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Davey, J.

Publications and source records attributed to Davey, J..

9 recordsLinked to original sources

Plasmids encode and can mobilize onion pathogenicity in Pantoea agglomerans

Pantoea agglomerans is one of four Pantoea species for which strains have been reported in the United States to cause bacterial rot of onion bulbs. However, not all P. agglomerans strains are pathogenic to onion. We characterized onion-associated strains of P. agglomerans to elucidate the genetic and genomic signatures of onion-pathogenic P. agglomerans. We collected >300 P. agglomerans strains associated with symptomatic onion plants and bulbs from public culture collections, research laboratories, and a multi-year survey in 11 states in the USA. Genome assemblies were generated for 87 P. agglomerans strains that showed a range in onion virulence phenotypes. Combining the 87 genome assemblies with 100 high-quality, public P. agglomerans genome assemblies identified two well-represented and well-supported P. agglomerans phylogroups. Strains causing severe symptoms on onion leaves and bulbs were only identified in Phylogroup II and encoded the HiVir biosynthetic cluster for the phytotoxin pantaphos, supporting the role of HiVir as a crucial pathogenicity factor. Using a MASH-based plasmid classification system, the P. agglomerans HiVir cluster was determined to be encoded in two distinct plasmid contexts: 1) as an accessory gene cluster on a conserved P. agglomerans plasmid (pAggl), or 2) on a mosaic cluster of plasmids common among onion strains (pOnion). Analysis of closed genomes of P. agglomerans revealed that the pOnion plasmids harbored alt genes responsible for encoding tolerance to the thiosulfinate defensive chemistry in Allium spp. Additionally, many of these pOnion plasmids harbored cop gene clusters, which confer resistance to copper. However, the pOnion plasmids encoded the HiVir cluster less frequently. We demonstrated that the pOnion plasmid pCB1C, encoding HiVir and alt clusters as well as an intact conjugative type IV secretion system (T4SS), can act as a natively mobilizable pathogenicity plasmid that transforms P. agglomerans Phylogroup I strains, including environmental strains, into virulent pathogens of onion. This work indicates a central role for plasmids and plasmid ecology in mediating P. agglomerans interactions with onion plants, with potential implications for onion bacterial disease management.

microbiology↗

The Rho GTPase Rac1 mediates exercise training adaptations

Exercise training elicits tremendous health benefits; however, the molecular underpinnings are poorly understood. As one of the most regulated groups of proteins following acute exercise in human muscle, Rho GTPases are unexplored candidates for mediating the beneficial effects of exercise. The Rho GTPase Rac1 was activated during multiple exercise modalities and remained elevated hours after resistance exercise in human muscle. Inducible muscle-specific Rac1 knockout (Rac1 imKO) mice, displayed attenuated muscle protein synthesis, glycogen resynthesis and p38 MAPK signaling in recovery from contractions. Exercise training upregulated Rac1 protein content in human and mouse muscle. Overexpression of hyperactive Rac1 elevated reactive oxidant species production during exercise yet did not induce a trained muscle phenotype. In Rac1 imKO mice, the improvements in running capacity and muscle mass after exercise training were diminished. Using gain- and loss-of-function mouse models and human muscle biopsies, we identify Rac1 as a regulator of exercise training adaptions. HighlightsO_LIVarious exercise modalities activate Rac1 signaling in human skeletal muscle. C_LIO_LIHSP27, MNK1, and CREB are Rac1-dependent contraction-responsive targets in muscle. C_LIO_LIPost-contraction protein synthesis requires Rac1 but not NOX2. C_LIO_LIRac1-NOX2 signaling is necessary for post-contraction glycogen resynthesis. C_LIO_LIExercise training increases Rac1 protein content in human and mouse muscles. C_LIO_LIRac1 mediates critical adaptations to exercise training. C_LI

molecular biology↗

Comparisons between Complete Genomes of the Eukaryotic Extremophile Galdieria sulphuraria Reveals Complex Nuclear Chromosomal Structures

Extremophiles, while typically bacteria and archaea, are also found in the eukaryotic domain of life. The eukaryote Galdieria sulphuraria is a thermoacidophilic red alga belonging to the class Cyanidiophyceae, an especially unique class as it comprises the basal clade of eukaryotic extremophiles. Galdieria species can grow both photosynthetically and heterotrophically on a variety of carbon sources, thriving down to pH 0 and temperatures up to 56 {degrees}C, while tolerating high levels of reactive oxygen species and high levels of heavy metals. Here we report whole-genome sequencing of three G. sulphuraria strains, uncovering a compact (13.1 Mb - 16.0 Mb) nuclear genome with 72-73 chromosomes, dependent on the strain.Comparative analyses of the macro synteny revealed significant structural rearrangement between G. sulphuraria isolates and the genome shows signs of sexual recombination. This, along with the large number of nuclear chromosomes compared to the genome size, reveals a mechanism of intrinsic adaptability in this eukaryotic extremophile, uncovering how G. sulphuraria can thrive in a rapidly changing extreme environment.

