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 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 An evolutionary genomic approach reveals both conserved and species-specific genetic elements related to human disease in closely related Aspergillus fungi

Genetics ◽  
2021 ◽  
Author(s):  
Matthew E Mead ◽  
Jacob L Steenwyk ◽  
Lilian P Silva ◽  
Patrícia A de Castro ◽  
Nauman Saeed ◽  
...  
Keyword(s):  
Human Disease ◽  
Evolutionary Rate ◽  
Fungal Disease ◽  
Comparative Genomic ◽  
Genetic Elements ◽  
Genomic Approach ◽  
Evolutionary Genomic ◽  
Repeated Evolution ◽  
Species Specific ◽  
Encoding Genes

Abstract Aspergillosis is an important opportunistic human disease caused by filamentous fungi in the genus Aspergillus. Roughly 70% of infections are caused by Aspergillus fumigatus, with the rest stemming from approximately a dozen other Aspergillus species. Several of these pathogens are closely related to A. fumigatus and belong in the same taxonomic section, section Fumigati. Pathogenic species are frequently most closely related to non-pathogenic ones, suggesting Aspergillus pathogenicity evolved multiple times independently. To understand the repeated evolution of Aspergillus pathogenicity, we performed comparative genomic analyses on 18 strains from 13 species, including 8 species in section Fumigati, which aimed to identify genes, both ones previously connected to virulence as well as ones never before implicated, whose evolution differs between pathogens and non-pathogens. We found that most genes were present in all species, including approximately half of those previously connected to virulence, but a few genes were section- or species-specific. Evolutionary rate analyses identified over 1,700 genes whose evolutionary rate differed between pathogens and non-pathogens and dozens of genes whose rates differed between specific pathogens and the rest of the taxa. Functional testing of deletion mutants of 17 transcription factor-encoding genes whose evolution differed between pathogens and non-pathogens identified eight genes that affect either fungal survival in a model of phagocytic killing, host survival in an animal model of fungal disease, or both. These results suggest that the evolution of pathogenicity in Aspergillus involved both conserved and species-specific genetic elements, illustrating how an evolutionary genomic approach informs the study of fungal disease.

scholarly journals MicroED Structures from Micrometer Thick Protein Crystals

2017 ◽  
Author(s):  
Michael W. Martynowycz ◽  
Calina Glynn ◽  
Jennifer Miao ◽  
M. Jason de la Cruz ◽  
Johan Hattne ◽  
...  
Keyword(s):  
Theoretical Calculations ◽  
Protein Structures ◽  
Atomic Resolution ◽  
Proteinase K ◽  
Protein Crystals ◽  
Molecular Replacement ◽  
Varying Thickness ◽  
Order Of Magnitude ◽  
Human Prion Protein ◽  
Do So

AbstractTheoretical calculations suggest that crystals exceeding 100 nm thickness are excluded by dynamical scattering from successful structure determination using microcrystal electron diffraction (MicroED). These calculations are at odds with experimental results where MicroED structures have been determined from significantly thicker crystals. Here we systematically evaluate the influence of thickness on the accuracy of MicroED intensities and the ability to determine structures from protein crystals one micrometer thick. To do so, we compare ab initio structures of a human prion protein segment determined from thin crystals to those determined from crystals up to one micrometer thick. We also compare molecular replacement solutions from crystals of varying thickness for a larger globular protein, proteinase K. Our results indicate that structures can be reliably determined from crystals at least an order of magnitude thicker than previously suggested by simulation, opening the possibility for an even broader range of MicroED experiments.SummaryAtomic resolution protein structures can be determined by MicroED from crystals that surpass the theoretical maximum thickness limit by an order of magnitude.

scholarly journals Cysteine peptidases and their inhibitors in Tetranychus urticae: a comparative genomic approach

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 307 ◽  
Author(s):  
María Santamaría ◽  
Pedro Hernández-Crespo ◽  
Félix Ortego ◽  
Vojislava Grbic ◽  
Miodrag Grbic ◽  
...  
Keyword(s):  
Tetranychus Urticae ◽  
Comparative Genomic ◽  
Comparative Genomic Approach ◽  
Genomic Approach ◽  
Cysteine Peptidases

1α, 25-Dihydroxyvitamin D3 enables regenerating liver cells to make functional ribonucleotide reductase subunits and replicate DNA in thyroparathyroidectomized rats

1985 ◽  
Vol 63 (5) ◽  
pp. 319-324 ◽  
Author(s):  
T. Youdale ◽  
J. F. Whitfield ◽  
R. H. Rixon
Keyword(s):  
Body Weight ◽  
Dna Replication ◽  
Ribonucleotide Reductase ◽  
Intraperitoneal Injection ◽  
Liver Cells ◽  
Regenerating Liver ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Do So

Between 16 and 20 h after partial (70%) hepatectomy (HPX) in normal rats, the remaining liver cells accumulate ribonucleotide reductase subunits, assemble these into active holoenzyme, and initiate DNA replication. These late prereplicative activities did not occur in most of the liver cells remaining after HPX in rats which had been thyroparathyroidectomized (TPTX) 72 h previously. However, one intraperitoneal injection of 400 or 600 ng 1α, 25-dihydroxyvitamin D3/100 g body weight at the time of HPX enabled the remaining liver cells in such TPTX rats to make functional ribonucleotide reductase subunits, assemble these subunits into active CDP-reducing holoenzymes, and replicate their DNA, though they started to do so 4 to 16 h later than in normal animals.

scholarly journals The Fission Yeast Rad32 (Mre11)-Rad50-Nbs1 Complex Is Required for the S-Phase DNA Damage Checkpoint

