Biology subjects

Hall, R. J.

Publications and source records attributed to Hall, R. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Age-dependent effects of infection on survival of a wild rodent reservoir host

Due to long co-evolutionary histories, many zoonotic pathogens are thought to exert little or no negative effects on their wildlife reservoir hosts. However, there remains a lack of rigorous investigations in natural settings. We conducted a 3-year factorial field experiment to investigate how survival of the Puumala hantavirus (PUUV) reservoir, the bank vole, is impacted by PUUV infection, nematode infections, and food availability. We hypothesized that PUUV would not impact survival, but that coinfection with nematodes would negatively impact survival, and that increased food availability would mitigate the negative effects of coinfection. Surprisingly, we demonstrated that PUUV infected voles had substantially reduced survival when compared to uninfected voles, and this strong negative effect manifested in young voles. Nematode removal increased survival of young voles and food supplementation interacted with movement rather than survival. Our results provide empirical evidence in a natural system for infection reducing survival of its reservoir host.

ecology↗

bioRxiv2026

A remarkable case of conserved domain swapping in the COMMD family of proteins

The eukaryotic COMMD family of proteins are core subunits of the Commander protein complex, with a central role in endosomal membrane trafficking and signalling. Previous crystal and cryoEM structures show that COMMD and COMMD-like proteins form homo-oligomeric and hetero-decameric assemblies with a central ring structure formed by their small C-terminal COMM domains. Their -helical N-terminal (HN) domains decorate each side of these rings, and in the eukaryotic Commander complex engage the coiled-coil proteins CCDC22 and CCDC93. Here, we have determined new crystal structures of the isolated HN domains of human Commd4, Commd9 and Commd10, and find that all three proteins form domain swapped structures with a remarkably consistent topology. This occurs via a conformational change in a hinge-loop between helices 2 and 3, leading to exchange of helices 3 to 6 between protomers. The hinge-loops of Commd9 and Commd10 possess several serine and threonine residues that can be phosphorylated, and we find that specific phospho-mimicking mutations in Commd10 can promote or inhibit domain swapping. Whether the unique COMMD HN domains play any roles beyond assembly with CCDC proteins is unclear, but this work suggests a common conformational switch exists with a potential to regulate their function.

biochemistry↗

bioRxiv2026

Food Supplementation Reduces Nematode Super-Shedding in a Wild Mammal

Anthropogenic changes to the environment, including altered food resource availability, influence host physiology, behaviour, and population dynamics, which can have strong downstream consequences on wildlife disease dynamics. Additionally, some individuals within a population contribute disproportionately to infection as super-shedders of infection, but the extent to which food availability alters the likelihood of super-shedding and overall parasite infection patterns is poorly understood. We conducted a three-year field experiment in southern Finland to investigate how food supplementation and parasite removal affect nematode infection measures and the relationship between nematode infection and fitness of wild bank voles (Clethrionomys glareolus). Using a factorial design across 12 populations, we manipulated food availability and administered anthelmintic treatments to assess effects on nematode infection status, intensity, and two measures of super-shedding (abundance super-shedding, intensity super-shedding). We also examined parasite impacts on host fitness, including apparent survival probability and reproductive status. Food supplementation did not affect likelihood of infection, intensity or intensity super-shedding, but did reduce the likelihood of abundance super-shedding, suggesting an effect of food availability on infection heterogeneity. We also identified an interaction between nematode infection status and host age on fitness. Notably, infected younger individuals had reduced survival and reproduction, but infected older individuals had greater survival and reproduction compared to their uninfected counterparts. Our study provides novel empirical evidence on how anthropogenic changes in food availability can influence parasite transmission dynamics and the fitness consequences of these sub-lethal parasites in a wildlife system.

ecology↗

bioRxiv2025

Genomic rearrangement of the capsule operon in a phylogenetically distinct cluster of the multi-drug resistant Escherichia coli lineage ST131

Escherichia coli ST131 is a dominant cause of multi-drug resistant extra-intestinal infections in humans. The lineage has a three-clade phylogenetic structure of which clade C has gained resistance to multiple classes of antibiotics and is globally disseminated. As well as antimicrobial resistance, a number of virulence factors contribute to the success of ST131 clade C, including the production of capsule. Previous work on a limited number of strains has shown that the capsule operon in ST131 is highly variable. In this study we analysed the capsule genetics of E. coli ST131 by interrogating 3,033 genomes. Our data show a clonal distribution of capsule types and identify a monophyletic group of ST131 clade C strains which are characterised by an atypical capsule operon with highly divergent alleles of the key kpsM and kpsT genes. Our analysis suggests there is ongoing evolution within clade C of ST131 which looks to be driven not by continuing evolution of antimicrobial resistance, but by host-pathogen interactions.

microbiology↗

bioRxiv2024

Glucose alters the evolutionary response to gentamicin in uropathogenic Escherichia coli

Urinary tract infections (UTI) are a major health and economic concern. Uropathogenic Escherichia coli (UPEC) are the leading cause of UTI, and antibiotic resistant UPEC are increasingly common. The microenvironment of the urinary tract is metabolically distinct, and there is growing interest in understanding the extent to which metabolism may influence UPEC infection and response to antibiotics, and how this varies between individuals. Diabetes, characterised in part by glycosuria, is a known risk factor for UTI and is associated with more severe infections. The role that glucose plays in driving UPEC evolution is unclear. Here, we found that a pathologically-relevant glucose concentration reduced the efficacy of the antibiotic gentamicin against a UPEC strain. Through experimental evolution, we identified mutations in the RNA polymerase sigma factor rpoS associated with long-term glucose exposure. We found that the presence of gentamicin resulted in mutations in genes including trkH, encoding a potassium ion uptake system and linked previously to aminoglycoside resistance, and in the autotransporter hyxB. Strikingly, these mutations were not present in populations exposed to a combination of both glucose and gentamicin. Together, this suggests that whilst glucose may reduce growth inhibition by gentamicin, it may also influence mutation acquisition, providing new avenues for understanding the evolution and treatment of UPEC-mediated UTI in high-risk individuals.

microbiology↗

bioRxiv2024

Mean daily temperatures can predict the thermal limits of malaria transmission better than rate summation

Temperature shapes the distribution, seasonality, and magnitude of mosquito-borne disease outbreaks. Mechanistic models predicting transmission often use mosquito and pathogen thermal responses from constant temperature experiments. However, mosquitoes live in fluctuating environments. Rate summation (nonlinear averaging) is a common approach to infer performance in fluctuating environments, but its accuracy is rarely validated. We measured three mosquito traits that impact transmission (bite rate, survival, fecundity) in a malaria mosquito (Anopheles stephensi) across temperature gradients with three diurnal temperature ranges (0, 9 and 12{degrees}C). We compared thermal suitability models with temperature-trait relationships observed under constant temperatures, fluctuating temperatures, and those predicted by rate summation. We mapped results across An. stephenesis native Asian and invasive African ranges. We found: 1) daily temperature fluctuation significantly altered trait thermal responses; 2) rate summation partially captured decreases in performance near thermal optima, but also incorrectly predicted increases near thermal limits; and 3) while thermal suitability characterized across constant temperatures did not perfectly capture suitability in fluctuating environments, it was more accurate for estimating and mapping thermal limits than predictions from rate summation. Our study provides insight into methods for predicting mosquito-borne disease risk and emphasizes the need to improve understanding of organismal performance under fluctuating conditions.

ecology↗

bioRxiv2024

Perceived and observed biases within scientific communities: a case study in movement ecology

Who conducts biological research, where, and how the results are disseminated varies among geographies and identities. Identifying and documenting these forms of bias by research communities is a critical first step towards addressing them. We documented perceived and observed biases in movement ecology. Movement ecology is a rapidly expanding sub-discipline of biology, which is strongly underpinned by fieldwork and technology use. First, we surveyed attendees of an international conference, and discussed the results at the conference (comparing uninformed vs informed perceived bias). Although most researchers identified as bias-aware, only a subset of biases were discussed in conversation. Next, by considering author affiliations from publications in the journal Movement Ecology, we found among-country discrepancies between the country of the authors affiliation and study site location related to national economics. At the within-country scale, we found that race-gender identities of postgraduate biology researchers in the USA differed from national demographics. We discuss the role of potential specific causes for the emergence of bias in the sub-discipline, e.g. parachute-science or accessibility to fieldwork. Undertaking data-driven analysis of bias within research sub-disciplines can help identify specific barriers and first steps towards the inclusion of a greater diversity of participants in the scientific process.

ecology↗

bioRxiv2024

Longitudinal genomic surveillance of a UK intensive care unit shows a lack of patient colonisation by multi-drug resistant Gram-negative pathogens

Vulnerable patients in an intensive care unit (ICU) setting are at high risk of infection from bacteria including gut-colonising Escherichia coli and Klebsiella species. Complex ICU procedures often depend on successful antimicrobial treatment, underscoring the importance of understanding the extent of patient colonisation by multi-drug resistant organisms (MDRO) in large UK ICUs. Previous work on ICUs globally uncovered high rates of colonisation by and transmission of MDRO, but the situation in UK ICUs is less understood. Here, we investigated the diversity and antibiotic resistance gene (ARG) carriage of bacteria present in one of the largest UK ICUs at the Queen Elizabeth Hospital Birmingham (QEHB), focussing primarily on E. coli as both a widespread commensal and a globally disseminated multidrug resistant pathogen. Samples were taken during highly restrictive COVID-19 control measures from May - December 2021. Whole-genome and metagenomic sequencing were used to detect and report strain level colonisation of patients, focussing on E. coli sequence types (STs), their colonisation dynamics, and antimicrobial resistance (AMR) gene carriage. We found a lack of multidrug resistance (MDR) in the QEHB. Only one carbapenemase-producing organism was isolated, a Citrobacter carrying blaKPC-2. There was no evidence supporting the spread of this strain, and there was little evidence overall of nosocomial acquisition or circulation of colonising E. coli. Whilst 22 different E. coli STs were identified, only one strain of the pandemic ST131 lineage was isolated. This ST131 strain was non-MDR and was found to be a clade A strain, associated with low levels of antibiotic resistance. Overall, the QEHB ICU had very low levels of pandemic or MDR strains, a result which may be influenced in part by the strict COVID-19 control measures in place at the time. Employing some of these infection prevention and control measures where reasonable in all ICUs might therefore assist in maintaining low levels of nosocomial MDR. Impact statementThis study contributes to current literature on the potential routes for AMR spread in a healthcare setting. This study used whole genome sequencing (WGS) to investigate at strain-level bacterial species (including E. coli) colonising the gut of long-stay patients in the ICU. WGS in combination with patient ward movement and prescribing information was used to assess any links or driving factors in strain acquisition and AMR spread in the ICU. Our study gives an insight at a point in time where infection and prevention control restrictions and awareness were high due to the COVID-19 pandemic, combined with local and national travel restrictions and isolation criteria. Consequently, it provides a novel longitudinal dataset that gives a picture of colonising E. coli in a sheltered ICU patient population. Trends seen in this E. coli population are likely linked to the United Kingdom in 2021 rather than the global picture that may have been seen prior to the COVID-19 pandemic. Data summaryAll supporting data, code and protocols have been provided within the article or through supplementary data files. All genomic and metagenomic data are available from NCBI under BioProject accession PRJNA1136496. All relevant metadata is provided in supplementary data files.

microbiology↗

bioRxiv2024

Ecological factors alter how spatial overlap predicts viral infection dynamics in wild rodent populations

Spatial overlap between animals in wildlife populations can have important implications for pathogen transmission. Ecological factors and animal demographic traits can influence animal space use and spatial overlap, but it is unclear how these interactions drive pathogen transmission. We experimentally manipulated wild bank vole populations via resource supplementation and anthelmintic treatment. Using network analysis, we investigated the relationship between spatial overlap and infection likelihood of an endemic zoonotic hantavirus, including how vole sex and reproductive status interact with spatial behaviour to affect infection likelihood. Spatial overlap in a previous month drove the likelihood of current hantavirus infection, and food supplementation and anthelmintic treatment altered the effects of spatial overlap on infection likelihood. Vole sex and reproductive status were important factors determining whether spatial overlap increased or decreased the likelihood of hantavirus infection and interacted with resource supplementation and anthelmintic treatment, generating different infection dynamics in each treatment. Our research provides rare empirical evidence linking previous spatial overlap to current infection status in wildlife populations, with implications for understanding disease dynamics and persistence as well as developing effective management efforts. We further highlight the importance of incorporating variation in ecological factors and host demography when studying pathogen transmission in wildlife systems.

ecology↗

bioRxiv2023

Multidrug resistance plasmids commonly reprogramme expression of metabolic genes in Escherichia coli

Multidrug resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance genes between lineages is driving the rising rates of hard to treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and whilst a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from >650 to <20 chromosomal genes being differentially expressed. However, neither the scale of regulatory disruption nor the plasmid size correlated with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes varied among plasmids, although expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli. ImportanceThe increase of infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests possible targets for reducing plasmid transfer.

microbiology↗

bioRxiv2023

Non-antibiotic pharmaceuticals exhibit toxicity against Escherichia coli at environmentallyrelevant concentrations with no evolution of cross-resistance to antibiotics

Antimicrobial resistance can arise in the natural environment via prolonged exposure to the effluent surrounding manufacturing facilities. These facilities also produce non-antibiotic pharmaceuticals, and the effect of these on the surrounding microbial communities is less clear; whether they have inherent toxicity, or whether long-term exposure might select for cross-resistance to antibiotics. To this end, we screened four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, met formin) and titanium dioxide for toxicity against Escherichia coli K-12 MG1655 and conducted a 30 day selection experiment to assess the effect of long-term exposure. All compounds reduced the maximum optical density reached by E. coli at a range of concentrations including one of environmental relevance, with transcriptome analysis identifying upregulated genes related to stress response and multidrug efflux in response ibuprofen treatment. The non-antibiotic pharmaceuticals did not select for significant genetic changes following a 30 day exposure, and no evidence of selection for cross-resistance to antibiotics was observed for population evolved in the presence of ibuprofen in spite of the differential gene expression after exposure to this compound. This work suggests that these non-antibiotic pharmaceuticals, at environmental concentrations, do not select for cross-resistance to antibiotics in E. coli.

microbiology↗

bioRxiv2023

Growth in a biofilm promotes conjugation of a blaNDM-1-bearing plasmid between Klebsiella pneumoniae strains

Antimicrobial resistance (AMR) is a growing problem, especially in Gram-negative Enterobacteriaceae such as Klebsiella pneumoniae. Horizontal transfer of conjugative plasmids contributes to AMR gene dissemination. Bacteria such as K. pneumoniae commonly exist in biofilms, yet most studies focus on planktonic cultures. Here we studied the transfer of a multidrug resistance plasmid in planktonic and biofilm populations of K. pneumoniae. We determined plasmid transfer from a clinical isolate, CPE16, which carried four plasmids, including the 119-kbp blaNDM-1-bearing F-type plasmid pCPE16_3, in planktonic and biofilm conditions. We found that transfer frequency of pCPE16_3 in a biofilm was orders-of-magnitude higher than between planktonic cells. In 5/7 sequenced transconjugants multiple plasmids had transferred. Plasmid acquisition had no detectable growth impact on transconjugants. Gene expression of the recipient and a transconjugant was investigated by RNA-sequencing in three lifestyles: planktonic exponential growth, planktonic stationary phase, and biofilm. We found that lifestyle had a substantial impact on chromosomal gene expression, and plasmid carriage affected chromosomal gene expression most in stationary planktonic and biofilm lifestyles. Furthermore, expression of plasmid genes was lifestyle-dependent, with unique signatures across the three conditions. Our study shows that growth in biofilm greatly increased the risk of conjugative transfer of a carbapenem resistance plasmid in K. pneumoniae without fitness costs and minimal transcriptional rearrangements, thus highlighting the importance of biofilms in the spread of AMR in this opportunistic pathogen. ImportanceCarbapenem-resistant K. pneumoniae is particularly problematic in hospital settings. Carbapenem resistance genes can transfer between bacteria via plasmid conjugation. Alongside drug resistance, K. pneumoniae can form biofilms on hospital surfaces, at infection sites and on implanted devices. Biofilms are naturally protected and can be inherently more tolerant to antimicrobials than their free-floating counterparts. There have been indications that plasmid transfer may be more likely in biofilm populations, thus creating a conjugation hotspot. However, there is no clear consensus on the effect of the biofilm lifestyle on plasmid transfer. Therefore, we aimed to explore the relationship between plasmid transfer and biofilms, and the impact of plasmid acquisition on the host bacterial cell. Our data show resistance plasmid transfer is greatly increased in a biofilm versus planktonic growth, which may be a significant contributing factor to the rapid dissemination of resistance plasmids in K. pneumoniae.

