had been maintained by selfing for 60 or 152 generations. The two sets of lines gave broadly consistent results. The change of among-line genetic variation between cryopreserved controls and the MA lines implied that broad sense heritability increased by 0.4% per generation. Overall, MA reduced mean body size by ∼0.1% per generation. The genome-wide rate for mutations with detectable effects on size was estimated to be ∼0.0025 per haploid genome per generation, and their mean effects were ∼20%. The proportion of mutations that increase body size was estimated by maximum likelihood to be no more than 20%, suggesting that the amount of mutational variation available for selection for increased size could be quite small. This hypothesis was supported by an artificial selection experiment on adult body size, started from a single highly inbred N2 individual. We observed a strongly asymmetrical response to selection of a magnitude consistent with the input of mutational variance observed in the MA experiment.

scholarly journals High and Highly Variable Spontaneous Mutation Rates in Daphnia

2020 ◽  
Vol 37 (11) ◽  
pp. 3258-3266 ◽  
Author(s):  
Eddie K H Ho ◽  
Fenner Macrae ◽  
Leigh C Latta ◽  
Peter McIlroy ◽  
Dieter Ebert ◽  
...  
Keyword(s):  
Intraspecific Variation ◽  
Sequence Data ◽  
Spontaneous Mutation ◽  
Nuclear Genome ◽  
Mutation Accumulation ◽  
Whole Genome Sequence ◽  
Critical Parameters ◽  
Mutation Rates ◽  
Base Substitution ◽  
Conversion Rates

Abstract The rate and spectrum of spontaneous mutations are critical parameters in basic and applied biology because they dictate the pace and character of genetic variation introduced into populations, which is a prerequisite for evolution. We use a mutation–accumulation approach to estimate mutation parameters from whole-genome sequence data from multiple genotypes from multiple populations of Daphnia magna, an ecological and evolutionary model system. We report extremely high base substitution mutation rates (µ-n,bs = 8.96 × 10−9/bp/generation [95% CI: 6.66–11.97 × 10−9/bp/generation] in the nuclear genome and µ-m,bs = 8.7 × 10−7/bp/generation [95% CI: 4.40–15.12 × 10−7/bp/generation] in the mtDNA), the highest of any eukaryote examined using this approach. Levels of intraspecific variation based on the range of estimates from the nine genotypes collected from three populations (Finland, Germany, and Israel) span 1 and 3 orders of magnitude, respectively, resulting in up to a ∼300-fold difference in rates among genomic partitions within the same lineage. In contrast, mutation spectra exhibit very consistent patterns across genotypes and populations, suggesting the mechanisms underlying the mutational process may be similar, even when the rates at which they occur differ. We discuss the implications of high levels of intraspecific variation in rates, the importance of estimating gene conversion rates using a mutation–accumulation approach, and the interacting factors influencing the evolution of mutation parameters. Our findings deepen our knowledge about mutation and provide both challenges to and support for current theories aimed at explaining the evolution of the mutation rate, as a trait, across taxa.

scholarly journals Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 363
Author(s):  
Sulochana K. Wasala ◽  
Dana K. Howe ◽  
Louise-Marie Dandurand ◽  
Inga A. Zasada ◽  
Dee R. Denver
Keyword(s):  
Genetic Variation ◽  
Potato Production ◽  
Globodera Pallida ◽  
Fixation Index ◽  
Parasitic Nematodes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Field Samples ◽  
Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

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