scholarly journals Temporal stability and genetic diversity of 48-year old T-series phages

2020 ◽  
Author(s):  
Dinesh Subedi ◽  
Jeremy J. Barr
Keyword(s):  
Molecular Biology ◽  
Genetic Drift ◽  
Genetic Relatedness ◽  
Temporal Stability ◽  
Genomic Analysis ◽  
Model Organisms ◽  
Phenotypic Differences ◽  
Genomic Changes ◽  
Ncbi Refseq ◽  
Phenotypic Variations

AbstractT-series phages have been model organisms for molecular biology since the 1940s. Given that these phages have been stocked, distributed, and propagated for decades across the globe, there exists the potential for genetic drift to accumulate between stocks over time. Here we compared the temporal stability and genetic relatedness of laboratory-maintained phage stocks with a T-series collection from 1972. Only the T-even phages produced viable virions. We obtained complete genomes of these T-even phages, along with two contemporary T4 stocks. Performing comparative genomics, we found 12 and 16 nucleotide variations, respectively, in the genomes of T2 and T6; whereas there were ~172 nucleotide variations between T4-sublines when compared with NCBI RefSeq genome. To account for the possibility of artefacts in the NCBI RefSeq, we used the 1972 T4 stock as a reference and compared genetic and phenotypic variations between T4-sublines. Genomic analysis predicted nucleotide variations in genes associated with DNA metabolism and structural proteins. We did not however, observe any differences in growth characteristics or host range between the T4-sublines. Our study highlights the potential for genetic drift between individually maintained T-series phage stocks, yet after 48-years, this has not resulted in phenotypic alternations in these important model organisms.ImportanceT-series bacteriophages have been used throughout the world for various molecular biology researches, which were critical for establishing the fundamentals of molecular biology – from the structure of DNA to advanced gene-editing tools. These model bacteriophages help keep research data consistent and comparable between laboratories. However, we observed genetic variability when compared contemporary sublines of T4-phages to a 48-year old stock of T4. This may have effects in the comparability of results obtained using T4 phage. Here, we highlighted the genomic differences between T4 sublines and examined phenotypic differences in phage replication parameters. We observed limited genomic changes but no phenotypic variations between T4 sublines. Our research highlights the possibility of genetic drift in model bacteriophages.

scholarly journals Temporal Stability and Genetic Diversity of 48-Year-Old T-Series Phages

mSystems ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dinesh Subedi ◽  
Jeremy J. Barr
Keyword(s):  
Molecular Biology ◽  
Genetic Drift ◽  
Genetic Relatedness ◽  
Temporal Stability ◽  
Genomic Analysis ◽  
Model Organisms ◽  
Phenotypic Differences ◽  
Genomic Changes ◽  
Ncbi Refseq ◽  
Phenotypic Variations

ABSTRACT T-series phages have been model organisms for molecular biology since the 1940s. Given that these phages have been stocked, distributed, and propagated for decades across the globe, there exists the potential for genetic drift to accumulate between stocks over time. Here, we compared the temporal stability and genetic relatedness of laboratory-maintained phage stocks with a T-series collection from 1972. Only the T-even phages produced viable virions. We obtained complete genomes of these T-even phages, along with two contemporary T4 stocks. Performing comparative genomics, we found 12 and 16 nucleotide variations, respectively, in the genomes of T2 and T6, whereas there were ∼172 nucleotide variations between T4 sublines compared with the NCBI RefSeq genome. To account for the possibility of artifacts in NCBI RefSeq, we used the 1972 T4 stock as a reference and compared genetic and phenotypic variations between T4 sublines. Genomic analysis predicted nucleotide variations in genes associated with DNA metabolism and structural proteins. We did not, however, observe any differences in growth characteristics or host range between the T4 sublines. Our study highlights the potential for genetic drift between individually maintained T-series phage stocks, yet after 48 years, this has not resulted in phenotypic alterations in these important model organisms. IMPORTANCE T-series bacteriophages have been used throughout the world for various molecular biology researches, which were critical for establishing the fundamentals of molecular biology, from the structure of DNA to advanced gene-editing tools. These model bacteriophages help keep research data consistent and comparable between laboratories. However, we observed genetic variability when we compared contemporary sublines of T4 phages to a 48-year-old stock of T4. This may have effects on the comparability of results obtained using T4 phage. Here, we highlight the genomic differences between T4 sublines and examined phenotypic differences in phage replication parameters. We observed limited genomic changes but no phenotypic variations between T4 sublines. Our research highlights the possibility of genetic drift in model bacteriophages.

scholarly journals Molecular parallelism in fast-twitch muscle proteins in echolocating mammals