microbiology↗

bioRxiv2022

Effects of Food Addition and Helminth Removal on Space Use and Spatial Overlap in Wild Rodent Populations

1. Animal space use and spatial overlap can have important consequences for population-level processes such as social interactions and pathogen transmission. Identifying how environmental variability and inter-individual variation affect spatial patterns and in turn influence interactions in animal populations is a priority for the study of animal behavior and disease ecology. Environmental food availability and macroparasite infection are common drivers of variation, but there are few experimental studies investigating how they affect spatial patterns of wildlife. 2. Bank voles (Clethrionomys glareolus) are a tractable study system to investigate spatial patterns of wildlife and are amenable to experimental manipulations. We conducted a replicated, factorial field experiment in which we provided supplementary food and removed helminths in vole populations in natural forest habitat and monitored vole space use and spatial overlap using capture-mark-recapture methods. 3. Using network analysis, we quantified vole space use and spatial overlap. We compared the effects of food supplementation and helminth removal and investigated the impact of season, sex, and reproductive status on space use and spatial overlap. 4. We found that food supplementation decreased vole space use while helminth removal increased space use. Space use also varied by sex, reproductive status, and season. Spatial overlap was similar between treatments despite up to three-fold differences in population size. 5. By quantifying the spatial effects of food availability and macroparasite infection on wildlife populations, we demonstrate the potential for space use and population density to trade off and maintain consistent spatial overlap in wildlife populations. This has important implications for spatial processes in wildlife including pathogen transmission.

ecology↗

bioRxiv2022

Pangenome evolution in Escherichia coli is sequence type, not phylogroup, specific

The Escherichia coli species contains a diverse set of sequence types and there remain important questions regarding differences in genetic content within this population that need to be addressed. Pangenomes are useful vehicles for studying gene content within sequence types. Here, we analyse 21 E. coli sequence type pangenomes using comparative pangenomics to identify variance in both pangenome structure and content. We present functional breakdowns of sequence type core genomes and identify sequence types that are enriched in metabolism, transcription and cell membrane biogenesis genes. We also uncover metabolism genes that have variable core classification depending on which allele is present. Our comparative pangenomics approach allows for detailed exploration of sequence type pangenomes within the context of the species. We show that pangenome evolution is independent of phylogenetic signal at the phylogroup level, which may be a consequence of distinct sequence type-specific driving factors relating to ecology and pathogenic phenotype. Data SummarySupporting data and code have been provided within the article or through Supplementary Data files available at https://doi.org/10.6084/m9.figshare.19793758. Custom Python scripts used to perform analyses are available at github.com/lillycummins/InterPangenome unless otherwise stated in the text.

microbiology↗

bioRxiv2021

Proteomic identification and structural basis for the interaction between sorting nexin SNX17 and PDLIM family proteins

The sorting nexin SNX17 controls endosome-to-cell surface recycling of diverse transmembrane cargo proteins including integrins, the amyloid precursor protein and lipoprotein receptors. This requires association with the multi-subunit Commander trafficking complex, which depends on the C-terminus of SNX17 through unknown mechanisms. Using affinity enrichment proteomics, we find that a C-terminal peptide of SNX17 is not only sufficient for Commander interaction but also associates with members of the actin-associated PDZ and LIM domain (PDLIM) family. We show that SNX17 contains a type III PSD95/Dlg/Zo1 (PDZ) binding motif (PDZbm) that binds specifically to the PDZ domains of PDLIM family proteins but not to other PDZ domains tested. The structure of the PDLIM7 PDZ domain bound to the SNX17 C-terminus was determined by NMR spectroscopy and reveals an unconventional perpendicular peptide interaction. Mutagenesis confirms the interaction is mediated by specific electrostatic contacts and a uniquely conserved proline-containing loop sequence in the PDLIM protein family. Our results define the mechanism of SNX17-PDLIM interaction and suggest that the PDLIM proteins may play a role in regulating the activity of SNX17 in conjunction with Commander and actin-rich endosomal trafficking domains.

