Lipid Binding Defects and Perturbed Synaptogenic Activity of a Collybistin R290H Mutant That Causes Epilepsy and Intellectual Disability

Signaling at nerve cell synapses is a key determinant of proper brain function, and synaptic defects—or synaptopathies—are at the basis of many neurological and psychiatric disorders. In key areas of the mammalian brain, such as the hippocampus or the basolateral amygdala, the clustering of the scaffolding protein Gephyrin and of γ-aminobutyric acid type A receptors at inhibitory neuronal synapses is critically dependent upon the brain-specific guanine nucleotide exchange factor Collybistin (Cb). Accordingly, it was discovered recently that an R290H missense mutation in the diffuse B-cell lymphoma homology domain of Cb, which carries the guanine nucleotide exchange factor activity, leads to epilepsy and intellectual disability in human patients. In the present study, we determined the mechanism by which the Cb^R290H mutation perturbs inhibitory synapse formation and causes brain dysfunction. Based on a combination of biochemical, cell biological, and molecular dynamics simulation approaches, we demonstrate that the R290H mutation alters the strength of intramolecular interactions between the diffuse B-cell lymphoma homology domain and the pleckstrin homology domain of Cb. This defect reduces the phosphatidylinositol 3-phosphate binding affinity of Cb, which limits its normal synaptogenic activity. Our data indicate that impairment of the membrane lipid binding activity of Cb and a consequent defect in inhibitory synapse maturation represent a likely molecular pathomechanism of epilepsy and mental retardation in humans.     

The evolution of intermediate castration virulence and ant coexistence in a spatially structured environment

Theory suggests that spatial structuring should select for intermediate levels of virulence in parasites, but empirical tests are rare and have never been conducted with castration (sterilizing) parasites. To test this theory in a natural landscape, we construct a spatially explicit model of the symbiosis between the ant-plant Cordia nodosa and its two, protecting ant symbionts, Allomerus and Azteca . Allomerus is also a castration parasite, preventing fruiting to increase colony fecundity. Limiting the dispersal of Allomerus and host plant selects for intermediate castration virulence. Increasing the frequency of the mutualist, Azteca , selects for higher castration virulence in Allomerus , because seeds from Azteca -inhabited plants are a public good that Allomerus exploits. These results are consistent with field observations and, to our knowledge, provide the first empirical evidence supporting the hypothesis that spatial structure can reduce castration virulence and the first such evidence in a natural landscape for either mortality or castration virulence.     

Can spatial sorting associated with spawning migration explain evolution of body size and vertebral number in Anguilla eels?

Spatial sorting is a process that can contribute to microevolutionary change by assembling phenotypes through space, owing to nonrandom dispersal. Here we first build upon and develop the “neutral” version of the spatial sorting hypothesis by arguing that in systems that are not characterized by repeated range expansions, the evolutionary effects of variation in dispersal capacity and assortative mating might not be independent of but interact with natural selection. In addition to generating assortative mating, variation in dispersal capacity together with spatial and temporal variation in quality of spawning area is likely to influence both reproductive success and survival of spawning migrating individuals, and this will contribute to the evolution of dispersal‐enhancing traits. Next, we use a comparative approach to examine whether differences in spawning migration distance among 18 species of freshwater Anguilla eels have evolved in tandem with two dispersal‐favoring traits. In our analyses, we use information on spawning migration distance, body length, and vertebral number that was obtained from the literature, and a published whole mitochondrial DNA‐based phylogeny. Results from comparative analysis of independent contrasts showed that macroevolutionary shifts in body length throughout the phylogeny have been associated with concomitant shifts in spawning migration. Shifts in migration distance were not associated with shifts in number of vertebrae. These findings are consistent with the hypothesis that spatial sorting has contributed to the evolution of more elongated bodies in species with longer spawning migration distances, or resulted in evolution of longer migration distances in species with larger body size. This novel demonstration is important in that it expands the list of ecological settings and hierarchical levels of biological organization for which the spatial sorting hypothesis seems to have predictive power.     

