Ectopical expression of bacterial collagen-like protein supports its role as adhesin in host-parasite coevolution.

For a profound understanding of antagonistic coevolution, it is necessary to identify the coevolving genes. The bacterium Pasteuria and its host, the microcrustacean Daphnia, are a well-characterized paradigm for co-evolution, but the underlying genes remain largely unknown. A genome-wide association study suggested a Pasteuria collagen-like protein 7 (Pcl7) as a candidate mediating parasite attachment and driving its coevolution with the host. Since Pasteuria ramosa cannot currently be genetically manipulated, we used Bacillus thuringiensis to express a fusion protein of a Pcl7 carboxy-terminus from P. ramosa and the amino-terminal domain of a B. thuringiensis collagen-like protein (CLP). Mutant B. thuringiensis (Pcl7-Bt) spores but not wild-type B. thuringiensis (WT-Bt) spores attached to the same site of susceptible hosts as P. ramosa. Furthermore, Pcl7-Bt spores attached readily to susceptible host genotypes, but only slightly to resistant host genotypes. These findings indicated that the fusion protein was properly expressed and folded and demonstrated that indeed the C-terminus of Pcl7 mediates attachment in a host genotype-specific manner. These results provide strong evidence for the involvement of a CLP in the coevolution of Daphnia and P. ramosa and open new avenues for genetic epidemiological studies of host-parasite interactions.

Evolutionary change in flight-to-light response in urban moths comes with changes in wing morphology.

Moths and other insects are attracted by artificial light sources. This flight-to-light behaviour disrupts their general activity focused on finding resources, such as mating partners, and increases predation risk. It thus has substantial fitness costs. In illuminated urban areas, spindle ermine moths Yponomeuta cagnagella were reported to have evolved a reduced flight-to-light response. Yet, the specific mechanism remained unknown, and was hypothesized to involve either changes in visual perception or general flight ability or overall mobility traits. Here, we test whether spindle ermine moths from urban and rural populations-with known differences in flight-to-light responses-differ in flight-related morphological traits. Urban individuals were found to have on average smaller wings than rural moths, which in turn correlated with a lower probability of being attracted to an artificial light source. Our finding supports the reduced mobility hypothesis, which states that reduced mobility in urban areas is associated with specific morphological changes in the flight apparatus.

The limits of stress-tolerance for zooplankton resting stages in freshwater ponds.

In seasonal environments, many organisms evolve strategies such as diapause to survive stressful periods. Understanding the link between habitat stability and diapause strategy can help predict a population's survival in a changing world. Indeed, resting stages may be an important way freshwater organisms can survive periods of drought or freezing, and as the frequency and extent of drought or freezing vary strongly among habitats and are predicted to change with climate change, it raises questions about how organisms cope with, and survive, environmental stress. Using Daphnia magna as a model system, we tested the ability of resting stages from different populations to cope with stress during diapause. The combination of elevated temperatures and wet conditions during diapause shows to prevent hatching altogether. In contrast, hatching is relatively higher after a dry and warm diapause, but declines with rising temperatures, while time to hatch increases. Resting stages produced by populations from summer-dry habitats perform slightly, but consistently, better at higher temperatures and dryness, supporting the local adaptation hypothesis. A higher trehalose content in resting eggs from summer-dry habitat might explain such pattern. Considering that temperatures and summer droughts are projected to increase in upcoming years, it is fundamental to know how resting stages resist stressful conditions so as to predict and protect the ecological functioning of freshwater ecosystems.

Near chromosome-level genome assembly of the microsporidium Hamiltosporidium tvaerminnensis.

Microsporidia are intracellular parasitic fungi whose genomes rank among the smallest of all known eukaryotes. A number of outstanding questions remain concerning the evolution of their large-scale variation in genome architecture, responsible for genome size variation of more than an order of magnitude. This genome report presents the first near-chromosomal assembly of a large-genome microsporidium, Hamiltosporidium tvaerminnensis. Combined Oxford Nanopore, Pacific Biosciences (PacBio), and Illumina sequencing led to a genome assembly of 17 contigs, 11 of which represent complete chromosomes. Our assembly is 21.64 Mb in length, has an N50 of 1.44 Mb, and consists of 39.56% interspersed repeats. We introduce a novel approach in microsporidia, PacBio Iso-Seq, as part of a larger annotation pipeline for obtaining high-quality annotations of 3,573 protein-coding genes. Based on direct evidence from the full-length Iso-Seq transcripts, we present evidence for alternative polyadenylation and variation in splicing efficiency, which are potential regulation mechanisms for gene expression in microsporidia. The generated high-quality genome assembly is a necessary resource for comparative genomics that will help elucidate the evolution of genome architecture in response to intracellular parasitism.

