Revised Annotations, Sex-Biased Expression, and Lineage-Specific Genes in the Drosophila melanogaster group

Here, we provide revised gene models for D. ananassae, D. yakuba, and D. simulans, which include UTRs and empirically verified intron-exon boundaries, as well as ortholog groups identified using a fuzzy reciprocal-best-hit blast comparison. Using these revised annotations, we perform differential expression testing using the cufflinks suite to provide a broad overview of differential expression between reproductive tissues and the carcass. We identify thousands of genes that are differentially expressed across tissues in D. yakuba and D. simulans, with roughly 60% agreement in expression patterns of orthologs in D. yakuba and D. simulans. We identify several cases of putative polycistronic transcripts, pointing to a combination of transcriptional read-through in the genome as well as putative gene fusion and fission events across taxa. We furthermore identify hundreds of lineage specific genes in each species with no blast hits among transcripts of any other Drosophila species, which are candidates for neofunctionalized proteins and a potential source of genetic novelty.Comment: Revised manuscript, also available online preprint at G3: Genes, Genomes, