scholarly journals Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates

2020 ◽  
Author(s):  
Amanda K. Broz ◽  
Gus Waneka ◽  
Zhiqiang Wu ◽  
Daniel B. Sloan
Keyword(s):  
De Novo ◽  
Sequence Divergence ◽  
Mutation Rates ◽  
High Fidelity ◽  
Sequence Evolution ◽  
Mitochondrial Mutations ◽  
Mitochondrial Mutation ◽  
Mitochondrial Sequence ◽  
Sequencing Technologies ◽  
Close Relatives

ABSTRACTAlthough plant mitochondrial genomes typically show low rates of sequence evolution, the levels of sequence divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to Silene, an angiosperm genus that exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that S. latifolia maintains low mitochondrial variant frequencies that are comparable to previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica shows much higher variant frequencies, indicating an ongoing bout of elevated mutation rates. Moreover, we found an altered mutational spectrum in S. conica with a heavy bias towards AT→GC transitions (and to a lesser extent AT→CG transversions). We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results indicate that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.

scholarly journals Detecting de novo mitochondrial mutations in angiosperms with highly divergent evolutionary rates

Genetics ◽  
2021 ◽  
Author(s):  
Amanda K Broz ◽  
Gus Waneka ◽  
Zhiqiang Wu ◽  
Matheus Fernandes Gyorfy ◽  
Daniel B Sloan
Keyword(s):  
De Novo ◽  
Sequence Divergence ◽  
Plastid Dna ◽  
Mutation Rates ◽  
High Fidelity ◽  
Sequence Evolution ◽  
De Novo Mutations ◽  
Mitochondrial Mutations ◽  
Mitochondrial Mutation ◽  
Mitochondrial Sequence

Abstract Although plant mitochondrial genomes typically show low rates of sequence evolution, levels of divergence in certain angiosperm lineages suggest anomalously high mitochondrial mutation rates. However, de novo mutations have never been directly analyzed in such lineages. Recent advances in high-fidelity DNA sequencing technologies have enabled detection of mitochondrial mutations when still present at low heteroplasmic frequencies. To date, these approaches have only been performed on a single plant species (Arabidopsis thaliana). Here, we apply a high-fidelity technique (Duplex Sequencing) to multiple angiosperms from the genus Silene, which exhibits extreme heterogeneity in rates of mitochondrial sequence evolution among close relatives. Consistent with phylogenetic evidence, we found that S. latifolia maintains low mitochondrial variant frequencies that are comparable to previous measurements in Arabidopsis. Silene noctiflora also exhibited low variant frequencies despite high levels of historical sequence divergence, which supports other lines of evidence that this species has reverted to lower mitochondrial mutation rates after a past episode of acceleration. In contrast, S. conica showed much higher variant frequencies in mitochondrial (but not in plastid) DNA, consistent with an ongoing bout of elevated mitochondrial mutation rates. Moreover, we found an altered mutational spectrum in S. conica heavily biased towards AT→GC transitions. We also observed an unusually low number of mitochondrial genome copies per cell in S. conica, potentially pointing to reduced opportunities for homologous recombination to accurately repair mismatches in this species. Overall, these results suggest that historical fluctuations in mutation rates are driving extreme variation in rates of plant mitochondrial sequence evolution.

scholarly journals MSH1 is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes

2020 ◽  
Author(s):  
Zhiqiang Wu ◽  
Gus Waneka ◽  
Amanda K. Broz ◽  
Connor R. King ◽  
Daniel B. Sloan
Keyword(s):  
Candidate Genes ◽  
De Novo ◽  
Point Mutations ◽  
Plastid Dna ◽  
Digital Pcr ◽  
Mutation Rates ◽  
Sequence Evolution ◽  
Small Indels ◽  
Plastid Genomes ◽  
Duplex Sequencing

ABSTRACTMitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA, POLIB, MSH1, RECA3, UNG, FPG, and OGG1) for effects on mutation rates in the model angiosperm Arabidopsis thaliana by applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations still at low heteroplasmic frequencies. We find that disrupting MSH1 (but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations in msh1 mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within the mutS mismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses. MSH1 has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

scholarly journals MSH1is required for maintenance of the low mutation rates in plant mitochondrial and plastid genomes

2020 ◽  
Vol 117 (28) ◽  
pp. 16448-16455 ◽  
Author(s):  
Zhiqiang Wu ◽  
Gus Waneka ◽  
Amanda K. Broz ◽  
Connor R. King ◽  
Daniel B. Sloan
Keyword(s):  
Candidate Genes ◽  
De Novo ◽  
Point Mutations ◽  
Plastid Dna ◽  
Digital Pcr ◽  
Mutation Rates ◽  
Sequence Evolution ◽  
Small Indels ◽  
Plastid Genomes ◽  
Duplex Sequencing

