The CRHR1 gene,trauma exposure,and alcoholism risk: a test of G × E effects

The corticotropin‐releasing hormone type I receptor (CRHR1) gene has been implicated in the liability for neuropsychiatric disorders, particularly under conditions of stress. On the basis of the hypothesized effects of CRHR1 variation on stress reactivity, measures of adulthood traumatic stress exposure were analyzed for their interaction with CRHR1 haplotypes and single‐nucleotide polymorphisms (SNPs) in predicting the risk for alcoholism. Phenotypic data on 2533 non‐related Caucasian individuals (1167 alcoholics and 1366 controls) were culled from the publically available Study of Addiction: Genetics and Environment genome‐wide association study. Genotypes were available for 19 tag SNPs. Logistic regression models examined the interaction between CRHR1 haplotypes/SNPs and adulthood traumatic stress exposure in predicting alcoholism risk. Two haplotype blocks spanned CRHR1. Haplotype analyses identified one haplotype in the proximal block 1 (P = 0.029) and two haplotypes in the distal block 2 (P = 0.026, 0.042) that showed nominally significant (corrected P < 0.025) genotype × traumatic stress interactive effects on the likelihood of developing alcoholism. The block 1 haplotype effect was driven by SNPs rs110402 (P = 0.019) and rs242924 (P = 0.019). In block 2, rs17689966 (P = 0.018) showed significant and rs173365 (P = 0.026) showed nominally significant, gene × environment (G × E) effects on alcoholism status. This study extends the literature on the interplay between CRHR1 variation and alcoholism, in the context of exposure to traumatic stress. These findings are consistent with the hypothesized role of the extra hypothalamic corticotropin‐releasing factor system dysregulation in the initiation and maintenance of alcoholism. Molecular and experimental studies are needed to more fully understand the mechanisms of risk and protection conferred by genetic variation at the identified loci .     

Genetic architecture of subcortical brain regions: common and region‐specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N = 1038; mean age = 21.6 ± 3.2 years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region‐specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region.     

Cortistatin radioligand binding in wild-type and somatostatin receptor-deficient mouse brain

Cortistatin-14 (CST-14) is a recently discovered member of the somatostatin family of neuropeptides. It shares 11 of its 14 amino acids with somatostatin-14 (SRIF-14). In the present study, binding sites for cortistatin-14 in the mouse brain were examined and compared to those for somatostatin using iodinated cortistatin-14 and iodinated somatostatin-14. By in vitro receptor autoradiography, high densities of cortistatin-14 and somatostatin-14 specific binding sites were detected in the cortex, hippocampal formation, basolateral amygdala and medial habenula. Unlabeled 100 nM cortistatin-14 inhibited iodinated somatostatin-14 binding in the hippocampus, but not in the cortex or amygdaloid nuclei. In somatostatin receptor subtype-2 knock-out (KO) mice, autoradiographic iodinated somatostatin-14 binding was observed in the hippocampus and habenula but was removed in the cortex and amygdaloid nuclei, specific iodinated cortistatin-14 binding sites were found in the hippocampus, habenula and throughout the cortex. We conclude that the somatostatin receptor subtype-2 is responsible for somatostatin binding in cortical and amygdaloid regions and that cortistatin predominantly interacts with the same receptors as somatostatin.     

Host plant and competitor identity matter in genotype × genotype × environment interactions between vetch and pea aphids

1. Selection does not only operate in a genotype (G) × environment (E) context, but can also be modulated by the activities of organisms interacting with their environment (G × G × E). 2. The influences of aphid clonal identity and host plant (Vicia faba) intraspecific genetic variation on the performance of five genotypes of pea aphid (Acyrthosiphon pisum) were investigated – with and without interaction with a competing heterospecific clone of vetch aphid (Megoura viciae) – across three cultivars of V. faba. 3. Pea aphid performance in the presence of a competing vetch aphid clone (G × G × E) compared with the absence of competition (G × E) revealed strong context‐dependent, genotype‐specific shifts in performance, influenced by plant cultivar, competitor presence and their interaction. 4. The performance of vetch aphid in competition with each pea aphid clone was also compared. Here, competitor's genotype and abundance underlay a remarkably varied response by vetch aphid across interactions. 5. The study shows that aphid genotypes exhibit a varying degree of risk spreading, contingent on competitor identity and the patterns of aggregation across three plant cultivars. Owing to feedback loops between species activities and selective forces acting on them, our findings suggest that there are context‐dependent responses by competitors that are shaped via the interplay of the co‐occurring species and their biotic environment. 6. This work highlights the complexity of species interactions and the importance of investigating reciprocity between competition and intraspecific genetic variation. A better understanding of the eco‐evolutionary interactions between phloem‐feeding insects and their host plants can potentially be used to enhance crop protection and pest control.     

Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees

Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss‐of‐function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non‐synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1‐weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.     

Genotype × environment interaction in the allometry of body,genitalia and signal traits in Enchenopa treehoppers (Hemiptera: Membracidae)

Developmental plasticity may promote divergence by exposing genetic variation to selection in novel ways in new environments. We tested for this effect in the static allometry (i.e. scaling on body size) of traits in advertisement signals, body and genitalia. We used a member of the Enchenopa binotata species complex of treehoppers – a clade of plant‐feeding insects in which speciation is associated with colonization of novel environments involving marked divergence in signals, subtle divergence in body size and shape, and no apparent divergence in genitalia. We found no change in mean allometric slopes across environments, but substantial genetic variation and genotype × environment interaction (G × E) in allometry. The allometry of signal traits showed the most genetic variation and G × E, and that of genitalia showed the weakest G × E. Our findings suggest that colonizing novel environments may have stronger diversifying consequences for signal allometry than for genitalia allometry. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 187–196.     

Inducible and neuron-specific gene expression in the adult mouse brain with the rtTA2S-M2 system

To achieve inducible and reversible gene expression in the adult mouse brain, we exploited an improved version of the tetracycline-controlled transactivator-based system (rtTA2(S)-M2, rtTA2 hereafter) and combined it with the forebrain-specific CaMKIIalpha promoter. Several independent lines of transgenic mice carrying the CaMKIIalpha promoter-rtTA2 gene were generated and examined for anatomical profile, doxycycline (dox)-dependence, time course, and reversibility of gene expression using several lacZ reporter lines. In two independent rtTA2-expressing lines, dox-treatment in the diet induced lacZ reporter expression in neurons of several forebrain structures including cortex, striatum, hippocampus, amygdala, and olfactory bulb. Gene expression was dose-dependent and was fully reversible. Further, a similar pattern of expression was obtained in three independent reporter lines, indicating the consistency of gene expression. Transgene expression could also be activated in the developing brain (P0) by dox-treatment of gestating females. These new rtTA2-expressing mice allowing inducible and reversible gene expression in the adult or developing forebrain represent useful models for future genetic studies of brain functions.     

Ample genetic variation but no evidence for genotype specificity in an all‐parthenogenetic host–parasitoid interaction

Antagonistic coevolution between hosts and parasites can result in negative frequency‐dependent selection and may thus be an important mechanism maintaining genetic variation in populations. Negative frequency‐dependence emerges readily if interactions between hosts and parasites are genotype‐specific such that no host genotype is most resistant to all parasite genotypes, and no parasite genotype is most infective on all hosts. Although there is increasing evidence for genotype specificity in interactions between hosts and pathogens or microparasites, the picture is less clear for insect host–parasitoid interactions. Here, we addressed this question in the black bean aphid (Aphis fabae) and its most important parasitoid Lysiphlebus fabarum. Because both antagonists are capable of parthenogenetic reproduction, this system allows for powerful tests of genotype × genotype interactions. Our test consisted of exposing multiple host clones to different parthenogenetic lines of parasitoids in all combinations, and this experiment was repeated with animals from four different sites. All aphids were free of endosymbiotic bacteria known to increase resistance to parasitoids. We observed ample genetic variation for host resistance and parasitoid infectivity, but there was no significant host clone × parasitoid line interaction, and this result was consistent across the four sites. Thus, there is no evidence for genotype specificity in the interaction between A. fabae and L. fabarum, suggesting that the observed variation is based on rather general mechanisms of defence and attack.     

Low genetic variation of invasive Fallopia spp. in their northernmost European distribution range

Knowledge about the reproduction strategies of invasive species is fundamental for effective control. The invasive Fallopia taxa (Japanese knotweed s.l.) reproduce mainly clonally in Europe, and preventing spread of vegetative fragments is the most important control measure. However, high levels of genetic variation within the hybrid F. × bohemica indicate that hybridization and seed dispersal could be important. In Norway in northern Europe, it is assumed that these taxa do not reproduce sexually due to low temperatures in the autumn when the plants are flowering. The main objective of this study was to examine the genetic variation of invasive Fallopia taxa in selected areas in Norway in order to evaluate whether the taxa may reproduce by seeds in their most northerly distribution range in Europe. Fallopia stands from different localities in Norway were analyzed with respect to prevalence of taxa, and genetic variation within and between taxa was studied using amplified fragment length polymorphism (AFLP). Taxonomic identification based on morphology corresponded with identification based on simple sequence repeats (SSR) and DNA ploidy levels (8× F. japonica, 6× F. × bohemica and 4× F. sachalinensis). No genetic variation within F. japonica was detected. All F. × bohemica samples belonged to a single AFLP genotype, but one sample had a different SSR genotype. Two SSR genotypes of F. sachalinensis were also detected. Extremely low genetic variation within the invasive Fallopia taxa indicates that these taxa do not reproduce sexually in the region, suggesting that control efforts can be focused on preventing clonal spread. Climate warming may increase sexual reproduction of invasive Fallopia taxa in northern regions. The hermaphrodite F. × bohemica is a potential pollen source for the male‐sterile parental species. Targeted eradication of the hybrid can therefore reduce the risk of increased sexual reproduction under future warmer climate.     

