scholarly journals Pedigree-based measurement of the de novo mutation rate in the gray mouse lemur reveals a high mutation rate, few mutations in CpG sites, and a weak sex bias

2019 ◽  
Author(s):  
C. Ryan Campbell ◽  
George P. Tiley ◽  
Jelmer W. Poelstra ◽  
Kelsie E. Hunnicutt ◽  
Peter A. Larsen ◽  
...  
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
Credible Interval ◽  
Raw Material ◽  
Mouse Lemur ◽  
Primate Species ◽  
De Novo Mutation ◽  
High Coverage ◽  
Cpg Sites ◽  
Gray Mouse Lemur

AbstractSpontaneous germline mutations are the raw material on which evolution acts, and knowledge of their frequency and genomic distribution is crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum of de novo mutations have been directly characterized in only a few lineages. It is therefore critical to expand the phylogenetic scope of these studies to gain a more general understanding of observed mutation rate patterns. Our study provides the first direct mutation rate estimate for a strepsirrhine (i.e., the lemurs and lorises), which comprise nearly half of the primate clade. Using high-coverage linked-read sequencing for a focal quartet of gray mouse lemurs (Microcebus murinus), we estimated the mutation rate to be 1.64 × 10−8 (95% credible interval: 1.41 × 10−8 to 1.98 × 10−8) mutations/site/generation. This estimate is higher than those measured for most previously characterized mammals. Further, we found an unexpectedly low count of paternal mutations, and only a modest overrepresentation of mutations at CpG-sites. Given the surprising nature of these observations, we conducted an independent analysis of context-dependent substitution types for gray mouse lemur and five additional primate species. This analysis yielded patterns consistent with the mutation spectrum from the pedigree mutation-rate analysis, which provides confidence in our ability to accurately identify de novo mutations with our data and bioinformatic filters.

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.

Empirical investigation of mutation rate for herbicide resistance

Weed Science ◽  
2019 ◽  
Vol 67 (4) ◽  
pp. 361-368 ◽  
Author(s):  
Federico A. Casale ◽  
Darci A. Giacomini ◽  
Patrick J. Tranel
Keyword(s):  
Mutation Rate ◽  
Herbicide Resistance ◽  
De Novo ◽  
Selection Process ◽  
Theoretical Calculations ◽  
Acetolactate Synthase ◽  
De Novo Mutation ◽  
De Novo Mutations ◽  
Sources Of Resistance ◽  
Resistant Mutants

AbstractIn a predictable natural selection process, herbicides select for adaptive alleles that allow weed populations to survive. These resistance alleles may be available immediately from the standing genetic variation within the population or may arise from immigration via pollen or seeds from other populations. Moreover, because all populations are constantly generating new mutant genotypes by de novo mutations, resistant mutants may arise spontaneously in any herbicide-sensitive weed population. Recognizing that the relative contribution of each of these three sources of resistance alleles influences what strategies should be applied to counteract herbicide-resistance evolution, we aimed to add experimental information to the resistance evolutionary framework. Specifically, the objectives of this experiment were to determine the de novo mutation rate conferring herbicide resistance in a natural plant population and to test the hypothesis that the mutation rate increases when plants are stressed by sublethal herbicide exposure. We used grain amaranth (Amaranthus hypochondriacus L.) and resistance to acetolactate synthase (ALS)-inhibiting herbicides as a model system to discover spontaneous herbicide-resistant mutants. After screening 70.8 million plants, however, we detected no spontaneous resistant genotypes, indicating the probability of finding a spontaneous ALS-resistant mutant in a given sensitive population is lower than 1.4 × 10−8. This empirically determined upper limit is lower than expected from theoretical calculations based on previous studies. We found no evidence that herbicide stress increased the mutation rate, but were not able to robustly test this hypothesis. The results found in this study indicate that de novo mutations conferring herbicide resistance might occur at lower frequencies than previously expected.

