Biology subjects

Wilson, A. J.

Publications and source records attributed to Wilson, A. J..

29 records · Page 2Linked to original sources

bioRxiv2020

Loss of a plant receptor kinase recruits beneficial rhizosphere-associated Pseudomonas

Maintaining microbiome structure is critical for the health of both plants1 and animals2. In plants, enrichment of beneficial bacteria is associated with advantageous outcomes including protection from biotic and abiotic stress3,4. However, the genetic and molecular mechanisms by which plants enrich for specific beneficial microbes without general dysbiosis have remained elusive. Here we show that through regulation of NADPH oxidase, FERONIA kinase negatively regulates beneficial Pseudomonas fluorescens in the Arabidopsis rhizosphere microbiome. By rescreening a collection of Arabidopsis mutants that affect root immunity under gnotobiotic conditions, followed by microbiome sequencing in natural soil, we identified a FERONIA mutant (fer-8) with a rhizosphere microbiome enriched in P. fluorescens without phylum-level dysbiosis. Using microbiome transplant experiments, we found that the fer-8 microbiome was beneficial and promoted plant growth. The effect of FER on rhizosphere Pseudomonads was independent of its immune coreceptor function, role in development, and jasmonic acid autoimmunity. We found that the fer-8 mutant has reduced basal levels of reactive oxygen species (ROS) in roots and that mutants deficient in NADPH oxidase showed elevated rhizosphere Pseudomonad levels. Overexpression of the ROP2 gene (encoding a client of FER and positive regulator of NADPH oxidase5) in fer-8 plants suppressed Pseudomonad overgrowth. This work shows that FER-mediated ROS production regulates levels of beneficial Pseudomonads in the rhizosphere microbiome.

plant biology↗

bioRxiv2020

Natural selection reverses the exaggeration of a male sexually selected trait, which increases female fitness.

Theory shows how sexual selection can exaggerate male traits beyond naturally selected optima and also how natural selection can ultimately halt trait elaboration. Empirical evidence supports this theory, but to date, there have been no experimental evolution studies directly testing this logic, and little examination of possible associated effects on female fitness. Here we used experimental evolution of replicate populations of broad-horned flour-beetles to test for evolutionary effects of sex-specific predation on an exaggerated sexually selected male trait, while also testing for effects on female lifetime reproductive success. We found that populations subjected to male-specific predation evolved smaller sexually selected traits and this indirectly increased female fitness, seemingly through intersexual genetic correlations we documented. Predation solely on females had no effects. Our findings support fundamental theory, but also reveal novel outcomes when natural selection targets sex-limited sexually selected characters.

evolutionary biology↗

bioRxiv2020

Quantifying the acquisition and retention of lumpy skin disease virus by haematophagus insects and the implications for transmission and control.

Lumpy skin disease virus (LSDV), a poxvirus that causes severe disease in cattle, has in the last few years rapidly extended its distribution from Africa and the Middle East into Europe, Russia, and across Asia. LSDV is believed to be primarily spread mechanically by blood-feeding arthropods, however the exact mode of arthropod transmission, the relative ability of different arthropod species to acquire and retain the virus, as well as their comparative importance for LSDV transmission, remain poorly characterised. Since the vector-borne nature of LSDV transmission is believed to have enabled the rapid geographic expansion of this virus, the lack of quantitative evidence on LSDV transmission has impeded effective control of the disease during the current epidemic. Obtaining high quality data on virus transmission by arthropods is challenging, and practical limitations often result in inadequate arthropod numbers or model hosts, limiting the transferability of experimental findings to the natural transmission scenario. We have addressed these limitations in this study. Using a highly representative bovine experimental model of lumpy skin disease we allowed four representative vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) to blood-feed on LSDV-inoculated cattle in order to examine the acquisition and retention of LSDV by these species in unprecedented detail. We found the probability of LSDV transmission from clinical cattle to vector correlated with disease severity. Subclinical disease was more common than clinical disease in the inoculated cattle, however the probability of vectors acquiring LSDV from subclinical animals was very low. All four potential vector species studied had a similar rate of acquisition of LSDV after feeding on the host, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in the in-vivo transmission experiments subsequently enabled enhanced modelling approaches to determine the basic reproduction number of LSDV in cattle mediated by each of the insect species. This was highest for Stomoxys calcitrans (19.1), C. nubeculosus (7.4), and Ae. aegypti (2.4), surprisingly indicating these three species are all potentially efficient transmitters of LSDV. These results reveal that currently applied LSDV control measures such as stamping out of all cattle on affected premises or insect control measures targeting single species need to be urgently reconsidered. Overall our studies have highlighted that the combination of highly relevant in-vivo experiments and mathematical modelling can be directly applied to devise evidence-based proportionate and targeted control programmes.