Uncovering the Genomic Basis of Infection Through Co-genomic Sequencing of Hosts and Parasites.

Understanding the genomic basis of infectious disease is a fundamental objective in co-evolutionary theory with relevance to healthcare, agriculture, and epidemiology. Models of host-parasite co-evolution often assume that infection requires specific combinations of host and parasite genotypes. Co-evolving host and parasite loci are, therefore, expected to show associations that reflect an underlying infection/resistance allele matrix, yet little evidence for such genome-to-genome interactions has been observed among natural populations. We conducted a study to search for this genomic signature across 258 linked host (Daphnia magna) and parasite (Pasteuria ramosa) genomes. Our results show a clear signal of genomic association between multiple epistatically interacting loci in the host genome, and a family of genes encoding for collagen-like protein in the parasite genome. These findings are supported by laboratory-based infection trials, which show strong correspondence between phenotype and genotype at the identified loci. Our study provides clear genomic evidence of antagonistic co-evolution among wild populations.

QTL study reveals candidate genes underlying host resistance in a Red Queen model system.

Specific interactions of host and parasite genotypes can lead to balancing selection, maintaining genetic diversity within populations. In order to understand the drivers of such specific coevolution, it is necessary to identify the molecular underpinnings of these genotypic interactions. Here, we investigate the genetic basis of resistance in the crustacean host, Daphnia magna, to attachment and subsequent infection by the bacterial parasite, Pasteuria ramosa. We discover a single locus with Mendelian segregation (3:1 ratio) with resistance being dominant, which we call the F locus. We use QTL analysis and fine mapping to localize the F locus to a 28.8-kb region in the host genome, adjacent to a known resistance supergene. We compare the 28.8-kb region in the two QTL parents to identify differences between host genotypes that are resistant versus susceptible to attachment and infection by the parasite. We identify 13 genes in the region, from which we highlight eight biological candidates for the F locus, based on presence/absence polymorphisms and differential gene expression. The top candidates include a fucosyltransferase gene that is only present in one of the two QTL parents, as well as several Cladoceran-specific genes belonging to a large family that is represented in multiple locations of the host genome. Fucosyltransferases have been linked to resistance in previous studies of Daphnia-Pasteuria and other host-parasite systems, suggesting that P. ramosa spore attachment could be mediated by changes in glycan structures on D. magna cuticle proteins. The Cladoceran-specific candidate genes suggest a resistance strategy that relies on gene duplication. Our results add a new locus to a growing genetic model of resistance in the D. magna-P. ramosa system. The identified candidate genes will be used in future functional genetic studies, with the ultimate aim to test for cycles of allele frequencies in natural populations.

Left insular cortical thinning differentiates the inattentive and combined subtype of adult attention-deficit/hyperactivity disorder.

BACKGROUND: Neuroimaging studies in attention-deficit/hyperactivity disorder (ADHD) demonstrated decreased global gray matter volume. In terms of surface parameters, most investigations focused on cortical thickness with a multi-center MEGA-analysis indicating cortical thinning in children, but not in adults with ADHD. In this single-scanner study, for the first time in adult ADHD, we additionally examined metrics beyond cortical thickness and surface area, namely sulcal depth and fractal dimension as measures of cortical alteration and complexity. Unlike most previous studies, ADHD subtypes were considered. METHODS: As part of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), surface parameters were analyzed in 131 adults with ADHD (66 combined, 60 inattentive and 5 hyperactive/impulsive subtype) and 95 healthy controls with the Computational Anatomy Toolbox (CAT12) using Statistical Parametric Mapping Software (SPM). RESULTS: Neither at the vertex- nor at the region of interest-level, the ADHD and control group differed significantly with regard to cortical thickness, gyrification index, sulcal depth or fractal dimension. Contrasting the combined and the inattentive subtype, patients of the combined subtype showed a significant thinning of the left anterior insular cortex. Thinner left pars opercularis cortical thickness was associated with symptoms of hyperactivity/restlessness. CONCLUSIONS: Resembling previous findings of a correlation of the left anterior insular gray matter volume with oppositional symptoms in adolescents with ADHD, we detected left anterior insular cortical thinning in the ADHD combined subtype. Left insular cortical thickness could represent a potential marker to distinguish the predominantly inattentive and the combined ADHD subtype in adulthood.