Within‐ and among‐population variation in infectivity,latency and spore production in a host–pathogen system

In spatially structured populations, host–parasite coevolutionary potential depends on the distribution of genetic variation within and among populations. Inoculation experiments using the plant, Silene latifolia, and its fungal pathogen, Microbotryum violaceum, revealed little overall differentiation in infectivity/resistance, latency or spore production among host or pathogen populations. Within populations, fungal strains had similar means, but varied in performance across plant populations. Variation in resistance among seed families indicates the potential for parasite‐mediated selection, whereas there was little evidence for local pathogen genotype × plant genotype interactions assumed by most theoretical coevolution models. Lower spore production on sympatric than allopatric hosts confirmed local fungal maladaptation already observed for infectivity. Correlations between infectivity and latency or spore production suggest a common mechanism for variation in these traits. Our results suggest low variation available to this pathogen for tracking its coevolving host. This may be caused by random drift, breeding system or migration characteristic of metapopulation dynamics.     

Influence of genotype and geography on shell shape and morphometric trait variation among North Atlantic blue mussel (Mytilus spp.) populations

The influence of geography and genotype on shell shape (outline) and trait (morphometric) variation among North Atlantic blue mussels and their hybrids has been examined. Shape differences among reference taxa (Mytilus trossulus, Mytilus edulis and Mytilus galloprovincialis) were consistent with an association between taxon‐specific genes and shape genes. Newfoundland M. edulis × M. trossulus populations and northern Quebec M. trossulus populations exhibited an uncoupling of taxon‐specific genes from shape genes, whereas Nova Scotia M. trossulus populations and SW England M. edulis × M. galloprovincialis populations exhibited an association between taxon‐specific genes and shape genes. We found no evidence of a geographic effect (NE versus NW Atlantic) for shape variation, indicating that the genotype effect is stronger than any geographic effect at macrogeographic scales. Pronounced differences were observed in trait variability consistent with an association between taxon‐specific genes and trait genes in European populations, and trait divergence of New York M. edulis from all European mussels. Trait variability in mussels from Newfoundland, Nova Scotia and northern Quebec indicated an uncoupling of taxon genes from trait genes, whereas trait variability in SW England M. edulis × M. galloprovincialis populations was consistent with background genotype, indicating a strong association between taxon genes and trait genes. A pronounced macrogeographic split (NE versus NW Atlantic) regardless of taxonomy was observed, indicating that geography exerts a greater influence than genotype on trait variation at the macrogeographic scale. This is consistent with pronounced within‐taxon genetic divergence, indicative of different selection regimes or more likely of different evolutionary histories of mussels on either side of the North Atlantic. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 96 , 875–897.     

Genetic by environment interactions affect plant–soil linkages

The role of plant intraspecific variation in plant–soil linkages is poorly understood, especially in the context of natural environmental variation, but has important implications in evolutionary ecology. We utilized three 18‐ to 21‐year‐old common gardens across an elevational gradient, planted with replicates of five Populus angustifolia genotypes each, to address the hypothesis that tree genotype (G), environment (E), and G × E interactions would affect soil carbon and nitrogen dynamics beneath individual trees. We found that soil nitrogen and carbon varied by over 50% and 62%, respectively, across all common garden environments. We found that plant leaf litter (but not root) traits vary by genotype and environment while soil nutrient pools demonstrated genotype, environment, and sometimes G × E interactions, while process rates (net N mineralization and net nitrification) demonstrated G × E interactions. Plasticity in tree growth and litter chemistry was significantly related to the variation in soil nutrient pools and processes across environments, reflecting tight plant–soil linkages. These data overall suggest that plant genetic variation can have differential affects on carbon storage and nitrogen cycling, with implications for understanding the role of genetic variation in plant–soil feedback as well as management plans for conservation and restoration of forest habitats with a changing climate.     