genomics↗

A novel terpene synthase produces an anti-aphrodisiac pheromone in the butterfly Heliconius melpomene

Terpenes, a group of structurally diverse compounds, are the biggest class of secondary metabolites. While the biosynthesis of terpenes by enzymes known as terpene synthases (TPSs) has been described in plants and microorganisms, few TPSs have been identified in insects, despite the presence of terpenes in multiple insect species. Indeed, in many insect species, it remains unclear whether terpenes are sequestered from plants or biosynthesised de novo. No homologs of plant TPSs have been found in insect genomes, though insect TPSs with an independent evolutionary origin have been found in Hemiptera and Coleoptera. In the butterfly Heliconius melpomene, the monoterpene (E)-{beta}-ocimene acts as an anti-aphrodisiac pheromone, where it is transferred during mating from males to females to avoid re-mating by deterring males. To date only one insect monoterpene synthase has been described, in Ips pini (Coleoptera), and is a multifunctional TPS and isoprenyl diphosphate synthase (IDS). Here, we combine linkage mapping and expression studies to identify candidate genes involved in the biosynthesis of (E)-{beta}-ocimene. We confirm that H. melpomene has two enzymes that exhibit TPS activity, and one of these, HMEL037106g1 is able to synthesise (E)-{beta}-ocimene in vitro. Unlike the enzyme in Ips pini, these enzymes only exhibit residual IDS activity, suggesting they are more specialised TPSs, akin to those found in plants. Phylogenetic analysis shows that these enzymes are unrelated to previously described plant and insect TPSs. The distinct evolutionary origin of TPSs in Lepidoptera suggests that they have evolved multiple times in insects.\n\nSignificance statementTerpenes are a diverse class of natural compounds, used by both plants and animals for a variety of functions, including chemical communication. In insects it is often unclear whether they are synthesised de novo or sequestered from plants. Some plants and insects have converged to use the same compounds. For instance, (E)-{beta}-ocimene is a common component of floral scent and is also used by the butterfly Heliconius melpomene as an anti-aphrodisiac pheromone. We describe two novel terpene synthases, one of which synthesises (E)-{beta}-ocimene in H. melpomene, unrelated not only to plant enzymes but also other recently identified insect terpene synthases. This provides the first evidence that the ability to synthesise terpenes has arisen multiple times independently within the insects.

biochemistry↗

Mechanisms involved in follistatin-induced increased insulin action in skeletal muscle

BackgroundSkeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor {beta} (TGF-{beta}) superfamily, including activin A, which causes atrophy. TGF-{beta} superfamily ligands also negatively regulate insulin-sensitive proteins, but whether this pathway contributes to insulin action remains to be determined.\n\nMethodsTo elucidate if TGF-{beta} superfamily ligands regulate insulin action we used an adeno-associated virus gene editing approach to overexpress the activin A inhibitor, follistatin (Fst288) in mouse muscle of lean and diet-induced obese mice. We determined basal and insulin-stimulated 2 deoxy-glucose uptake using isotopic tracers in vivo. Furthermore, to evaluate whether circulating Fst and activin A concentrations are associated with obesity, insulin resistance, and weight loss in humans we analysed serum from morbidly obese subjects before, 1 week, and 1 year after Roux-en-Y gastric bypass (RYGB).\n\nResultsFst288 muscle overexpression markedly increased in vivo insulin-stimulated (but not basal) glucose uptake (+75%, p<0.05) and increased protein expression and intracellular insulin signalling of AKT, TBC1D4, PAK1, PDH-E1, and p70S6K (p<0.05). No correlation was observed between the Fst288-driven hypertrophy and the increase in insulin-stimulated glucose uptake but Fst288 increased basal and insulin-stimulated protein synthesis. Importantly, Fst288 completely normalized muscle glucose uptake in insulin-resistant diet-induced obese mice. RYGB surgery doubled circulating Fst and reduced Activin A (-24%, p<0.05) concentration 1 week after surgery before any significant weight loss in morbidly obese normoglycemic patients, while major weight loss after 1 year did not further change the concentrations.\n\nConclusionsWe here present evidence that Fst is a potent regulator of insulin action in muscle and in addition to AKT and p70S6K, we identify TBC1D1, TBC1D4 and PAK1 as Fst targets. A possible role for Fst in regulating glycemic control is suggested because circulating Fst more than doubled post RYGB surgery, a treatment that markedly improved insulin sensitivity. These findings demonstrate the therapeutic potential of inhibiting TGF-{beta} superfamily ligands to improve insulin action and Fsts relevance to muscle wasting associated insulin resistant conditions in mice and humans.

physiology↗

Genomic architecture and introgression shape a butterfly radiation

We here pioneer a low-cost assembly strategy for 20 Heliconiini genomes to characterize the evolutionary history of the rapidly radiating genus Heliconius. A bifurcating tree provides a poor fit to the data, and we therefore explore a reticulate phylogeny for Heliconius. We probe the genomic architecture of gene flow, and develop a new method to distinguish incomplete lineage sorting from introgression. We find that most loci with non-canonical histories arose through introgression, and are strongly underrepresented in regions of low recombination and high gene density. This is expected if introgressed alleles are more likely to be purged in such regions due to tighter linkage with incompatibility loci. Finally, we identify a hitherto unrecognized inversion, and show it is a convergent structural rearrangement that captures a known color pattern switch locus within the genus. Our multi-genome assembly approach enables an improved understanding of adaptive radiation.

evolutionary biology↗

Generalisation behaviour of predators toward warning signals displayed by harmful prey: answers from a video-game played by humans.