Mitochondrial and plastid genomes in land plants exhibit some of the slowest rates of sequence evolution observed in any eukaryotic genome, suggesting an exceptional ability to prevent or correct mutations. However, the mechanisms responsible for this extreme fidelity remain unclear. We tested seven candidate genes involved in cytoplasmic DNA replication, recombination, and repair (POLIA,POLIB,MSH1,RECA3,UNG,FPG, andOGG1) for effects on mutation rates in the model angiospermArabidopsis thalianaby applying a highly accurate DNA sequencing technique (duplex sequencing) that can detect newly arisen mitochondrial and plastid mutations even at low heteroplasmic frequencies. We find that disruptingMSH1(but not the other candidate genes) leads to massive increases in the frequency of point mutations and small indels and changes to the mutation spectrum in mitochondrial and plastid DNA. We also used droplet digital PCR to show transmission of de novo heteroplasmies across generations inmsh1mutants, confirming a contribution to heritable mutation rates. This dual-targeted gene is part of an enigmatic lineage within themutSmismatch repair family that we find is also present outside of green plants in multiple eukaryotic groups (stramenopiles, alveolates, haptophytes, and cryptomonads), as well as certain bacteria and viruses.MSH1has previously been shown to limit ectopic recombination in plant cytoplasmic genomes. Our results point to a broader role in recognition and correction of errors in plant mitochondrial and plastid DNA sequence, leading to greatly suppressed mutation rates perhaps via initiation of double-stranded breaks and repair pathways based on faithful homologous recombination.

scholarly journals Mitochondrial mutations in Caenorhabditis elegans show signatures of oxidative damage and an AT-bias

2021 ◽  
Author(s):  
Gus Waneka ◽  
Joshua M. Svendsen ◽  
Justin C. Havird ◽  
Daniel B. Sloan
Keyword(s):  
Caenorhabditis Elegans ◽  
Oxidative Damage ◽  
De Novo ◽  
Mutation Spectrum ◽  
Mutation Rates ◽  
Mtdna Mutation ◽  
Mitochondrial Mutations ◽  
C Elegans ◽  
Template Strand ◽  
Mtdna Mutations

Rapid mutation rates are typical of mitochondrial genomes (mtDNAs) in animals, but it is not clear why. The difficulty of obtaining measurements of mtDNA mutation that are not biased by natural selection has stymied efforts to distinguish between competing hypotheses about the causes of high mtDNA mutation rates. Several studies which have measured mtDNA mutations in nematodes have yielded small datasets with conflicting conclusions about the relative abundance of different substitution classes (i.e. the mutation spectrum). We therefore leveraged Duplex Sequencing, a high-fidelity DNA sequencing technique, to characterize de novo mtDNA mutations in Caenorhabditis elegans. This approach detected nearly an order of magnitude more mtDNA mutations than documented in any previous nematode mutation study. Despite an existing extreme AT bias in the C. elegans mtDNA (75.6% AT), we found that a significant majority of mutations increase genomic AT content. Compared to some prior studies in nematodes and other animals, the mutation spectrum reported here contains an abundance of CGAT transversions, supporting the hypothesis that oxidative damage may be a driver of mtDNA mutations in nematodes. Further, we found an excess of GT and CT changes on the coding DNA strand relative to the template strand, consistent with increased exposure to oxidative damage. Analysis of the distribution of mutations across the mtDNA revealed significant variation among protein-coding genes and as well as among neighboring nucleotides. This high-resolution view of mitochondrial mutations in C. elegans highlights the value of this system for understanding relationships among oxidative damage, replication error, and mtDNA mutation.

scholarly journals Trevolver: simulating non-reversible DNA sequence evolution in trinucleotide context on a bifurcating tree

2019 ◽  
Author(s):  
Chase W. Nelson ◽  
Yunxin Fu ◽  
Wen-Hsiung Li
Keyword(s):  
Dna Sequence ◽  
De Novo ◽  
Viral Evolution ◽  
Supplementary Information ◽  
Mutation Rates ◽  
Sequence Evolution ◽  
Mutation Model ◽  
Supplementary Material ◽  
Dna Sequence Evolution ◽  
Reversible Mutation