microbiology↗

bioRxiv2020

Cognitive performance and stress responsiveness in the Trinidadian Guppy: a multivariate approach

Cognition is vital for carrying out behaviours required for survival and reproduction. In animals, we now know that cognitive performance varies not just among species, but also among individuals within populations. While this variation is a prerequisite for contemporary natural selection, it is also true that selection does not act on traits in isolation. The extent to which cognitive traits covary with other aspects of phenotype (e.g. personality traits) is therefore expected to be an important factor in shaping evolutionary dynamics. Here we adopt a multivariate approach to test for spatial learning ability in a captive population of male Trinidadian guppies (Poecilia reticulata), and ask whether differences in cognitive performance are associated with (repeatable) differences in stress response behaviour. We focus on stress response for two reasons. First, functional links between cognitive traits and stress coping style have been hypothesised. Second, individual-level studies of cognitive performance typically rely on multiple testing paradigms that may themselves be a stressor. Thus, there is a risk that variation in stress responsiveness is itself a cause of apparent, but artefactual variance in cognitive ability. Using a set of fish exposed repeatedly to two distinct spatial learning tasks (maze layouts), and an acute stress response test (open field trial), we find differences among-individuals in task performance that are repeatable within- and across maze layouts. On average performance improves with experience in the first maze, consistent with spatial learning, but not in the second. In both mazes, there is among-individual variation in the trajectory of mean performance with trial number suggesting individuals differ in learning rate. Acute stress response behaviour is repeatable but predicts neither average time to solve the maze nor learning rate. We thus find no support for among-individual correlation between acute stress response and cognitive performance. However, we highlight the possibility that cumulative, chronic stress effects may nonetheless cause observed declines in performance across repeats for some individuals (leading to lack of improvement in mean time to solve the second maze). If so, this may represent a pervasive but difficult challenge for our ability to robustly estimate learning rates in studies of animal cognition.

animal behavior and cognition↗

bioRxiv2019

Inter-domain dynamics in the chaperone SurA and multi-site binding to its unfolded outer membrane protein clients

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but how it binds its OMP clients and the mechanism(s) of its chaperone action remain unclear. Here, we have used chemical cross-linking, hydrogen-deuterium exchange, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and to interrogate the role of conformational dynamics of the chaperones domains in OMP recognition. We demonstrate that SurA samples a broad array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested by its crystal structure. Multiple binding sites for OMPs are located primarily in the core domain, with binding of the unfolded OMP resulting in conformational changes between the core/P1 domains. Together, the results portray a model in which unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between its domains assisting OMP recognition, binding and release.

biochemistry↗

bioRxiv2019

Adenita: Interactive 3D modeling and visualization of DNA nanostructures

We present Adenita, a novel software tool for the design of DNA nanostructures in a user-friendly integrated environment for molecular modeling. Adenita is capable of handling large DNA origami structures, re-use them as building blocks of new designs and provide on demand feedback, thus overcoming effectively some of the limitations of existing tools. Additionally, it integrates all major established approaches to DNA nanostructure design (DNA origami, wireframe nanostructures and DNA tiles) and allows to combine them. We show-case Adenita by re-using a large nanorod designed with Cadnano [1] to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.

bioinformatics↗

bioRxiv2019

Genetic integration of the stress response

The vertebrate stress response comprises a suite of behavioural and physiological traits that must be functionally integrated to ensure organisms cope adaptively with acute stressors. Natural selection should favour functional integration, leading to a prediction of genetic integration of these traits. Despite the implications of such genetic integration for our understanding of human and animal health, as well as evolutionary responses to natural and anthropogenic stressors, formal quantitative genetic tests of this prediction are lacking. Here we demonstrate that acute stress response components in Trinidadian guppies are both heritable and integrated on the major axis of genetic covariation. This integration could either facilitate or constrain evolutionary responses to selection, depending upon the alignment of selection with this axis. Such integration also suggests artificial selection on the genetically correlated behavioural responses to stress could offer a viable non-invasive route to the improvement of health and welfare in captive animal populations.

evolutionary biology↗

bioRxiv2019

Selective Affimers Recognize BCL-2 Family Proteins Through Non-Canonical Structural Motifs