Population genetic analysis of the microsporidium Ordospora colligata reveals the role of natural selection and phylogeography on its extremely compact and reduced genome.

The determinants of variation in a species' genome-wide nucleotide diversity include historical, environmental, and stochastic aspects. This diversity can inform us about the species' past and present evolutionary dynamics. In parasites, the mode of transmission and the interactions with the host might supersede the effects of these aspects in shaping parasite genomic diversity. We used genomic samples from 10 populations of the microsporidian parasite Ordospora colligata to investigate present genomic diversity and how it was shaped by evolutionary processes, specifically, the role of phylogeography, co-phylogeography (with the host), natural selection, and transmission mode. Although very closely related microsporidia cause diseases in humans, O. colligata is specific to the freshwater crustacean Daphnia magna and has one of the smallest known eukaryotic genomes. We found an overlapping phylogeography between O. colligata and its host highlighting the long-term, intimate relationship between them. The observed geographic distribution reflects previous findings that O. colligata exhibits adaptations to colder habitats, which differentiates it from other microsporidian gut parasites of D. magna predominantly found in warmer areas. The co-phylogeography allowed us to calibrate the O. colligata phylogeny and thus estimate its mutation rate. We identified several genetic regions under potential selection. Our whole-genome study provides insights into the evolution of one of the most reduced eukaryotic genomes and shows how different processes shape genomic diversity of an obligate parasite.

Retinal Thinning in Adults with Autism Spectrum Disorder.

Since the retina shares its embryological origin with the central nervous system, optical coherence tomography (OCT), an imaging technique frequently employed in ophthalmology to analyze the macula and intraretinal layer thicknesses and volumes, has recently become increasingly important in psychiatric research. We examined 34 autistic and 31 neurotypical adults (NT) using OCT. Autistic adults had reduced overall macular and outer nuclear layer (ONL) thickness and volume compared to NT. Both macular and ONL thickness showed significant inverse associations with the severity of autistic symptoms measured with the Social Responsiveness Scale 2 (SRS-2). Longitudinal studies across different age groups are required to clarify whether retinal changes may represent a possible trait marker.

Genetic Drift Shapes the Evolution of a Highly Dynamic Metapopulation.

The dynamics of extinction and (re)colonization in habitat patches are characterizing features of dynamic metapopulations, causing them to evolve differently than large, stable populations. The propagule model, which assumes genetic bottlenecks during colonization, posits that newly founded subpopulations have low genetic diversity and are genetically highly differentiated from each other. Immigration may then increase diversity and decrease differentiation between subpopulations. Thus, older and/or less isolated subpopulations are expected to have higher genetic diversity and less genetic differentiation. We tested this theory using whole-genome pool-sequencing to characterize nucleotide diversity and differentiation in 60 subpopulations of a natural metapopulation of the cyclical parthenogen Daphnia magna. For comparison, we characterized diversity in a single, large, and stable D. magna population. We found reduced (synonymous) genomic diversity, a proxy for effective population size, weak purifying selection, and low rates of adaptive evolution in the metapopulation compared with the large, stable population. These differences suggest that genetic bottlenecks during colonization reduce effective population sizes, which leads to strong genetic drift and reduced selection efficacy in the metapopulation. Consistent with the propagule model, we found lower diversity and increased differentiation in younger and also in more isolated subpopulations. Our study sheds light on the genomic consequences of extinction-(re)colonization dynamics to an unprecedented degree, giving strong support for the propagule model. We demonstrate that the metapopulation evolves differently from a large, stable population and that evolution is largely driven by genetic drift.

Genetic slippage after sex maintains diversity for parasite resistance in a natural host population.