Reaction norms of Arabidopsis. I. Plasticity of characters and correlations across water,nutrient and light gradients

The univariate and multivariate study of variation for phenotypic plasticity is central to providing a clear understanding of hypotheses about the genetic control and evolution of reaction norms in natural populations. Arabidopsis thaliana is an ideal organism for the study of Genotype × Environment interactions (i.e., genetic variation for plasticity), because of the ease with which it can be grown in large numbers and due to the amount of information already available on its genetics, physiology and developmental biology. In this paper, we report on the plasticity, genetic variation and G × E interactions of four populations of A. thaliana in response to three environmental gradients (water, light and nutrients), each characterized by four levels of the controlled parameter. We measured nine traits and obtained their reaction norms. Path analysis was used to study the plasticity of character correlations. We found a tendency for A. thaliana reaction norms to be linear (either flat, i.e. no plasticity, or with a significant slope), in accordance with previous studies. We detected substantial amounts of genetic variation for plasticity in the light and nutrient gradients, but not in the water gradient. Dramatic restructuring of character correlations was induced by changes in environmental conditions, although some paths tended to be stable irrespective of the environment, thereby suggesting some degree of canalization.     

VIP in the rat brain: Evidence for a major pathway linking the amygdala and hypothalamus via the stria terminalis

Summary We report here on the detailed distribution of VIP-like immuno-reactivity in the rat brain by a combined immunological approach using immunocytochemistry and radioimmunoassay. VIP-like immunoreactivity was widely distributed. Cell bodies and fibres were noted principally in the cortex, hippocampus, amygdala, suprachiasmatic nucleus and brain stem. In addition dense areas of immunoreactive fibres and terminals were seen in the stria terminalis and its bed nucleus. The fibres appear to form a major VIP-containing pathway which links the amygdaloid complex with the hypothalamus. Although the functional significance of VIP in the brain is unknown, its presence in the amygdala, the hypothalamus and their linking pathway, as well as its pharmacological actions suggest that is may play a role in neuroendocrine regulation and the modulation of hypothalamic function.     

Amygdala kindled seizure stage is related to altered benzodiazepine binding site density

Benzodiazepine receptor binding was examined in rats at 3 stages of amygdaloid kindling (i.e., initial afterdischarge, Stage 3 and Stage 5) immediately or 24 hr after seizure. 3H-diazepam binding site density (Bmax) was significantly increased 24 hr after Stage 3 and Stage 5 kindled seizures in the hippocampus but not in the amygdala. There were no significant differences in the dissociation constants (KD) between kindled and control rats at any time point examined for either brain region. These results demonstrate that changes in benzodiazepine binding are observed with partial kindled seizures (i.e., Stage 3), indicating that generalized seizures are not prerequisite to increased benzodiazepine receptor site density.     

The effects of selection,drift and genetic variation on life‐history trait divergence among insular populations of natterjack toad,Bufo calamita

Although loss of genetic variation is frequently assumed to be associated with loss of adaptive potential, only few studies have examined adaptation in populations with little genetic variation. On the Swedish west coast, the northern fringe populations of the natterjack toad Bufo calamita inhabit an atypical habitat consisting of offshore rock islands. There are strong among‐population differences in the amount of neutral genetic variation, making this system suitable for studies on mechanisms of trait divergence along a gradient of within‐population genetic variation. In this study, we examined the mechanisms of population divergence using Q_ST–F_ST comparisons and correlations between quantitative and neutral genetic variation. Our results suggest drift or weak stabilizing selection across the six populations included in this study, as indicated by low Q_ST–F_ST values, lack of significant population × temperature interactions and lack of significant differences among the islands in breeding pond size. The six populations included in this study differed in both neutral and quantitative genetic variation. Also, the correlations between neutral and quantitative genetic variation tended to be positive, however, the relatively small number of populations prevents any strong conclusions based on these correlations. Contrary to the majority of Q_ST–F_ST comparisons, our results suggest drift or weak stabilizing selection across the examined populations. Furthermore, the low heritability of fitness‐related traits may limit evolutionary responses in some of the populations.     

Genetic specificity and potential for local adaptation between dengue viruses and mosquito vectors

Background  

Several observations support the hypothesis that vector-driven selection plays an important role in shaping dengue virus (DENV) genetic diversity. Clustering of DENV genetic diversity at a particular location may reflect underlying genetic structure of vector populations, which combined with specific vector genotype × virus genotype (G × G) interactions may promote adaptation of viral lineages to local mosquito vector genotypes. Although spatial structure of vector polymorphism at neutral genetic loci is well-documented, existence of G × G interactions between mosquito and virus genotypes has not been formally demonstrated in natural populations. Here we measure G × G interactions in a system representative of a natural situation in Thailand by challenging three isofemale families from field-derived Aedes aegypti with three contemporaneous low-passage isolates of DENV-1.