The BCL-2 family is a challenging set of proteins to target selectively due to sequence and structural homologies across the family. Selective ligands for the BCL-2 family regulators of apoptosis are desirable as probes to understand cell biology and apoptotic signalling pathways, and as starting points for inhibitor design. We have used phage display to isolate Affimer reagents (non-antibody binding proteins based on a conserved scaffold) to identify ligands for MCL-1, BCL-xL, BCL-2, BAK and BAX, then used multiple biophysical characterisation methods to probe the interactions. We established that purified Affimers elicit selective and potent recognition of their target BCL-2 protein. For anti-apoptotic targets, competitive inhibition of their canonical protein-protein interactions is demonstrated. Co-crystal structures reveal an unprecedented mode of molecular recognition; where a BH3 helix is normally bound, flexible loops from the Affimer dock into the BH3 binding cleft. Moreover, the Affimers induce a change in the target proteins towards a desirable drug bound like conformation. These results indicate Affimers can be used as alternative templates to inspire design of selective BCL-2 family modulators, and provide proof-of-concept for the elaboration of selective non-antibody binding reagents for use in cell-biology applications.

biochemistry↗

bioRxiv2018

Habituation and individual variation in the endocrine stress response in the Trinidadian guppy (Poecilia reticulata)

The vertebrate stress response enables individuals to react to and cope with environmental challenges. A crucial aspect of the stress response is the elevation of circulating glucocorticoids. However, continued activation of the stress response under repeated (or chronic) stress can be damaging to fitness. Under certain circumstances it may therefore be adaptive to habituate to repeated exposures to a particular stressor by reducing the magnitude of any associated release of glucocorticoids. Here, we investigate whether Trinidadian guppies (Poecilia reticulata) habituate to repeated exposure to a mild stressor, using a waterborne hormone sampling approach that has previously been shown to elicit a stress response in small fish. We also test for individual variation in the extent of habituation to this stressor. Concentrating on freely circulating cortisol, we found that the first exposure to the assay induced high cortisol release rates but that guppies tended to habituate quickly to subsequent exposures. There were consistent differences among individuals in their average cortisol release rate (after accounting for effects of variables such as body size) over repeated exposures. Our analyses did not find evidence of individual differences in habituation rate, although limitations in statistical power could account for this finding. We also present data on free 11-ketotestosterone, in addition to conjugated forms of both hormones. We discuss consistent individual differences around the general pattern of habituation in the flexible stress response, and highlight the potential for individual variation in habituation to facilitate selection against the deleterious effects of chronic stress.\n\nSummary statementTrinidadian guppies habituate quickly to repeated stress exposure, and exhibit consistent differences in their endocrine stress response. We provide a framework for analysing individual variation in habituation rate.

physiology↗

bioRxiv2018

Indirect effects of territorial neighbors on the timing of spring breeding may counteract changes in selection in North American red squirrels

Organisms can affect one anothers phenotypes when they socially interact. Indirect genetic effects occur when an individuals phenotype is affected by genes expressed in another individual. These heritable effects can enhance or reduce adaptive potential, thereby accelerating or reversing evolutionary change. Quantifying these social effects is therefore crucial for our understanding of evolution, yet estimates of indirect genetic effects in wild animals are limited to dyadic interactions. We estimated indirect phenotypic and genetic effects, and their covariance with direct effects, for the date of spring breeding in North American red squirrels (Tamiasciurus hudsonicus) living in an array of territories of varying spatial proximity. Additionally, we estimated variance parameters and the strength of selection at low and high population densities. Social effects of neighbours on the date of spring breeding were weak at low, but stronger at high population densities. Indirect phenotypic effects accounted for a larger amount of variation in the date of breeding than direct differences among-individuals, although the genetic component to these indirect effects was not statistically significant. Nevertheless, the estimated effect size was large enough to suggest that indirect genetic effects could alter evolutionary change, resulting in less change at high densities despite stronger selection. Despite the difficulty in estimating them precisely, indirect genetic effects have clear potential to alter evolutionary trajectories in any natural systems where organisms interact.

evolutionary biology↗

bioRxiv2018

No Evidence for Systematic White Matter Correlates of Dyslexia and Dyscalculia

Learning disabilities such as dyslexia, dyscalculia and their comorbid manifestation are prevalent, affecting as much as fifteen percent of the population. Structural neuroimaging studies have indicated that these disorders can be related to differences in white matter integrity, although findings remain disparate. In this study, we used a unique design composed of individuals with dyslexia, dyscalculia, both disorders and controls, to systematically explore differences in fractional anisotropy across groups using diffusion tensor imaging. Specifically, we focused on the corona radiata and the arcuate fasciculus, two tracts associated with reading and mathematics in a number of previous studies. Using Bayesian hypothesis testing, we show that the present data favor the null model of no differences between groups for these particular tracts--a finding that seems to go against the current view but might be representative of the disparities within this field of research. Together, these findings suggest that structural differences associated with dyslexia and dyscalculia might not be as reliable as previously thought, with potential ramifications in terms of remediation.

neuroscience↗