scholarly journals Direct Measure of the De Novo Mutation Rate in Autism and Schizophrenia Cohorts

2010 ◽  
Vol 87 (3) ◽  
pp. 316-324 ◽  
Author(s):  
Philip Awadalla ◽  
Julie Gauthier ◽  
Rachel A. Myers ◽  
Ferran Casals ◽  
Fadi F. Hamdan ◽  
...  
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
De Novo Mutation ◽  
Direct Measure

scholarly journals Antibiotic treatment enhances the genome-wide mutation rate of target cells

2016 ◽  
Vol 113 (18) ◽  
pp. E2498-E2505 ◽  
Author(s):  
Hongan Long ◽  
Samuel F. Miller ◽  
Chloe Strauss ◽  
Chaoxian Zhao ◽  
Lei Cheng ◽  
...  
Keyword(s):  
Mutation Rate ◽  
De Novo ◽  
De Novo Mutation ◽  
Target Cells ◽  
Invasive Pathogens ◽  
Dna Mismatch ◽  
Damage Repair ◽  
Genome Wide ◽  
Enhanced Expression

Although it is well known that microbial populations can respond adaptively to challenges from antibiotics, empirical difficulties in distinguishing the roles of de novo mutation and natural selection have left several issues unresolved. Here, we explore the mutational properties ofEscherichia coliexposed to long-term sublethal levels of the antibiotic norfloxacin, using a mutation accumulation design combined with whole-genome sequencing of replicate lines. The genome-wide mutation rate significantly increases with norfloxacin concentration. This response is associated with enhanced expression of error-prone DNA polymerases and may also involve indirect effects of norfloxacin on DNA mismatch and oxidative-damage repair. Moreover, we find that acquisition of antibiotic resistance can be enhanced solely by accelerated mutagenesis, i.e., without direct involvement of selection. Our results suggest that antibiotics may generally enhance the mutation rates of target cells, thereby accelerating the rate of adaptation not only to the antibiotic itself but to additional challenges faced by invasive pathogens.

scholarly journals Pedigree-based and phylogenetic methods support surprising patterns of mutation rate and spectrum in the gray mouse lemur

Heredity ◽  
2021 ◽  
Author(s):  
C. Ryan Campbell ◽  
George P. Tiley ◽  
Jelmer W. Poelstra ◽  
Kelsie E. Hunnicutt ◽  
Peter A. Larsen ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Mouse Lemur ◽  
Phylogenetic Methods ◽  
Gray Mouse Lemur

scholarly journals De novo mutation rates at the single-mutation resolution in a human HBB gene-region associated with adaptation and genetic disease

2022 ◽  
pp. gr.276103.121
Author(s):  
Daniel Melamed ◽  
Yuval Nov ◽  
Assaf Malik ◽  
Michael B Yakass ◽  
Evgeni Bolotin ◽  
...  
Keyword(s):  
Mutation Rate ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Region Of Interest ◽  
De Novo Mutation ◽  
Mutation Rates ◽  
Single Mutation ◽  
Random Mutation ◽  
Genome Wide ◽  
Specific Manner

While it is known that the mutation rate varies across the genome, previous estimates were based on averaging across various numbers of positions. Here we describe a method to measure the origination rates of target mutations at target base positions and apply it to a 6-bp region in the human hemoglobin subunit beta (HBB) gene and to the identical, paralogous hemoglobin subunit delta (HBD) region in sperm cells from both African and European donors. The HBB region of interest (ROI) includes the site of the hemoglobin S (HbS) mutation, which protects against malaria, is common in Africa and has served as a classic example of adaptation by random mutation and natural selection. We found a significant correspondence between de novo mutation rates and past observations of alleles in carriers, showing that mutation rates vary substantially in a mutation-specific manner that contributes to the site frequency spectrum. We also found that the overall point mutation rate is significantly higher in Africans than in Europeans in the HBB region studied. Finally, the rate of the 20A→T mutation, called the 'HbS mutation' when it appears in HBB, is significantly higher than expected from the genome-wide average for this mutation type. Nine instances were observed in the African HBB ROI, where it is of adaptive significance, representing at least three independent originations; no instances were observed elsewhere. Further studies will be needed to examine mutation rates at the single-mutation resolution across these and other loci and organisms and to uncover the molecular mechanisms responsible.

