ALBERT

Description: Background: Interactions between the orexin peptides and their cognate OX1 and OX2 receptors remain poorly characterized. Site-directed mutagenesis studies on orexin peptides and receptors have indicated amino acids important for ligand binding and receptor activation. However, a better understanding of specific pairwise interactions would benefit small molecule discovery. Results: We constructed a set of three-dimensional models of the orexin 1 receptor based on the 3D-structures of the orexin 2 receptor (released while this manuscript was under review), neurotensin receptor 1 and chemokine receptor CXCR4, conducted an exhaustive docking of orexin-A16–33 peptide fragment with ZDOCK and RDOCK, and analyzed a total of 4301 complexes through multidimensional scaling and clustering. The best docking poses reveal two alternative binding modes, where the C-terminus of the peptide lies deep in the binding pocket, on average about 5–6 Å above Tyr6.48 and close to Gln3.32. The binding modes differ in the about 100° rotation of the peptide; the peptide His26 faces either the receptor’s fifth transmembrane helix or the seventh helix. Both binding modes are well in line with previous mutation studies and partake in hydrogen bonding similar to suvorexant. Conclusions: We present two binding modes for orexin-A into orexin 1 receptor, which help rationalize previous results from site-directed mutagenesis studies. The binding modes should serve small molecule discovery, and offer insights into the mechanism of receptor activation.

Description: Association studies are an essential part of modern plant breeding, but are limited for polyploid crops. The increased number of possible genotype classes complicates the differentiation between them. Availabl...

Description: Eukaryotes display remarkable genome plasticity, which can include supernumerary chromosomes that differ markedly from the core chromosomes. Despite the widespread occurrence of supernumerary chromosomes in fu...

Description: Background: The mechanisms that underlie the diversification of tropical animals remain poorly understood, but new approaches that combine geo-spatial modeling with spatially explicit genetic data are providing fresh insights on this topic. Data about the diversification of tropical mammals remain particularly sparse, and vanishingly few opportunities exist to study endangered large mammals that increasingly exist only in isolated pockets. The chimpanzees of Cameroon represent a unique opportunity to examine the mechanisms that promote genetic differentiation in tropical mammals because the region is home to two chimpanzee subspecies: Pan troglodytes ellioti and P. t. trogolodytes. Their ranges converge in central Cameroon, which is a geographically, climatically and environmentally complex region that presents an unparalleled opportunity to examine the roles of rivers and/or environmental variation in influencing the evolution of chimpanzee populations. Results: We analyzed microsatellite genotypes and mtDNA HVRI sequencing data from wild chimpanzees sampled at a fine geographic scale across Cameroon and eastern Nigeria using a spatially explicit approach based upon Generalized Dissimilarity Modeling. Both the Sanaga River and environmental variation were found to contribute to driving separation of the subspecies. The importance of environmental variation differed among subspecies. Gene-environment associations were weak in P. t. troglodytes, whereas environmental variation was found to play a much larger role in shaping patterns of genetic differentiation in P. t. ellioti. Conclusions: We found that both the Sanaga River and environmental variation likely play a role in shaping patterns of chimpanzee genetic diversity. Future studies using single nucleotide polymorphism (SNP) data are necessary to further understand how rivers and environmental variation contribute to shaping patterns of genetic variation in chimpanzees.

Description: Background: Whereas the impact of endosymbionts on the ecology of their hosts is well known in some insect species, the question of whether host communities are influenced by endosymbionts remains largely unanswered. Notably, the coexistence of host species competing with each other, which is expected to be stabilized by their ecological differences, could be facilitated by differences in their endosymbionts. Yet, the composition of endosymbiotic communities housed by natural communities of competing host species is still almost unknown. In this study, we started filling this gap by describing and comparing the bacterial endosymbiotic communities of four sibling weevil species (Curculio spp.) that compete with each other to lay eggs into oak acorns (Quercus spp.) and exhibit marked ecological differences. Results: All four species housed the primary endosymbiont Candidatus Curculioniphilus buchneri, yet each of these had a clearly distinct community of secondary endosymbionts, including Rickettsia, Spiroplasma, and two Wolbachia strains. Notably, three weevil species harbored their own predominant facultative endosymbiont and possessed the remaining symbionts at a residual infection level. Conclusions: The four competing species clearly harbor distinct endosymbiotic communities. We discuss how such endosymbiotic communities could spread and keep distinct in the four insect species, and how these symbionts might affect the organization and species richness of host communities.

Description: Background: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant. Methods: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation. Results: The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Boger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipient-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts. Conclusions: Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.

Description: Background: Development of phylogenetic methods that do not rely on fossils for the study of evolutionary processes through time have revolutionized the eld of evolutionary biology and resulted in an unprecedented expansion of our knowledge about the tree of life. These methods have helped to shed light on the macroevolution of many taxonomic groups such as the placentals (Mammalia). However, despite the increase of studies addressing the diversication patterns of organisms, no synthesis has addressed the case of the most diversied mammalian clade: the Rodentia. Results: Here we present a rodent maximum likelihood phylogeny inferred from a molecular supermatrix. It is based on 11 mitochondrial and nuclear genes that covers 1,265 species, i.e., respectively 56 % and 81 % of the known specic and generic rodent diversity. The inferred topology recovered all Rodentia clades proposed by recent molecular works. A relaxed molecular clock dating approach provided a time framework for speciation events. We found that the Myomorpha clade shows a greater degree of variation in diversication rates than Sciuroidea, Caviomorpha, Castorimorpha and Anomaluromorpha. We identied a number of shifts in diversication rates within the major clades: two in Castorimorpha, three in Ctenohystrica, 6 within the squirrel-related clade and 24 in the Myomorpha clade. The majority of these shifts occurred within the most recent familial rodent radiations: the Cricetidae and Muridae clades. Using the topological imbalances and the time line we discuss the potential role of different diversication factors that might have shaped the rodents radiation. Conclusions: The present glimpse on the diversication pattern of rodents can be used for further comparative meta-analyses. Muroid lineages have a greater degree of variation in their diversication rates than any other 1rodent group. Different topological signatures suggest distinct diversication processes among rodent lineages. In particular, Muroidea and Sciuroidea display widespread distribution and have undergone evolutionary and adaptive radiation on most of the continents. Our results show that rodents experienced shifts in diversication rate regularly through the Tertiary, but at different periods for each clade. A comparison between the rodent fossil record and our results suggest that extinction led to the loss of diversication signal for most of the Paleogene nodes.