Although parasite-mediated selection is a major driver of host evolution, its influence on genetic variation for parasite resistance is not yet well understood. We monitored resistance in a large population of the planktonic crustacean Daphnia magna over 8 years, as it underwent yearly epidemics of the bacterial pathogen Pasteuria ramosa. We observed cyclic dynamics of resistance: Resistance increased throughout the epidemics, but susceptibility was restored each spring when hosts hatched from sexual resting stages. Host resting stages collected across the year showed that largely resistant host populations can produce susceptible sexual offspring. A genetic model of resistance developed for this host-parasite system, based on multiple loci and strong epistasis, is in partial agreement with our findings. Our results reveal that, despite strong selection for resistance in a natural host population, genetic slippage after sexual reproduction can be a strong factor for the maintenance of genetic diversity of host resistance.

Electroretinography in adults with high-functioning autism spectrum disorder.

The electroretinogram (ERG) allows the investigation of retinal signaling pathways and has increasingly been applied in individuals with mental disorders in search for potential biomarkers of neurodevelopmental disorders. Preceding ERG examinations in individuals with autism spectrum disorders (ASD) showed inconsistent results, which might be due to the small number of participants, heterogeneity of the ASD population, differences in age ranges, and stimulation methods. The aim of this study was to investigate functional retinal responses in adults with ASD by means of the light-adapted (photopic) ERG. Light-adapted ERG measurements were obtained with the RETeval® system applying three different stimulation protocols. In the final analysis, the ERG parameters a-wave, b-wave, the photopic negative response (PhNR), the photopic hill parameters as well as additional amplitude ratios were compared between 32 adults with high-functioning ASD and 31 non-autistic controls. Both groups were matched with regard to sex and age. No significant functional retinal differences in amplitude or peak time of the a- or b-wave, PhNR, the photopic hill parameters or the ERG-amplitude ratios could be detected in individuals with ASD compared to non-autistic participants. The absence of electrophysiological functional retinal alterations in ASD, suggests that changes in visual perception, such as increased attention to detail or visual hypersensitivity in ASD, are not due to impairments at early levels of retinal signal processing.

Multispecies coexistence in fragmented landscapes.

Spatial dynamics have long been recognized as an important driver of biodiversity. However, our understanding of species' coexistence under realistic landscape configurations has been limited by lack of adequate analytical tools. To fill this gap, we develop a spatially explicit metacommunity model of multiple competing species and derive analytical criteria for their coexistence in fragmented heterogeneous landscapes. Specifically, we propose measures of niche and fitness differences for metacommunities, which clarify how spatial dynamics and habitat configuration interact with local competition to determine coexistence of species. We parameterize our model with a Bayesian approach using a 36-y time-series dataset of three Daphnia species in a rockpool metacommunity covering >500 patches. Our results illustrate the emergence of interspecific variation in extinction and recolonization processes, including their dependencies on habitat size and environmental temperature. We find that such interspecific variation contributes to the coexistence of Daphnia species by reducing fitness differences and increasing niche differences. Additionally, our parameterized model allows separating the effects of habitat destruction and temperature change on species extinction. By integrating coexistence theory and metacommunity theory, our study provides platforms to increase our understanding of species' coexistence in fragmented heterogeneous landscapes and the response of biodiversity to environmental changes.

Structural and functional retinal alterations in patients with paranoid schizophrenia.

Ophthalmological methods have increasingly raised the interest of neuropsychiatric specialists. While the integrity of the retinal cell functions can be evaluated with the electroretinogram (ERG), optical coherence tomography (OCT) allows a structural investigation of retinal layer thicknesses. Previous studies indicate possible functional and structural retinal alterations in patients with schizophrenia. Twenty-five patients with paranoid schizophrenia and 25 healthy controls (HC) matched for age, sex, and smoking status participated in this study. Both, ERG and OCT were applied to obtain further insights into functional and structural retinal alterations. A significantly reduced a-wave amplitude and thickness of the corresponding para- and perifoveal outer nuclear layer (ONL) was detected in patients with paranoid schizophrenia with a positive correlation between both measurement parameters. Amplitude and peak time of the photopic negative response (PhNR) and thickness of the parafoveal ganglion cell layer (GCL) were decreased in patients with schizophrenia compared to HC. Our results show both structural and functional retinal differences between patients with paranoid schizophrenia and HC. We therefore recommend the comprehensive assessment of the visual system of patients with schizophrenia, especially to further investigate the effect of antipsychotic medication, the duration of illness, or other factors such as inflammatory or neurodegenerative processes. Moreover, longitudinal studies are required to investigate whether the functional alterations precede the structural changes.

