Clathrin light chains contain brain-specific insertion sequences and a region of homology with intermediate filaments

The primary structures of four bovine clathrin light chains have been determined. Light chains LCa and LCb are homologous proteins encoded by different genes. In the brain the messenger RNA from these genes undergoes differential splicing to yield proteins having centrally inserted brain-specific sequences. A potentially alpha-helical region of the clathrin light chains shows homology with intermediate filament proteins.     

Spatial scaling of microbial eukaryote diversity

Patterns in the spatial distribution of organisms provide important information about mechanisms that regulate the diversity of life and the complexity of ecosystems. Although microorganisms may comprise much of the Earth's biodiversity and have critical roles in biogeochemistry and ecosystem functioning, little is known about their spatial diversification. Here we present quantitative estimates of microbial community turnover at local and regional scales using the largest spatially explicit microbial diversity data set available (> 10(6) sample pairs). Turnover rates were small across large geographical distances, of similar magnitude when measured within distinct habitats, and did not increase going from one vegetation type to another. The taxa-area relationship of these terrestrial microbial eukaryotes was relatively flat (slope z = 0.074) and consistent with those reported in aquatic habitats. This suggests that despite high local diversity, microorganisms may have only moderate regional diversity. We show how turnover patterns can be used to project taxa-area relationships up to whole continents. Taxa dissimilarities across continents and between them would strengthen these projections. Such data do not yet exist, but would be feasible to collect.     

Synopsis and taxonomic revision of three genera in the snake tribe Sonorini

ABSTRACT

Delimiting species is a crucial goal of integrative biology, and yet can be misled by homoplasy and high levels of morphological variation. The snake tribe Sonorini contains three genera that have long confounded taxonomists: Chilomeniscus, Chionactis and Sonora. Dynamic colour evolution in this group, including rampant geographic variation in colour and colour polymorphism, has led to a chaotic taxonomy. We used mitochondrial and high-throughput nuclear data (ddRADseq) and complete taxonomic sampling of each genus to reconstruct phylogenetic relationships and systematically revise the genus. Our research revealed that Sonora is paraphyletic with regards to Chilomeniscus and Chionactis and that at least one species (S. semiannulata) is paraphyletic with respect to at least one other recognized species. Additionally, we found substantial undescribed genetic diversity within multiple species which is incongruent with morphological variation in coloration. Accordingly, we proposed synonymizing Chionactis and Chilomeniscus with Sonora, which has taxonomic priority over both genera. As we found genetic evidence that supported some of the historically delimited diversity within multiple taxa, we revised species-level taxonomy accordingly. This new taxonomy recognizes a revised genus of Sonora that contains 15 species of diminutive and often brightly coloured snakes that are distributed from central Mexico to north-western USA.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:45A553D8-6435-4E0A-84ED-DF31E2CCD872     

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10?? to P = 1.8 × 10???) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10?3 to P = 1.2 × 10?13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.     

IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics

Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequently found in human glioblastomas and cytogenetically normal acute myeloid leukaemias (AML). These alterations are gain-of-function mutations in that they drive the synthesis of the ‘oncometabolite’ R-2-hydroxyglutarate (2HG). It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukaemogenesis. Here we report the characterization of conditional knock-in (KI) mice in which the most common IDH1 mutation, IDH1(R132H), is inserted into the endogenous murine Idh1 locus and is expressed in all haematopoietic cells (Vav-KI mice) or specifically in cells of the myeloid lineage (LysM-KI mice). These mutants show increased numbers of early haematopoietic progenitors and develop splenomegaly and anaemia with extramedullary haematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells have hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1- or IDH2-mutant AML. To our knowledge, our study is the first to describe the generation and characterization of conditional IDH1(R132H)-KI mice, and also the first report to demonstrate the induction of a leukaemic DNA methylation signature in a mouse model. Our report thus sheds light on the mechanistic links between IDH1 mutation and human AML.     

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).