AbstractSummaryRecent de novo mutation data allow the estimation of non-reversible mutation rates for trinucleotide sequence contexts. However, existing tools for simulating DNA sequence evolution are limited to time-reversible models or do not consider trinucleotide context-dependent rates. As this ability is critical to testing evolutionary scenarios under neutrality, we created Trevolver. Sequence evolution is simulated on a bifurcating tree using a 64 × 4 trinucleotide mutation model. Runtime is fast and results match theoretical expectation for CpG sites. Simulations with Trevolver will enable neutral hypotheses to be tested at within-species (polymorphism), between-species (divergence), within-host (e.g., viral evolution), and somatic (e.g., cancer) levels of evolutionary change.Availability and ImplementationTrevolver is implemented in Perl and available on GitHub under GNU General Public License (GPL) version 3 at https://github.com/chasewnelson/[email protected] informationFurther details and example data are available on GitHub.

scholarly journals Mitochondrial mutations in Caenorhabditis elegans show signatures of oxidative damage and an AT-bias

Genetics ◽  
2021 ◽  
Author(s):  
Gus Waneka ◽  
Joshua M Svendsen ◽  
Justin C Havird ◽  
Daniel B Sloan
Keyword(s):  
Caenorhabditis Elegans ◽  
Oxidative Damage ◽  
De Novo ◽  
Mutation Spectrum ◽  
Mutation Rates ◽  
Mtdna Mutation ◽  
Mitochondrial Mutations ◽  
C Elegans ◽  
Template Strand ◽  
Mtdna Mutations

Abstract Rapid mutation rates are typical of mitochondrial genomes (mtDNAs) in animals, but it is not clear why. The difficulty of obtaining measurements of mtDNA mutation that are not biased by natural selection has stymied efforts to distinguish between competing hypotheses about the causes of high mtDNA mutation rates. Several studies which have measured mtDNA mutations in nematodes have yielded small datasets with conflicting conclusions about the relative abundance of different substitution classes (i.e. the mutation spectrum). We therefore leveraged Duplex Sequencing, a high-fidelity DNA sequencing technique, to characterize de novo mtDNA mutations in Caenorhabditis elegans. This approach detected nearly an order of magnitude more mtDNA mutations than documented in any previous nematode mutation study. Despite an existing extreme AT bias in the C. elegans mtDNA (75.6% AT), we found that a significant majority of mutations increase genomic AT content. Compared to some prior studies in nematodes and other animals, the mutation spectrum reported here contains an abundance of CG→AT transversions, supporting the hypothesis that oxidative damage may be a driver of mtDNA mutations in nematodes. Further, we found an excess of G→T and C→T changes on the coding DNA strand relative to the template strand, consistent with increased exposure to oxidative damage. Analysis of the distribution of mutations across the mtDNA revealed significant variation among protein-coding genes and as well as among neighboring nucleotides. This high-resolution view of mitochondrial mutations in C. elegans highlights the value of this system for understanding relationships among oxidative damage, replication error, and mtDNA mutation.

scholarly journals The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Marco Colnaghi ◽  
Andrew Pomiankowski ◽  
Nick Lane
Keyword(s):  
De Novo ◽  
Genetic Diseases ◽  
Primordial Germ Cells ◽  
Evolutionary Model ◽  
Mutation Rates ◽  
Human Populations ◽  
Mitochondrial Mutations ◽  
Germline Development ◽  
High Quality ◽  
Female Germline

Selection against deleterious mitochondrial mutations is facilitated by germline processes, lowering the risk of genetic diseases. How selection works is disputed: experimental data are conflicting and previous modelling work has not clarified the issues. Here we develop computational and evolutionary models that compare the outcome of selection at the level of individuals, cells and mitochondria. Using realistic de novo mutation rates and germline development parameters from mouse and humans, the evolutionary model predicts the observed prevalence of mitochondrial mutations and diseases in human populations. We show the importance of organelle-level selection, seen in the selective pooling of mitochondria into the Balbiani body, in achieving high-quality mitochondria at extreme ploidy in mature oocytes. Alternative mechanisms debated in the literature, bottlenecks and follicular atresia, are unlikely to account for the clinical data, because neither process effectively eliminates mitochondrial mutations under realistic conditions. Our findings explain the major features of female germline architecture, notably the longstanding paradox of over-proliferation of primordial germ cells followed by massive loss. The near-universality of these processes across animal taxa makes sense in light of the need to maintain mitochondrial quality at extreme ploidy in mature oocytes, in the absence of sex and recombination.

