The significance of sexual reproduction for local adaptation in Taraxacum

One of the aspects of sexual reproduction, such as is practised by most eukaryote, multicellular organisms, is that each offspring receives a random selection of alleles from its father and its mother. This way, existing genotypes are broken up and new ones are created in every generation. As each environment varies in time and space, to survive, species need to find ways for continuously matching their genotype to the changing conditions. It has often been assumed and modelled that, because of this continuous reshuffling of alleles, sexual organisms will adapt to their environment in different ways than do sexually reproducing organisms. Dandelions (Taraxacum) form an agamic complex with sexual, diploid genotypes and asexual (mainly) triploid genotypes. In many cases sexuals and apomicts occur in the same field. This makes dandelions a convenient species to study differences in adaptation between the two models of reproduction, though the difference in ploidy level complicates the picture. This thesis describes patterns of genotypic and phenotypic variation among and between sexual and apomictic Taraxacum under various environmental conditions. Based on existing models and models developed in this thesis, a theory is presented about the significance of sexuality for Taraxacum

Exploration of large, rare copy number variants associated with psychiatric and neurodevelopmental disorders in individuals with anorexia nervosa

Anorexia nervosa (AN) is a serious and heritable psychiatric disorder. To date, studies of copy number variants (CNVs) have been limited and inconclusive because of small sample sizes. We conducted a case-only genome-wide CNV survey in 1983 female AN cases included in the Genetic Consortium for Anorexia Nervosa. Following stringent quality control procedures, we investigated whether pathogenic CNVs in regions previously implicated in psychiatric and neurodevelopmental disorders were present in AN cases. We observed two instances of the well-established pathogenic CNVs in AN cases. In addition, one case had a deletion in the 13q12 region, overlapping with a deletion reported previously in two AN cases. As a secondary aim, we also examined our sample for CNVs over 1 Mbp in size. Out of the 40 instances of such large CNVs that were not implicated previously for AN or neuropsychiatric phenotypes, two of them contained genes with previous neuropsychiatric associations, and only five of them had no associated reports in public CNV databases. Although ours is the largest study of its kind in AN, larger datasets are needed to comprehensively assess the role of CNVs in the etiology of AN

Identification of Srp9 as a febrile seizure susceptibility gene

Objective: Febrile seizures (FS) are the most common seizure type in young children. Complex FS are a risk factor for mesial temporal lobe epilepsy (mTLE). To identify new FS susceptibility genes we used a forward genetic strategy in mice and subsequently analyzed candidate genes in humans. Methods: We mapped a quantitative trait locus (QTL1) for hyperthermia-induced FS on mouse chromosome 1, containing the signal recognition particle 9 (Srp9) gene. Effects of differential Srp9 expression were assessed in vivo and in vitro. Hippocampal SRP9 expression and genetic association were analyzed in FS and mTLE patients. Results: Srp9 was differentially expressed between parental strains C57BL/6J and A/J. Chromosome substitution strain 1 (CSS1) mice exhibited lower FS susceptibility and Srp9 expression than C57BL/6J mice. In vivo knockdown of brain Srp9 reduced FS susceptibility. Mice with reduced Srp9 expression and FS susceptibility, exhibited reduced hippocampal AMPA and NMDA currents. Downregulation of neuronal Srp9 reduced surface expression of AMPA receptor subunit GluA1. mTLE patients with antecedent FS had higher SRP9 expression than patients without. SRP9 promoter SNP rs12403575(G/A) was genetically associated with FS and mTLE. Interpretation: Our findings identify SRP9 as a novel FS susceptibility gene and indicate that SRP9 conveys its effects through endoplasmic reticulum (ER)-dependent synthesis and trafficking of membrane proteins, such as glutamate receptors. Discovery of this new FS gene and mechanism may provide new leads for early diagnosis and treatment of children with complex FS at risk for mTLE

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Spatial arrangement of Phyteuma nigrum and insect visitation

How distances between plants and inflorescences of Phyteuma nigrum affect pollinator behaviour was examined in a natural situation as well as experimentally. Patches of Phyteuma in two densities were set up in a field in Drenthe. In the natural population flight distances of bumblebees and syrphids were examined. Migration of pollinators was demonstrated between two populations of Phyteuma, which in previous studies had seemed completely isolated. The largest distance between recaptures of bumblebees on Phyteuma on the same day was 200 m. In the experimental patches bumblebees made longer foraging bouts in high-density patches than in low-density patches. They stayed longer per inflorescence and visited more inflorescences per plant in low density, while the number of inflorescences visited per minute did not differ between densities. In low density bumblebees flew more often to nearest neighbours and visited more inflorescences per plant. Plants with four inflorescences were preferred to plants with one in both densities, and the preference was stronger in low density. Implications for the fitness of the plants are discussed.