2018 ◽  
Vol 4 (9) ◽  
pp. eaat9660 ◽  
Author(s):  
Jun-Hoe Lee ◽  
Kevin M. Lewis ◽  
Timothy W. Moural ◽  
Bogdan Kirilenko ◽  
Barbara Borgonovo ◽  
...  
Keyword(s):  
High Frequency ◽  
Bottlenose Dolphin ◽  
Muscle Physiology ◽  
Phenotypic Differences ◽  
Genomic Changes ◽  
Calcium Storage ◽  
Fast Twitch Muscle ◽  
Little Brown Bat ◽  
Fiber Proteins ◽  
Fast Twitch

Detecting associations between genomic changes and phenotypic differences is fundamental to understanding how phenotypes evolved. By systematically screening for parallel amino acid substitutions, we detected known as well as novel cases (Strc, Tecta, and Cabp2) of parallelism between echolocating bats and toothed whales in proteins that could contribute to high-frequency hearing adaptations. Our screen also showed that echolocating mammals exhibit an unusually high number of parallel substitutions in fast-twitch muscle fiber proteins. Both echolocating bats and toothed whales produce an extremely rapid call rate when homing in on their prey, which was shown in bats to be powered by specialized superfast muscles. We show that these genes with parallel substitutions (Casq1, Atp2a1, Myh2, and Myl1) are expressed in the superfast sound-producing muscle of bats. Furthermore, we found that the calcium storage protein calsequestrin 1 of the little brown bat and the bottlenose dolphin functionally converged in its ability to form calcium-sequestering polymers at lower calcium concentrations, which may contribute to rapid calcium transients required for superfast muscle physiology. The proteins that our genomic screen detected could be involved in the convergent evolution of vocalization in echolocating mammals by potentially contributing to both rapid Ca2+ transients and increased shortening velocities in superfast muscles.

Antibiotic susceptibility profiles and frequency of resistance genes in clinical Shiga toxin-producing Escherichia coli isolates from Michigan over a 14-year period

2021 ◽  
Author(s):  
Sanjana Mukherjee ◽  
Heather M. Blankenship ◽  
Jose A. Rodrigues ◽  
Rebekah E. Mosci ◽  
James T. Rudrik ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Shiga Toxin ◽  
Antibiotic Susceptibility ◽  
Genetic Relatedness ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Mechanisms Of Resistance ◽  
Susceptibility Profiles

Background: Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen that contributes to over 250,000 infections in the US each year. Because antibiotics are not recommended for STEC infections, resistance in STEC has not been widely researched despite an increased likelihood for the transfer of resistance gene from STEC to opportunistic pathogens residing within the same microbial community. Methods: Between 2001 and 2014, 969 STEC isolates were collected from Michigan patients. Serotyping and antibiotic susceptibility profiles to clinically relevant antibiotics were determined using disc diffusion, while epidemiological data was used to identify factors associated with resistance. Whole genome sequencing was used to examine genetic relatedness and identify genetic determinants and mechanisms of resistance in the non-O157 isolates. Results: Increasing frequencies of resistance to at least one antibiotic was observed over the 14 years (p=0.01). While the non-O157 serogroups were more commonly resistant than O157 (Odds Ratio: 2.4; 95% Confidence Interval:1.43-4.05), the frequency of ampicillin resistance among O157 isolates was significantly higher in Michigan compared to the national average (p=0.03). Genomic analysis of 321 non-O157 isolates uncovered 32 distinct antibiotic resistance genes (ARGs). Although mutations in genes encoding resistance to ciprofloxacin and ampicillin were detected in four isolates, most of the horizontally acquired ARGs conferred resistance to aminoglycosides, β-lactams, sulfonamides and/or tetracycline. Conclusions: This study provides insight into the mechanisms of resistance in a large collection of clinical non-O157 STEC isolates and demonstrates that antibiotic resistance among all STEC serogroups has increased over time, prompting the need for enhanced surveillance.

scholarly journals The genomic basis of Red Queen dynamics during rapid reciprocal host–pathogen coevolution

2018 ◽  
Vol 116 (3) ◽  
pp. 923-928 ◽  
Author(s):  
Andrei Papkou ◽  
Thiago Guzella ◽  
Wentao Yang ◽  
Svenja Koepper ◽  
Barbara Pees ◽  
...  
Keyword(s):  
Genomic Analysis ◽  
Copy Number Variations ◽  
Complex Model ◽  
Time Shift ◽  
Red Queen ◽  
Genomic Changes ◽  
Selection Dynamics ◽  
Host Pathogen ◽  
Genomic Basis ◽  
Evolution With Time

Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria–phage systems or only one of the antagonists of a eukaryotic host–pathogen interaction. We add to our understanding of these important coevolutionary interactions using an experimental host–pathogen model, which includes the nematode Caenorhabditis elegans and its pathogen Bacillus thuringiensis. We combined experimental evolution with time-shift experiments, in which a focal host or pathogen is tested against a coevolved antagonist from the past, present, or future, followed by genomic analysis. We show that (i) coevolution occurs rapidly within few generations, (ii) temporal coadaptation at the phenotypic level is found in parallel across replicate populations, consistent with antagonistic frequency-dependent selection, (iii) genomic changes in the pathogen match the phenotypic pattern and include copy number variations of a toxin-encoding plasmid, and (iv) host genomic changes do not match the phenotypic pattern and likely involve selective responses at more than one locus. By exploring the dynamics of coevolution at the phenotypic and genomic level for both host and pathogen simultaneously, our findings demonstrate a more complex model of the Red Queen, consisting of distinct selective processes acting on the two antagonists during rapid and reciprocal coadaptation.

scholarly journals Fantastic beasts and how to sequence them: genomic approaches for obscure model organisms

2017 ◽  
Author(s):  
Mikhail V. Matz
Keyword(s):  
Gene Expression ◽  
Frequency Spectrum ◽  
Gene Expression Analysis ◽  
Genomic Analysis ◽  
Reference Sequence ◽  
Model Organisms ◽  
List Type ◽  
Allele Frequency Spectrum ◽  
Specific Restriction ◽  
Genomic Basis

SummaryApplication of genomic approaches to “obscure model organisms” (OMOs), meaning species with little or no genomic resources, enables increasingly sophisticated studies of genomic basis of evolution, acclimatization and adaptation in real ecological contexts. Here, I highlight sequencing solutions and data handling techniques most suited for genomic analysis of OMOs.Glossary-Allele Frequency Spectrum, AFS(same as Site Frequency Spectrum, SFS): histogram of the number of segregating variants depending on their frequency in one or more populations.-Restriction site-Associated DNA (RAD) sequencing: family of diverse genotyping methods that sequence short fragments of the genome adjacent to recognition site(s) for specific restriction endonuclease(s).-Linkage Disequilibrium (LD): in this review, correlation of genotypes at a pair of markers across individuals.-LD block: typical distance between markers in the genome across which their genotypes remain correlated.-Genome scan:profiling of genotypes along the genome looking for unusual patterns. Often used to look for signatures of natural selection or introgression.-“Denser-than-LD” genotyping: genotyping of several polymorphic markers per LD block.-Highly contiguous reference: genome or transcriptome reference sequence containing the least amount of fragmentation.-Phased data: data showing which SNP alleles belong to the same homologous chromosome copy.-Cross-tissue gene expression analysis: looking for individual-specific shifts in gene expression detectable across multiple tissues. Such shifts are predominantly genetic in nature.

scholarly journals Characterization of TGFβ-Associated Molecular Features and Drug Responses in Gastrointestinal Adenocarcinoma

2021 ◽  
Author(s):  
Qiaofeng Zhang ◽  
Furong Liu ◽  
Lu Qin ◽  
Zhibin Liao ◽  
Jia Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Genomic Analysis ◽  
Molecular Characteristics ◽  
Genomic Changes ◽  
Molecular Features ◽  
Highly Correlated ◽  
Worse Prognosis

Abstract Background: Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-β) signaling pathway is becoming a reality. However, the molecular characterization of TGF-β in GIAD requires further exploration.Results: The TGF-β­­high group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-β­­high group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-β. Further genomic analysis showed that TGF-β­­low group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed sensitive drugs or drug resistant drugs corresponding to TGF-β associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-β status in different GIAD datasets.Conclusions: Our study provided a comprehensive analysis of the molecular characteristics associated with TGF-β and provides possible therapeutic targets in GIAD.

scholarly journals Revealing genomic changes responsible for cannabinoid receptor loss in parrots: mechanism and functional effects

2022 ◽  
Author(s):  
Daniel Divin ◽  
Mercedes Gomez Samblas ◽  
Nithya Kuttiyarthu Veetil ◽  
Eleni Voukali ◽  
Zuzana Swiderska ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Inflammatory Marker ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Genomic Analysis ◽  
Sterile Inflammation ◽  
Comparative Genomic ◽  
Genomic Changes ◽  
The Brain

