Biology subjects

Walker, J.

Publications and source records attributed to Walker, J..

45 records · Page 3Linked to original sources

bioRxiv2020

Development of Wheat-Aegilops caudata Introgression Lines and Their Characterisation Using Genome-Specific KASP Markers

Aegilops caudata L. [syn. Ae. markgrafii (Greuter) Hammer], a diploid wild relative of wheat (2n = 2x = 14, CC), is an important source for new genetic variation for wheat improvement due to a variety of disease resistance factors along with tolerance for various abiotic stresses. Its practical utilisation in wheat improvement can be facilitated through the generation of genome-wide introgressions leading to a variety of different wheat-Ae. caudata recombinant lines. In this study, we report the generation of nine such wheat-Ae. caudata recombinant lines which were characterized using wheat genome-specific KASP (Kompetitive Allele Specific PCR) markers and multi-colour genomic in situ hybridization (mcGISH). Of these, six lines have stable homozygous introgressions from Ae. caudata and will be used for future trait analysis. Through a combination of molecular and cytological analysis of all the recombinant lines, we were able to physically map 182 KASP markers onto the seven Ae. caudata chromosomes, of which 155 were polymorphic specifically with only one wheat subgenome. Comparative analysis of the physical positions of these markers in the Ae. caudata and wheat genomes confirmed that the former had chromosomal rearrangements with respect to wheat, as previously reported. These wheat-Ae. caudata recombinant lines and KASP markers provide a useful genetic resource for wheat improvement with the latter having a wider impact as a tool for detection of introgressions from other Aegilops species into wheat.

genetics↗

bioRxiv2020

Emergence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing

ObjectivesTo characterise the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. MethodsLinezolid-resistant E. faecalis were identified in three Scottish Health Boards and confirmed to carry the optrA gene at the national reference laboratory. WGS was performed with short read (Illumina MiSeq) and long read (Oxford Nanopore MinION) technologies to generate complete genome assemblies. Illumina reads for 94 E. faecalis bloodstream isolates were used to place the optrA-positive isolates in a larger UK phylogeny. ResultsSix optrA-positive linezolid-resistant E. faecalis were isolated from urogenital samples in three Scottish Health Boards (2014-2017). No epidemiological links were identified between the patients, four were community-based, and only one had recent linezolid exposure. Reference-based mapping confirmed the isolates were genetically distinct (>13,900 core SNPs). optrA was located on a plasmid in each isolate and these plasmids showed limited nucleotide similarity. There was variable presence of transposable elements surrounding optrA, (including IS1216, IS3, and Tn3) and not always as a recognisable gene cassette. OptrA amino acid sequences were also divergent, resulting in four protein variants differing in 1-20 residues. One isolate belonged to ST16 and clustered with three other isolates in the UK collection (76-182 SNPs), otherwise the optrA-positive isolates were genetically distinct from the bloodstream isolates (>6,000 SNPs). ConclusionsWe report multiple variants of the linezolid resistance gene optrA in diverse E. faecalis strain and plasmid backgrounds, suggesting multiple introductions of the gene into the E. faecalis population and selection driving recent emergence.

microbiology↗

bioRxiv2020

Multi-proxy evidence for the impact of the Storegga Slide Tsunami on the early Holocene landscapes of the southern North Sea

Doggerland was a land mass occupying an area currently covered by the North Sea until marine inundation took place during the mid-Holocene, ultimately separating the British land mass from the rest of Europe. The Storegga Slide, which triggered a tsunami reflected in sediment deposits in the Northern North Sea, North East coastlines of the British Isles and across the North Atlantic, was a major event during this transgressive phase. The spatial extent of the Storegga tsunami however remains unconfirmed because to date no direct evidence for the event has been recovered from the southern North Sea. We present evidence that Storegga associated deposits occur in the southern North Sea. Palaeo-river systems have been identified using seismic survey in the southwestern North Sea and sedimentary cores extracted to track the Mid Holocene inundation. At the head of one palaeo-river system near the Outer Dowsing Deep, the Southern River, we observed an abrupt and catastrophic inundation stratum. Based on lithostratigraphic, macro and microfossils and sedimentary ancient DNA (sedaDNA) evidence, supported by optical stimulation luminescence (OSL) and radiocarbon dating, we conclude these deposits were a result of the Storegga event. Seismic identification of this stratum to adjacent cores indicated diminished traces of the tsunami, largely removed by subsequent erosional processes. Our results demonstrate the catastrophic impact of Storegga within this area of the Southern North Sea, but indicate that these effects were temporary and likely localized and mitigated by the dense woodland and topography of the area. We conclude clear physical remnants of the wave are likely to be restricted to inland basins and incised river valley systems.