biochemistry↗

bioRxiv2021

Gene-gene relationships in an Escherichia coli accessory genome are linked to function and mobility

The pangenome contains all genes encoded by a species, with the core genome present in all strains and the accessory genome in only a subset. Coincident gene relationships are expected within the accessory genome, where the presence or absence of one gene is influenced by the presence or absence of another. Here, we analysed the accessory genome of an Escherichia coli pangenome consisting of 400 genomes from 20 sequence types to identify genes that display significant co-occurrence or avoidance patterns with one another. We present a complex network of genes that are either found together or that avoid one another more often than would be expected by chance, and show that these relationships vary by lineage. We demonstrate that genes co-occur by function, and that several highly connected gene relationships are linked to mobile genetic elements. We find that genes are more likely to co-occur with, rather than avoid, another gene, suggesting that cooperation is more common than conflict in the accessory genome. This work furthers our understanding of the dynamic nature of prokaryote pangenomes and implicates both function and mobility as drivers of gene relationships. Data summaryAll Supplementary Data files and the Python scripts used in the analyses are available at doi.org/10.17639/nott.7103. Impact statementThe pangenome of a species encompasses the core genes encoded by all genomes, as well as the accessory genes found in only a subset. Much remains to be understood about the relationships and interactions between accessory genes; in particular, what drives pairs of genes to appear together in the same genome, or what prevents them from being in the same genome together, more often than expected by chance. How these co-occurrence and avoidance relationships develop, and what effect they have on the dynamics and evolution of the pangenome as a whole, is largely unknown. Here, we present a springboard for understanding prokaryote pangenome evolution by uncovering significant gene relationships in a model Escherichia coli pangenome. We identify mobile genetic elements and the sharing of common function as possible driving forces behind the co-occurrence of accessory genes. Furthermore, this work offers an extensive dataset from which gene relationships could be identified for any gene of interest in this E. coli accessory genome, providing a rich resource for the community.

evolutionary biology↗

bioRxiv2020

De novo macrocyclic peptides for inhibiting, stabilising and probing the function of the Retromer endosomal trafficking complex

The Retromer complex (Vps35-Vps26-Vps29) is essential for endosomal membrane trafficking and signalling. Mutations in Retromer cause late-onset Parkinsons disease, while viral and bacterial pathogens can hijack the complex during cellular infection. To modulate and probe its function we have created a novel series of macrocyclic peptides that bind Retromer with high affinity and specificity. Crystal structures show the majority of cyclic peptides bind to Vps29 via a Pro-Leu-containing sequence, structurally mimicking known interactors such as TBC1D5, and blocking their interaction with Retromer in vitro and in cells. By contrast, macrocyclic peptide RT-L4 binds Retromer at the Vps35-Vps26 interface and is a more effective molecular chaperone than reported small molecules, suggesting a new therapeutic avenue for targeting Retromer. Finally, tagged peptides can be used to probe the cellular localisation of Retromer and its functional interactions in cells, providing novel tools for studying Retromer function.

biochemistry↗

bioRxiv2020

Evidence for selection in a prokaryote pangenome

A pangenome is the complete set of genes (core and accessory) present in a phylogenetic clade. We hypothesize that a pangenomes accessory gene content is structured and maintained by selection. To test this hypothesis, we interrogated the genomes of 40 Pseudomonas genomes for statistically significant coincident (i.e. co-occurring/avoiding) gene patterns. We found that 86.7% of common accessory genes are involved in [≥]1 coincident relationship. Further, genes that co-occur and/or avoid each other - but are not vertically or horizontally co-inherited - are more likely to share Gene Ontology categories, are more likely to be simultaneously transcribed, and are more likely to produce interacting proteins, than would be expected by chance. These results are not due to coincident genes being adjacent to one another on the chromosome. Together, these findings suggest that the accessory genome is structured into interacting sets of genes co-selected to function together within a given strain. Given the simi larity of the Pseudomonas pangenome with open pangenomes of other prokaryotic species, we speculate that these results are generalizable.

microbiology↗