Daphnia as a versatile model system in ecology and evolution.

Water fleas of the genus Daphnia have been a model system for hundreds of years and is among the best studied ecological model organisms to date. Daphnia are planktonic crustaceans with a cyclic parthenogenetic life-cycle. They have a nearly worldwide distribution, inhabiting standing fresh- and brackish water bodies, from small temporary pools to large lakes. Their predominantly asexual reproduction allows for the study of phenotypes excluding genetic variation, enabling us to separate genetic from non-genetic effects. Daphnia are often used in studies related to ecotoxicology, predator-induced defence, host-parasite interactions, phenotypic plasticity and, increasingly, in evolutionary genomics. The most commonly studied species are Daphnia magna and D. pulex, for which a rapidly increasing number of genetic and genomic tools are available. Here, I review current research topics, where the Daphnia model system plays a critical role.

Unraveling coevolutionary dynamics using ecological genomics.

Coevolutionary interactions, from the delicate co-dependency in mutualistic interactions to the antagonistic relationship of hosts and parasites, are a ubiquitous driver of adaptation. Surprisingly, little is known about the genomic processes underlying coevolution in an ecological context. However, species comprise genetically differentiated populations that interact with temporally variable abiotic and biotic environments. We discuss the recent advances in coevolutionary theory and genomics as well as shortcomings, to identify coevolving genes that take into account this spatial and temporal variability of coevolution, and propose a practical guide to understand the dynamic of coevolution using an ecological genomics lens.

Increased prefrontal GABA concentrations in adults with autism spectrum disorders.

The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY: Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders.

Reduced structural connectivity in the corpus callosum in patients with anorexia nervosa.

OBJECTIVE: Previous diffusion tensor imaging studies reported a reduced fractional anisotropy in the body of the corpus callosum in patients with anorexia nervosa, which may indicate impaired white matter integrity in interhemispheric connections. The aim of the current study was to investigate whether structural connectivity is affected in patients with anorexia nervosa. METHOD: To this end, we compared the number of streamlines (a model of the white matter fibre tracts) and the total volume filled by these streamlines in different subsections of the corpus callosum in 33 women with and 33 without anorexia nervosa as well as in 20 recovered individuals. RESULTS: The volume of streamlines in the anterior and mid-anterior subsection of the corpus callosum was reduced in women with, but not in those who had recovered from anorexia nervosa. No differences in number of streamlines was detected in the corpus callosum between patients with anorexia nervosa, healthy controls and recovered patients. CONCLUSIONS: Alterations of the corpus callosum have been repeatedly reported in anorexia nervosa. Since the recovered group did not differ from the healthy control group, the reported alterations in acute patients appear to represent a state and not a trait marker.

A new microsporidian parasite, Ordospora pajunii sp. nov (Ordosporidae), of Daphnia longispina highlights the value of genomic data for delineating species boundaries.

Speciation is a complex and continuous process that makes the delineation of species boundaries a challenging task in particular in species with little morphological differentiation, such as parasites. In this case, the use of genomic data is often necessary, such as for the intracellular Microsporidian parasites. Here, we characterize the genome of a gut parasite of the cladoceran Daphnia longispina (isolate FI-F-10), which we propose as a new species within the genus Ordospora: Ordospora pajunii sp. nov (Ordosporidae). FI-F-10 closest relative, Ordospora colligata is only found in D. magna. Both microsporidian species share several morphological features. Although it is not possible to estimate divergence times for Microsporidia due to the lack of fossil records and accelerated evolutionary rates, we base our proposal on the phylogenomic and genomic distances between both microsporidian lineages. The phylogenomic reconstruction shows that FI-F-10 forms an early diverging branch basal to the cluster that contains all known O. colligata strains. Whole-genome comparisons show that FI-F-10 presents a greater divergence at the sequence level than observed among O. colligata strains, and its genomic average nucleotide identity (ANI) values against O. colligata are beyond the intraspecific range previously established for yeast and prokaryotes. Our data confirm that the ANI metrics are useful for fine genetic divergence calibration across Microsporidia taxa. In combination with phylogenetic and ecological data, genome-based metrics provide a powerful approach to delimitate species boundaries.