The canonical equation of adaptive dynamics for Mendelian diploids and haplo-diploids

One of the powerful tools of adaptive dynamics is its so-called canonical equation (CE), a differential equation describing how the prevailing trait vector changes over evolutionary time. The derivation of the CE is based on two simplifying assumptions, separation of population dynamical and mutational time scales and small mutational steps. (It may appear that these two conditions rarely go together. However, for small step sizes the time-scale separation need not be very strict.) The CE was derived in 1996, with mathematical rigour being added in 2003. Both papers consider only well-mixed clonal populations with the simplest possible life histories. In 2008, the CE's reach was heuristically extended to locally well-mixed populations with general life histories. We, again heuristically, extend it further to Mendelian diploids and haplo-diploids. Away from strict time-scale separation the CE does an even better approximation job in the Mendelian than in the clonal case owing to gene substitutions occurring effectively in parallel, which obviates slowing down by clonal interference

Model Analysis of the effects of historic CO2 levels and nitrogen inputs on vegetation succession

Simulation models are useful to analyze and predict the effects of changes in atmospheric CO2 concentration and N deposition on terrestrial ecosystems. The effects of such abiotic changes on ecosystem variables such as nitrogen mineralization and carbon accumulation can affect plant species composition, which in turn may affect various ecosystem processes. However, these interacting effects of plant species composition on ecosystem processes and vice versa are often not included in simulation models. In this paper, a model is developed that includes both plant competition and the flows of nutrients, carbon, and water through the ecosystem. Direct effects of changing atmospheric CO2 on biomass, plant nitrogen concentrations, and litter quantity and quality are simulated together with indirect effects through changes in plant species composition. This model is validated against data from a primary succession chronosequence sere of Dutch inland dunes. For this validation, historical N deposition and atmospheric CO2 concentration records are used. Simulated plant species biomass, organic matter C and N, and total C and N accumulation were found to correspond to measured data. The model simulated plant species replacement well at the different sites of the chronosequence even though the historic conditions differed much between the sites. Additional analyses of the effect of N deposition (preindustrial to present-day) and elevated CO2 (preindustrial to present-day) in this ecosystem showed that N deposition had a strong effect both on vegetation development and on C and N accumulation. Compared to this, the stimulating effects of elevated CO2 on vegetation development were relatively small. Elevated CO2 affected early vegetation development, but the long-term response of vegetation development is dependent on N availability. In old mature forest, N deposition had only small effects while elevated CO2 delayed forest aging. Indirect effects of CO2 on C and N accumulation through changing plant competitive relations may ultimately be larger than direct CO2 effects

Carbon and nitrogen in soil and vegetation at sites differing in successional age

We studied vegetation and soil development during primary succession in an inland drift sand area in the Netherlands. We compared five sites at which primary succession had started at different moments in the past, respectively 0, 10, 43 and 121 years ago, and a site at which succession had not yet started. In the three younger sites the vegetation was herbaceous, whereas in the two older sites a pine forest had formed. Forest formation was accompanied by the development of an FH-layer in the soil, an increase in the amount of soil organic matter, and an increase in nitrogen mineralisation rate from 1.9 to 18 g N m–2 yr–1. Soil moisture content also increased, whereas pH showed a steady decrease with site age. The vegetation changed from a herbaceous vegetation dominated by mosses and lichens and the grass species Corynephorus canescens and Festuca ovina towards a pine forest with an understorey vegetation dominated by Deschampsia flexuosa and, at the oldest site, with dwarf shrubs Empetrum nigrum and Vaccinium myrtillus. At the same time the total amounts of carbon and nitrogen of the ecosystem increased, with a relatively stronger increase of the carbon pool. The establishment of trees during succession greatly affects the dynamics of the ecosystem, especially its carbon dynamics