The persistence of several warning signals in sympatry is a puzzling evolutionary question because selection favours convergence of colour patterns among toxic species. Such convergence is shaped by predators reaction to similar but not identical stimulus, i.e. generalisation behaviour. However, studying generalisation behaviour in complex natural communities of predators is challenging, and is thus generally limited to simple variations of prey colour patterns. Here, we used humans as surrogate predators to investigate generalisation behaviours on two prey communities with different level of warning signals complexity. Humans generalisation capacities were estimated using a computer game simulating a simple (4 morphs) and a complex (10 morphs) community of defended (associated with a penalty) and palatable butterflies. Colour patterns used in the game are actually observed in natural populations of the defended butterflies H. numata, and generalisation behaviour of natural predators communities on these colour patterns have previously been investigated in the wild, allowing direct comparison with human behaviour. We investigated human predation behaviour by recording attack rates on the different defended and palatable colour patterns, as well as player survival time (i.e. score). Phenotypic similarity among the different colour patterns was precisely quantified using a custom algorithm accounting for both colour and pattern variations (CPM method). By analysing attack behaviours of 491 game players, we found that learning was more efficient in the simple prey community. Additionally, profitable prey gained protection from sharing key visual features with unprofitable prey in both communities while learning, in accordance with natural predator behaviours. Moreover, other behaviours observed in natural predators, such as colour neophobia, were detected in humans and shaped morph vulnerability during the game. Similarities between our results in humans and the reaction of natural predator communities to the same colour patterns validate our video-game as a useful proxy to study predator behaviour. This experimental set-up can thus be compared to natural systems, enabling further investigations of generalisation on mimicry evolution.

evolutionary biology↗

Recombination rate variation shapes barriers to introgression across butterfly genomes

Hybridisation and introgression can dramatically alter the relationships among groups of species, leading to phylogenetic discordance across the genome and between populations. Introgression can also erode species differences over time, but selection against introgression at certain loci acts to maintain post-mating species barriers. Theory predicts that species barriers made up of many loci throughout the genome should lead to a broad correlation between introgression and recombination rate, which determines the extent to which selection on deleterious foreign alleles will affect neutral alleles at physically linked loci. Here we describe the variation in genealogical relationships across the genome among three species of Heliconius butterflies: H. melpomene, H. cydno and H. timareta, using whole genomes of 92 individuals, and ask whether this variation can be explained by heterogeneous barriers to introgression. We find that species relationships vary predictably at the chromosomal scale. By quantifying recombination rate and admixture proportions, we then show that rates of introgression are predicted by variation in recombination rate. This implies that species barriers are highly polygenic, with selection acting against introgressed alleles across most of the genome. In addition, long chromosomes, which have lower recombination rates, produce stronger barriers on average than short chromosomes. Finally, we find a consistent difference between two species pairs on either side of the Andes, which suggests differences in the architecture of the species barriers. Our findings illustrate how the combined effects of hybridisation, recombination and natural selection, acting at multitudes of loci over long periods, can dramatically sculpt the phylogenetic relationships among species.

evolutionary biology↗

Genetic dissection of assortative mating behavior

The evolution of new species is made easier when traits under divergent ecological selection are also mating cues. Such ecological mating cues are now considered more common than previously thought, but we still know little about the genetic changes underlying their evolution, or more generally about the genetic basis for assortative mating behaviors. The warning patterns of Heliconius melpomene and H. cydno are under disruptive selection due to increased predation of non-mimetic hybrids, and are used during mate recognition. We carried out a genome-wide quantitative trait locus (QTL) analysis of preference behaviors between these species and showed that divergent male preference has a simple genetic basis. Three QTLs each explain a large proportion of the differences in preference behavior observed between the parental species. Two of these QTLs are on chromosomes with major color pattern genes, including one that is tightly associated with the gene optix. Different loci influence different aspects of attraction, suggesting that behavioral isolation in Heliconius involves the evolution of independently segregating modules, similar to those for the corresponding wing pattern cues. Hybridization and subsequent sharing of wing pattern loci has played an important role during adaptation and speciation in Heliconius butterflies. The existence of large effect preference loci could similarly assist the evolution of novel behavioral phenotypes through recombination and introgression, and should facilitate rapid speciation.

evolutionary biology↗