scholarly journals Dissecting the chromosome-level genome of the Asian Clam (Corbicula fluminea)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tongqing Zhang ◽  
Jiawen Yin ◽  
Shengkai Tang ◽  
Daming Li ◽  
Xiankun Gu ◽  
...  
Keyword(s):  
De Novo ◽  
Corbicula Fluminea ◽  
Gene Families ◽  
Ruditapes Philippinarum ◽  
Genomic Sequences ◽  
Future Research ◽  
Asian Clam ◽  
Sequencing Technologies ◽  
East And Southeast Asia ◽  
Clam Corbicula

AbstractThe Asian Clam (Corbicula fluminea) is a valuable commercial and medicinal bivalve, which is widely distributed in East and Southeast Asia. As a natural nutrient source, the clam is rich in protein, amino acids, and microelements. The genome of C. fluminea has not yet been characterized; therefore, genome-assisted breeding and improvements cannot yet be implemented. In this work, we present a de novo chromosome-scale genome assembly of C. fluminea using PacBio and Hi-C sequencing technologies. The assembled genome comprised 4728 contigs, with a contig N50 of 521.06 Kb, and 1,215 scaffolds with a scaffold N50 of 70.62 Mb. More than 1.51 Gb (99.17%) of genomic sequences were anchored to 18 chromosomes, of which 1.40 Gb (92.81%) of genomic sequences were ordered and oriented. The genome contains 38,841 coding genes, 32,591 (83.91%) of which were annotated in at least one functional database. Compared with related species, C. fluminea had 851 expanded gene families and 191 contracted gene families. The phylogenetic tree showed that C. fluminea diverged from Ruditapes philippinarum, ~ 228.89 million years ago (Mya), and the genomes of C. fluminea and R. philippinarum shared 244 syntenic blocks. Additionally, we identified 2 MITF members and 99 NLRP members in C. fluminea genome. The high-quality and chromosomal Asian Clam genome will be a valuable resource for a range of development and breeding studies of C. fluminea in future research.

scholarly journals Mitonuclear Coevolution, but Not Nuclear Compensation, Drives Evolution of OXPHOS Complexes in Bivalves

2021 ◽  
Author(s):  
Giovanni Piccinini ◽  
Mariangela Iannello ◽  
Guglielmo Puccio ◽  
Federico Plazzi ◽  
Justin C Havird ◽  
...  
Keyword(s):  
Specific Form ◽  
Nuclear Genes ◽  
Sequence Evolution ◽  
Bivalve Species ◽  
Mitochondrial Mutations ◽  
Site Specific ◽  
Mtdna Inheritance ◽  
Highly Correlated ◽  
Compensation Hypothesis ◽  
Mtdna Variability

Abstract In Metazoa, 4 out of 5 complexes involved in oxidative phosphorylation (OXPHOS) are formed by subunits encoded by both the mitochondrial (mtDNA) and nuclear (nuDNA) genomes, leading to the expectation of mito-nuclear coevolution. Previous studies have supported co-adaptation of mitochondria-encoded (mtOXPHOS) and nuclear-encoded OXPHOS (nuOXPHOS) subunits, often specifically interpreted with regard to the “nuclear compensation hypothesis”, a specific form of mitonuclear coevolution where nuclear genes compensate for deleterious mitochondrial mutations owing to less efficient mitochondrial selection. In this study we analysed patterns of sequence evolution of 79 OXPHOS subunits in 31 bivalve species, a taxon showing extraordinary mtDNA variability and including species with “doubly uniparental” mtDNA inheritance. Our data showed strong and clear signals of mitonuclear coevolution. NuOXPHOS subunits had concordant topologies with mtOXPHOS subunits, contrary to previous phylogenies based on nuclear genes lacking mt interactions. Evolutionary rates between mt and nuOXPHOS subunits were also highly correlated compared to non-OXPHOS-interacting nuclear genes. Nuclear subunits of chimeric OXPHOS complexes (I, III, IV, and V) also had higher dN/dS ratios than Complex II, which is formed exclusively by nuDNA-encoded subunits. However, we did not find evidence of nuclear compensation: mitochondria-encoded subunits showed similar dN/dS ratios compared to nuclear-encoded subunits, contrary to most previously studied bilaterian animals. Moreover, no site-specific signals of compensatory positive selection were detected in nuOXPHOS genes. Our analyses extend the evidence for mitonuclear coevolution to a new taxonomic group, but we propose a reconsideration of the nuclear compensation hypothesis.

scholarly journals De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families

2021 ◽  
Author(s):  
Jonathan R. Belyeu ◽  
Harrison Brand ◽  
Harold Wang ◽  
Xuefang Zhao ◽  
Brent S. Pedersen ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
De Novo ◽  
Mutation Rates ◽  
Structural Mutation
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