In vertebrates, an ancient duplication in the genes for cannabinoid receptors (CNRs) allowed the evolution of specialised endocannabinoid receptors expressed in the brain (CNR1) and the periphery (CNR2). While dominantly conserved throughout vertebrate phylogeny, our comparative genomic analysis suggests that certain taxa may have lost either the CNR1 regulator of neural processes or, more frequently, the CNR2 involved in immune regulation. Focussing on conspicuous CNR2 pseudogenization in parrots (Psittaciformes), a diversified crown lineage of cognitively-advanced birds, we highlight possible functional effects of such a loss. Parrots appear to have lost the CNR2 gene at at least two separate occasions due to chromosomal rearrangement. Using gene expression data from the brain and periphery of birds with experimentally-induced sterile inflammation, we compare CNR and inflammatory marker (interleukin 1 beta, IL1B) expression patterns in CNR2-deficient parrots (represented by the budgerigar, Melopsittacus undulatus and five other parrot species) with CNR2-intact passerines (represented by the zebra finch, Taeniopygia guttata). Though no significant changes in CNR expression were observed in either parrots or passerines during inflammation of the brain or periphery, we detected a significant up-regulation of IL1B expression in the brain after stimulation with lipopolysaccharide (LPS) only in parrots. As our analysis failed to show evidence for selection on altered CNR1 functionality in parrots, compared to other birds, CNR1 is unlikely to be involved in compensation for CNR2 loss in modulation of the neuroimmune interaction. Thus, our results provide evidence for the functional importance of CNR2 pseudogenization for regulation of neuroinflammation.

scholarly journals Gene Duplication and Gain in the Trematode Atriophallophorus Winterbourni Contributes to Adaptation to Parasitism

2021 ◽  
Author(s):  
Natalia Zajac ◽  
Stefan Zoller ◽  
Katri Seppälä ◽  
David Moi ◽  
Christophe Dessimoz ◽  
...  
Keyword(s):  
De Novo ◽  
Genomic Analysis ◽  
Enrichment Analysis ◽  
Gene Families ◽  
Comparative Genomic ◽  
Genomic Changes ◽  
Go Enrichment ◽  
Duplication Events ◽  
Parasitic Lifestyle ◽  
Host Parasite

Abstract Gene duplications and novel genes have been shown to play a major role in helminth adaptation to a parasitic lifestyle because they provide the novelty necessary for adaptation to a changing environment, such as living in multiple hosts. Here we present the de novo sequenced and annotated genome of the parasitic trematode Atriophallophorus winterbourni and its comparative genomic analysis to other major parasitic trematodes. First, we reconstructed the species phylogeny, and dated the split of A. winterbourni from the Opisthorchiata suborder to approximately 237.4 MYA (± 120.4 MY). We then addressed the question of which expanded gene families and gained genes are potentially involved in adaptation to parasitism. To do this, we used Hierarchical Orthologous Groups to reconstruct three ancestral genomes on the phylogeny leading to A. winterbourni and performed a GO enrichment analysis of the gene composition of each ancestral genome, allowing us to characterize the subsequent genomic changes. Out of the 11,499 genes in the A. winterbourni genome, as much as 24% have arisen through duplication events since the speciation of A. winterbourni from the Opisthorchiata, and as much as 31.9% appear to be novel, i.e. newly acquired. We found 13 gene families in A. winterbourni to have had more than 10 genes arising through these recent duplications; all of which have functions potentially relating to host behavioural manipulation, host tissue penetration, and hiding from host immunity through antigen presentation. We identified several families with genes evolving under positive selection. Our results provide a valuable resource for future studies on the genomic basis of adaptation to parasitism and point to specific candidate genes putatively involved in antagonistic host-parasite adaptation.

scholarly journals Structured growth and genetic drift raise relatedness in the social amoeba Dictyostelium discoideum

2012 ◽  
Vol 8 (5) ◽  
pp. 794-797 ◽  
Author(s):  
Neil J. Buttery ◽  
Chandra N. Jack ◽  
Boahemaa Adu-Oppong ◽  
Kate T. Snyder ◽  
Christopher R. L. Thompson ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Genetic Drift ◽  
Genetic Relatedness ◽  
Kin Recognition ◽  
Single Cells ◽  
Small Population ◽  
Recognition Mechanism ◽  
Short Supply ◽  
Social Amoeba ◽  
The Social

One condition for the evolution of altruism is genetic relatedness between altruist and beneficiary, often achieved through active kin recognition. Here, we investigate the power of a passive process resulting from genetic drift during population growth in the social amoeba Dictyostelium discoideum . We put labelled and unlabelled cells of the same clone in the centre of a plate, and allowed them to proliferate outward. Zones formed by genetic drift owing to the small population of actively growing cells at the colony edge. We also found that single cells could form zones of high relatedness. Relatedness increased at a significantly higher rate when food was in short supply. This study shows that relatedness can be significantly elevated before the social stage without a small founding population size or recognition mechanism.

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