Reappraisal of early Miocene rails (Aves,Rallidae) from central France: diversity and character evolution

In Europe, Miocene rails (Aves, Rallidae) are quite abundant, but their phylogenetic placement in the context of recent forms has remained elusive. Rails from the early Miocene of the Saint‐Gérand‐le‐Puy area in central France were first described in the 19th century, and currently, only two species are recognized, namely Palaeoaramides christyi and Paraortygometra porzanoides. Our examination of the material however suggests the presence of four, likely coeval, species of rail from these deposits. Palaeoaramides eximius, previously synonymized with Palaeoaramides christyi, is here shown to probably be a distinct species, and a previously unrecognized rail, Baselrallus intermedius gen. et sp. nov., is described. To find out how these fossil rails are related to modern Rallidae, we compared them with an extensive sample of extant rails and identified plesiomorphic and derived features for crown group Rallidae. Our assessment does not support a particularly close relationship of either Palaeoaramides to Aramides or Paraortygometra to Crex (Ortygometra), and overall, these fossil rails are more primitive than previously assumed. Based on our observations of the morphology of the previously undescribed humerus of Palaeoaramides, we show this taxon to be outside crown group Rallidae, and perhaps closely related to the early Oligocene taxon Belgirallus. On the other hand, Paraortygometra porzanoides bears a resemblance to recent flufftails (Sarothrura spp.) in some elements, but whether it can be included in a clade together with flufftails is uncertain.     

Retinal Attachment Instability Is Diversified among Mammalian Melanopsins

Melanopsins play a key role in non-visual photoreception in mammals. Their close phylogenetic relationship to the photopigments in invertebrate visual cells suggests they have evolved to acquire molecular characteristics that are more suited for their non-visual functions. Here we set out to identify such characteristics by comparing the molecular properties of mammalian melanopsin to those of invertebrate melanopsin and visual pigment. Our data show that the Schiff base linking the chromophore retinal to the protein is more susceptive to spontaneous cleavage in mammalian melanopsins. We also find this stability is highly diversified between mammalian species, being particularly unstable for human melanopsin. Through mutagenesis analyses, we find that this diversified stability is mainly due to parallel amino acid substitutions in extracellular regions. We propose that the different stability of the retinal attachment in melanopsins may contribute to functional tuning of non-visual photoreception in mammals.     

Genetic variability and association of ISSR markers with some biochemical traits in mulberry (Morus spp.) genetic resources available in India

Utilizing intersimple sequence repeat (ISSR) markers, 18 mulberry (Morus spp.) germplasm collections were studied for genetic variability, phylogenetic relationship, and association with protein and sugar content. The genetic polymorphism exhibited by ISSR primers was 100%, and the genetic diversity recorded among the mulberry accessions had an average of 0.263 ± 0.094. Dendrogram (unweighted pair group method analysis) clustered the mulberry accessions into two major groups, one comprised the accessions collected from north or northeast regions of India, and the other comprised three subclusters and one isolate, i.e., Assamjati, a collection from Assam. Another subcluster contained accessions collected from Kerala, which belong to Morus indica. These accessions of M. indica from Kerala were found to be genetically diverse from north and northeast India. Multidimensional scaling of the ISSR data clearly separated the mulberry accessions according to their genetic diversity and protein content. Mulberry accessions were arbitrarily grouped into three classes viz. very low, moderate, and high in terms of protein and sugar content using standard statistical programs. Stepwise multiple regression analysis identified four ISSR markers (835_1,600, 835_5,600, 822_2,500, and 807_2,500) associated with protein content with highly positive correlation (p < 0.001) with linear curves with high F values (18.055 to 48.674; p < 0.001). In case of sugar content, four ISSR markers viz. 812₉₀₀, 817_1,500, 826_1,500, and 810_8,000 showed negative correlation. Hence, DNA markers for proteins seem promising and may be used in marker-assisted breeding program.