Description: Background: Crows and ravens (Passeriformes: Corvus) are large-brained birds with enhanced cognitiveabilities relative to other birds. They are among the few non-hominid organisms on Earth tobe considered intelligent and well-known examples exist of several crow species havingevolved innovative strategies and even use of tools in their search for food. The 40 Corvusspecies have also been successful dispersers and are distributed on most continents and inremote archipelagos. Results: This study presents the first molecular phylogeny including all species and a number ofsubspecies within the genus Corvus. We date the phylogeny and determine ancestral areas toinvestigate historical biogeographical patterns of the crows. Additionally, we use data onbrain size and a large database on innovative behaviour and tool use to test whether brain size(i) explains innovative behaviour and success in applying tools when foraging and (ii) hassome correlative role in the success of colonization of islands. Our results demonstrate thatcrows originated in the Palaearctic in the Miocene from where they dispersed to NorthAmerica and the Caribbean, Africa and Australasia. We find that relative brain size alonedoes not explain tool use, innovative feeding strategies and dispersal success within crows. Conclusions: Our study supports monophyly of the genus Corvus and further demonstrates the directionand timing of colonization from the area of origin in the Palaearctic to other continents andarchipelagos. The Caribbean was probably colonized from North America, although someNorth American ancestor may have gone extinct, and the Pacific was colonized multipletimes from Asia and Australia. We did not find a correlation between relative brain size, tooluse, innovative feeding strategies and dispersal success. Hence, we propose that all crows andravens have relatively large brains compared to other birds and thus the potential to beinnovative if conditions and circumstances are right.

Description: Background: Plants are sessile organisms that deal with their -sometimes adverse- environment in well-regulated ways. Chromatin remodeling involving SWI/SNF2-type ATPases is thought to be an important epigenetic mechanism for the regulation of gene expression in different developmental programs and for integrating these programs with the response to environmental signals. In this study, we report on the role of chromatin remodeling in Arabidopsis with respect to the variability of growth and gene expression in relationship to environmental conditions. Results: Already modest (2-fold) over-expression of the AtCHR23 ATPase gene in Arabidopsis results in overall reduced growth compared to the wild-type. Detailed analyses show that in the root, the reduction of growth is due to reduced cell elongation. The reduced-growth phenotype requires sufficient light and is magnified by applying deliberate abiotic (salt, osmotic) stress. In contrast, the knockout mutation of AtCHR23 does not lead to such visible phenotypic effects. In addition, we show that over-expression of AtCHR23 increases the variability of growth in populations of genetically identical plants. These data indicate that accurate and controlled expression of AtCHR23 contributes to the stability or robustness of growth. Detailed RNAseq analyses demonstrate that upon AtCHR23 over-expression also the variation of gene expression is increased in a subset of genes that associate with environmental stress. The larger variation of gene expression is confirmed in individual plants with the help of independent qRT-PCR analysis. Conclusions: Over-expression of AtCHR23 gives Arabidopsis a phenotype that is markedly different from the growth arrest phenotype observed upon over-expression of AtCHR12, the paralog of AtCHR23, in response to abiotic stress. This demonstrates functional sub-specialization of highly similar ATPases in Arabidopsis. Over-expression of AtCHR23 increases the variability of growth among genetically identical individuals in a way that is consistent with increased variability of expression of a distinct subset of genes that associate with environmental stress. We propose that ATCHR23-mediated chromatin remodeling is a potential component of a buffer system in plants that protects against environmentally-induced phenotypic and transcriptional variation.

Description: Background: Patellar luxation is an orthopedic disorder in which the patella moves out of its normal location within the femoral trochlea of the knee and it can lead to osteoarthritis, lameness, and pain. In dogs it is a heritable trait, with both environmental and genetic factors contributing to the phenotype. The prevalence of patellar luxation in the Dutch Flat-Coated Retriever population is 24%. In this study, we investigated the molecular genetics of the disorder in this population. Results: Genome-wide association analysis of 15,823 single nucleotide polymorphisms (SNPs) in 45 cases and 40 controls revealed that patellar luxation was significantly associated with a region on chromosome CFA07, and possibly with regions on CFA03, CFA31, and CFA36. The exons of the genes in these regions, 0,5 Mb combined, were analyzed further. These exons from 15 cases and a pooled sample from 15 controls were enriched using custom genomic hybridization arrays and analyzed by massive parallel DNA sequencing. In total 7257 variations were detected. Subsequently, a selection of 144 of these SNPs were genotyped in 95 Flat-Coated Retrievers. Nine SNPs, in eight genes on CFA07 and CFA31, were associated with patellar luxation (P