scholarly journals Revisiting the evolutionary history of pigs via de novo mutation rate estimation by deep genome sequencing on a three-generation pedigree

2021 ◽  
Author(s):  
Mingpeng Zhang ◽  
Qiang Yang ◽  
Huashui Ai ◽  
Lusheng Huang
Keyword(s):  
Genome Sequencing ◽  
Mutation Rate ◽  
Evolutionary History ◽  
North China ◽  
De Novo ◽  
Yellow River ◽  
De Novo Mutation ◽  
Whole Genome Sequencing Data ◽  
Hetao Plain ◽  
History Of

The mutation rate used in the previous analyses of pig evolution and demographics was cursory and brought potential bias in inferring the evolutionary history of pig, an essential domesticated agricultural animal. Herein, we estimated de novo mutation rate of pigs using high-quality whole-genome sequencing data from nine individuals in a three-generation pedigree through stringent filtering and validation. The estimated mutation rate was 3.6 × 10−9 per site per generation, corresponding to 1.2 × 10−9 per site per year. Using this mutation rate, we re-investigated the evolutionary history of pigs. Our estimates agreed to the divergence time of ~10 kiloyears ago (Kya) between European wild and domesticated pigs, which was consistent with the domestication time of European pigs based on archaeological evidence. However, other divergence events inferred here were not as ancient as previously described. Our estimates suggested that: Sus speciation occurred ~1.36 Million years ago (Mya); European pigs split up with Asian ones only around 219 Kya; South and North Chinese wild boars split about 25 Kya. Meanwhile, our results showed that the most recent divergence event between Chinese wild and domesticated pigs occurred in the Hetao plain, North China, approximately 20 Kya, supporting the possibly independent domestication in North China along the middle Yellow River. We also found the maximum effective population size of pigs was ~6 times larger than the previous estimate. Notably by simulation, we confirmed an archaic migration from other Sus species originating ~2 Mya to European pigs during western colonization of pigs, which possibly interfered with the previous demographic inference. Our findings advance the understanding of pig evolutionary history.

scholarly journals A mutational hotspot that determines highly repeatable evolution can be built and broken by silent genetic changes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
James S. Horton ◽  
Louise M. Flanagan ◽  
Robert W. Jackson ◽  
Nicholas K. Priest ◽  
Tiffany B. Taylor
Keyword(s):  
Genetic Variation ◽  
Pseudomonas Fluorescens ◽  
Mutation Rate ◽  
De Novo ◽  
De Novo Mutation ◽  
Rate Heterogeneity ◽  
Genetic Changes ◽  
Evolutionary Forces ◽  
Mutational Hotspots ◽  
Minimal Media

AbstractMutational hotspots can determine evolutionary outcomes and make evolution repeatable. Hotspots are products of multiple evolutionary forces including mutation rate heterogeneity, but this variable is often hard to identify. In this work, we reveal that a near-deterministic genetic hotspot can be built and broken by a handful of silent mutations. We observe this when studying homologous immotile variants of the bacteria Pseudomonas fluorescens, AR2 and Pf0-2x. AR2 resurrects motility through highly repeatable de novo mutation of the same nucleotide in >95% lines in minimal media (ntrB A289C). Pf0-2x, however, evolves via a number of mutations meaning the two strains diverge significantly during adaptation. We determine that this evolutionary disparity is owed to just 6 synonymous variations within the ntrB locus, which we demonstrate by swapping the sites and observing that we are able to both break (>95% to 0%) and build (0% to 80%) a deterministic mutational hotspot. Our work reveals a key role for silent genetic variation in determining adaptive outcomes.

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