2003 ◽  
Vol 23 (18) ◽  
pp. 6564-6573 ◽  
Author(s):  
Charly Chahwan ◽  
Toru M. Nakamura ◽  
Sasirekha Sivakumar ◽  
Paul Russell ◽  
Nicholas Rhind
Keyword(s):  
Dna Damage ◽  
Fission Yeast ◽  
Chromosome Instability ◽  
S Phase ◽  
Comparative Genomic ◽  
Dna Damage Checkpoint ◽  
Checkpoint Signaling ◽  
Damage Repair ◽  
Genomic Approach ◽  
Telomere Regulation

ABSTRACT Mre11, Rad50, and Nbs1 form a conserved heterotrimeric complex that is involved in recombination and DNA damage checkpoints. Mutations in this complex disrupt the S-phase DNA damage checkpoint, the checkpoint which slows replication in response to DNA damage, and cause chromosome instability and cancer in humans. However, how these proteins function and specifically where they act in the checkpoint signaling pathway remain crucial questions. We identified fission yeast Nbs1 by using a comparative genomic approach and showed that the genes for human Nbs1 and fission yeast Nbs1 and that for their budding yeast counterpart, Xrs2, are members of an evolutionarily related but rapidly diverging gene family. Fission yeast Nbs1, Rad32 (the homolog of Mre11), and Rad50 are involved in DNA damage repair, telomere regulation, and the S-phase DNA damage checkpoint. However, they are not required for G2 DNA damage checkpoint. Our results suggest that a complex of Rad32, Rad50, and Nbs1 acts specifically in the S-phase branch of the DNA damage checkpoint and is not involved in general DNA damage recognition or signaling.

scholarly journals Evidence for Active Maintenance of Inverted Repeat Structures Identified by a Comparative Genomic Approach

PLoS ONE ◽  
2007 ◽  
Vol 2 (2) ◽  
pp. e262 ◽  
Author(s):  
Guoyan Zhao ◽  
Kuan Y. Chang ◽  
Katherine Varley ◽  
Gary D. Stormo
Keyword(s):  
Inverted Repeat ◽  
Comparative Genomic ◽  
Active Maintenance ◽  
Comparative Genomic Approach ◽  
Genomic Approach

scholarly journals Comparative Genomics of Regulation of Fatty Acid and Branched-Chain Amino Acid Utilization in Proteobacteria

2008 ◽  
Vol 191 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Alexey E. Kazakov ◽  
Dmitry A. Rodionov ◽  
Eric Alm ◽  
Adam Paul Arkin ◽  
Inna Dubchak ◽  
...  
Keyword(s):  
Glutamate Synthase ◽  
Degradation Pathway ◽  
Transcriptional Factors ◽  
Comparative Genomic ◽  
Isoleucine Leucine ◽  
Dna Motifs ◽  
Regulatory Systems ◽  
Amino Acid Utilization ◽  
Genomic Approach ◽  
Branched Chain

ABSTRACT Bacteria can use branched-chain amino acids (ILV, i.e., isoleucine, leucine, valine) and fatty acids (FAs) as sole carbon and energy sources converting ILV into acetyl-coenzyme A (CoA), propanoyl-CoA, and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR, and GntR families binding to 11 distinct DNA motifs. The ILV degradation genes in gamma- and betaproteobacteria are regulated mainly by a novel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species); in addition, the TetR-type regulator LiuQ was identified in some betaproteobacteria (eight species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gammaproteobacteria (34 species), PsrA in gamma- and betaproteobacteria (45 species), FadP in betaproteobacteria (14 species), and LiuR orthologs in alphaproteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from functional and evolutionary points of view.

scholarly journals Comparative Genomic Analysis of Limosilactobacillus Pontis Reveals Genetic Characteristics of High GC Content and Potential Niches Adaptations

2021 ◽  
Author(s):  
Qing Liu ◽  
Chen Liu ◽  
Weicheng Li ◽  
Wenjun Liu ◽  
Qing Liu
Keyword(s):  
Broiler Chickens ◽  
Gc Content ◽  
Genomic Analysis ◽  
Fermented Milk ◽  
Evolutionary Strategies ◽  
Comparative Genomic ◽  
Genetic Characteristics ◽  
Genomic Approach ◽  
Application Potential ◽  
Carbohydrate Enzymes

Abstract Limosilactobacillus pontis is a species of lactic acid bacteria (LAB) found in fermented milk, sourdough and broiler chickens gastrointestinal tract and so on. However, the evolutionary strategies and genomic characteristics of the species remain unknown, which limits its application. In this study, whole genome sequencing was combined with a comparative genomic approach to investigate genomic characteristics and evolutionary strategies of L. pontis; this includes three published genomic sequences and two strains isolated from fermented milk in Inner Mongolia, China. The mean genome size and GC content of L. pontis was 1.70 Mb and 53.06%, respectively. Within the LAB L. pontis has a high GC content. The phylogenetic tree based on 1,281 core genomes showed that strains from the same sources aggregated together in clusters. Genome information, average nucleotide identity values, and phylogenetic relationships amongst L. pontis from different sources indicated that strains have potential niche adaptability. Functional genomic aspects, GT2 and GT4 (glycosyltransferases, GTs) involved in the synthesis of cellulose and sucrose were the family with the largest number of carbohydrate enzymes in L. pontis, particularly strains isolated from fermented milk. It is worth mentioning that the ability of L. pontis to produce bacteriocin may increase its application potential. This study provides new insight into the genetic characteristics and potential niche adaptations of L. pontis.

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