Biology subjects

Davison, J.

Publications and source records attributed to Davison, J..

4 recordsLinked to original sources

bioRxiv2026

Holobiomes in succession: post-glacial microbial communities are structured by hosts, time and habitat heterogeneity

O_LIGlacier forefields in the high-desert region of Ladakh (northwestern Himalaya) are colonized by a variety of interdependent organisms, including lichens, prokaryotes, fungi, mosses, and vascular plants, along a successional gradient. Together with bulk soil, these hosts and their associated microorganisms form a broader microbial metacommunity (holobiome) whose structure, interactions and functions remain poorly underexplored in one of the Earths most extreme and climate-sensitive environments. C_LIO_LIUsing a multidisciplinary approach combining glacial chronosequence transects, GIS-derived topographic variables, soil properties, and plot cover measurements, we assessed the abiotic and biotic factors influencing bacterial and fungal communities sequenced from different hosts and bulk soil (hereafter sources). Microbial composition was primarily shaped by source identity, though certain sources, such as biological soil crusts (BSCs), mosses, and plant rhizospheres, also showed relationships with moraine age in either bacterial or fungal communities. C_LIO_LIBacterial and fungal community congruence was tested using Procrustes analyses, revealing that mosses maintained tightly coupled inter-kingdom relationships throughout the glacier forefields. However, the degree of congruence in plant rhizospheres and bulk soils was influenced by topographic variation and moraine age, respectively. C_LIO_LICo-occurrence network analyses revealed that early successional microbial communities were assembled more stochastically, with bacteria being more interconnected than fungi. In contrast, late successional stages were more compartmentalized, being more structurally stabile, likely driven by increased plant cover and functional redundancy among microbial taxa. C_LIO_LIKeystone bacterial and fungal taxa were identified in plant rhizospheres and bulk soil using a dual-criteria approach related to inter-kingdom congruence and network node eigenvalues. Furthermore, some of these taxa were associated with environmental factors, suggesting topographic heterogeneity and successional age can promote or deter the influence of keystone taxa. C_LIO_LISynthesis: This study reveals the impact of both macroorganism colonization (i.e. plants, mosses, and lichens) and microcommunity establishment (BSCs and bulk soil), as abiotic and biotic sources, on microbial metacommunity assembly in glacier forefields. By adopting a broader approach across different spatial scales, we demonstrate that while plant colonization plays a central role in shaping microbial metacommunities, its effects are modulated by topographic variation along the chronosequence. C_LI

microbiology↗

bioRxiv2023

The incidence of movement disorders increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.

Argininosuccinate lyase is integral to the urea cycle detoxifying neurotoxic ammonia and the nitric oxide biosynthesis cycle. Inherited argininosuccinate lyase deficiency causes argininosuccinic aciduria (ASA), a rare disease with hyperammonaemia and nitric oxide deficiency. Patients present with developmental delay, epilepsy and movement disorders, associated with nitric oxide-mediated downregulation of central catecholamine biosynthesis. A neurodegenerative phenotype has been proposed in ASA. To better characterise this neurodegenerative phenotype in ASA, we conducted a retrospective study in six paediatric and adult metabolic centres in the UK in 2022. We identified 60 patients and specifically looked for movement disorders-related symptoms: movement disorders such as ataxia, tremor and dystonia, hypotonia and abnormal behaviour. We analysed neuroimaging with diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) in an ASA patient with movement disorders. We assessed conventional and DTI MRI alongside single photon emission computer tomography (SPECT) with dopamine analogue radionuclide 123I-ioflupane, in Asl-deficient mice treated by hASL mRNA with normalised ureagenesis. Movement disorders in ASA appears in the 2nd and 3rd decades of life, becoming more prevalent with ageing and independent from the age of onset of hyperammonaemia. Neuroimaging can show abnormal DTI features affecting both grey and white matter, preferentially basal ganglia. ASA mouse model with normalised ureagenesis did not recapitulate these DTI findings and showed normal 123I-ioflupane SPECT and cerebral dopamine metabolomics. Altogether these findings support the pathophysiology of a late-onset movement disorders with functional central catecholamine dysregulation but without or limited neurodegeneration of dopaminergic neurons, making these symptoms amenable to targeted therapy. SynopsisMovement disorders-related symptoms in ASA appear in the 2nd and 3rd decades of life, becoming more prevalent with age and shows abnormal neuroimaging features of basal ganglia in ASA patients, not recapitulated in ASA mice.

genetics↗

bioRxiv2021

Origins of cancer genome complexity revealed by haplotype-resolved genomic analysis of evolution of Barretts esophagus to esophageal adenocarcinoma

The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations but how these alterations arise is poorly understood. Here we performed haplotype-specific analysis of chromosomal copy-number evolution in the progression of Barretts esophagus (BE) to esophageal adenocarcinoma (EAC) on multiregional whole-genome sequencing data of BE with dysplasia and microscopic EAC foci. We identified distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss. While abnormal mitosis, including whole-genome duplication, underlies chromosomal copy-number changes, segmental alterations display signatures of successive breakage-fusion-bridge cycles and chromothripsis of unstable dicentric chromosomes. Our analysis elucidates how multigenerational chromosomal instability generates copy-number variation in BE cells, precipitates complex alterations including DNA amplifications, and promotes their independent clonal expansion and transformation. In particular, we suggest sloping copy-number variation as a signature of ongoing chromosomal instability that precedes copy-number complexity. These findings suggest copy-number heterogeneity in advanced cancers originates from chromosomal instability in precancerous cells and such instability may be identified from the presence of sloping copy-number variation in bulk sequencing data.

genomics↗

bioRxiv2019

The structure of bacteriophage T5 injection stop signal.

Escherichia coli bacteriophage T5 differs from most phages in that it injects its genome in two steps: First Step Transfer, FST, corresponding to leftmost 7.9% of the genome and Second Step Transfer, SST, corresponding to the remainder of the genome. Expression of genes A1 and A2 is required for SST. DNA injection stops at a site known as the injection stop signal (iss) which is a cis acting site located in the large untranslated region of the Left Terminal Repeat (LTR). The iss region is extremely complicated with many repeats, inverted repeats and palindromes. This report compares the iss regions of 25 T5-like phages and shows that all have a common conserved structure including a series of 8 DnaA boxes arranged in a highly specific manner; reminiscent of the origin of replication (oriC) of E. coli. DnaA protein, which binds to DnaA boxes, is a mostly membrane bound. A new, radically different, mechanism of T5 2-step injection is proposed whereby injecting T5 DNA stops at the plasma membrane due to the binding of the iss DnaA boxes to membrane-bound DnaA protein. Injection of the SST continues later via the combined action of the A1 and A2 proteins which cleave the FST DNA at a site upstream (right) of the iss region, thereby liberating it. They also cleave the incoming SST DNA at the same site on the RTR thus facilitating circularisation of one complete genome via the cohesive ends. Circle formation protects the T5 DNA from the degradative action of the RecBCD nuclease and eventually leads to rolling circle DNA replication.

microbiology↗