paleontology↗

bioRxiv2018

pVACtools: a computational toolkit to select and visualize cancer neoantigens

The elucidation of neoantigens is a critical step in predicting response to checkpoint blockade therapy and design of personalized cancer vaccines. We have developed an in silico sequence analysis method - pVACtools, to facilitate comprehensive neoantigen characterization. This modular workflow consists of tools for neoantigen prediction from somatic alterations (pVACseq and pVACfuse), prioritization and selection using a graphical web-based interface (pVACviz), and determining the optimal order of neoantigen candidates in a DNA vector-based vaccine(pVACvector).

bioinformatics↗

bioRxiv2018

A mechanistic hydro-epidemiological model of liver fluke risk

The majority of existing models for predicting disease risk in response to climate change are empirical. These models exploit correlations between historical data, rather than explicitly describing relationships between cause and response variables. Therefore, they are unsuitable for capturing impacts beyond historically observed variability and cannot be employed to assess interventions. In this study, we integrate environmental and epidemiological processes into a new mechanistic model, taking the widespread parasitic disease of fasciolosis as an example. The model simulates environmental suitability for disease transmission, explicitly linking the parasite life-cycle to key weather-water-environment conditions. First, using epidemiological data, we show that the model can reproduce observed infection levels in time and space over two case studies in the UK. Second, to overcome data limitations, we propose a calibration approach based on Monte Carlo sampling and expert opinion, which allows constraint of the model in a process-based way, including a quantification of uncertainty. Finally, comparison with information from the literature and a widely-used empirical risk index shows that the simulated disease dynamics agree with what has been traditionally observed, and that the new model gives better insight into the time-space patterns of infection, which will be valuable for decision support.

epidemiology↗

bioRxiv2018

Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M

The balance between stem cell quiescence and proliferation in skeletal muscle is tightly controlled, but perturbed in a variety of disease states. Despite progress in identifying activators of stem cell proliferation, the niche factor(s) responsible for quiescence induction remain unclear. Here we report an in vivo imaging-based screen which identifies Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent inducer of muscle stem cell (MuSC, satellite cell) quiescence. OSM is produced by muscle fibers, induces reversible MuSC cell cycle exit, and maintains stem cell regenerative capacity as judged by serial transplantation. Conditional OSM receptor deletion in satellite cells leads to stem cell depletion and impaired regeneration following injury. These results identify Oncostatin M as a secreted niche factor responsible for quiescence induction, and for the first time establish a direct connection between induction of quiescence, stemness, and transplantation potential in solid organ stem cells.

cell biology↗

bioRxiv2018

De novo origin of multicellularity in response to predation

The transition from unicellular to multicellular life was one of a few major events in the history of life that created new opportunities for more complex biological systems to evolve. Predation is hypothesized as one selective pressure that may have driven the evolution of multicellularity. Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations. Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates. Survival assays show that evolved multicellular traits provide effective protection against predation. These results support the hypothesis that selection imposed by predators may have played a role in some origins of multicellularity.

evolutionary biology↗

bioRxiv2017

Sexual lineage specific DNA methylation regulates Arabidopsis meiosis

DNA methylation controls eukaryotic gene expression and is extensively reprogrammed to regulate animal development. However, whether developmental methylation reprogramming during the sporophytic life cycle of flowering plants regulates genes is presently unknown. Here we report a distinctive, gene-targeted RNA-directed DNA methylation (RdDM) activity in the Arabidopsis thaliana male sexual lineage that regulates gene expression in meiocytes. Loss of sexual lineage-specific RdDM causes mis-splicing of the MPS1/PRD2 gene, thereby disrupting meiosis. Our results establish a regulatory paradigm in which de novo methylation creates a cell-lineage-specific epigenetic signature that controls gene expression and contributes to cellular function in flowering plants.

plant biology↗

bioRxiv2017

Improved Transcriptome Sampling Pinpoints 26 Paleopolyploidy Events In Caryophyllales, Including Two Paleo-Allopolyploidy Events

O_LIStudies of the macroevolutionary legacy of paleopolyploidy are limited by an incomplete sampling of these events across the tree of life. To better locate and understand these events, we need comprehensive taxonomic sampling as well as homology inference methods that accurately reconstruct the frequency and location of gene duplications.\nC_LIO_LIWe assembled a dataset of transcriptomes and genomes from 169 species in Caryophyllales, of which 43 were newly generated for this study, representing one of the densest sampled genomic-scale datasets yet available. We carried out phylogenomic analyses using a modified phylome strategy to reconstruct the species tree. We mapped phylogenetic distribution of paleopolyploidy events by both tree-based and distance-based methods, and explicitly tested scenarios for paleo-allopolyploidy.\nC_LIO_LIWe identified twenty-six paleopolyploidy events distributed throughout Caryophyllales, and using novel techniques inferred two to be paleo-allopolyploidy.\nC_LIO_LIThrough dense phylogenomic sampling, we show the propensity of paleo-polyploidy in the clade Caryophyllales. We also provide the first method for utilizing transcriptome data to detect paleo-allopolyploidy, which is important as it may have different macro-evolutionary implications compared to paleo-autopolyploidy.\nC_LI

evolutionary biology↗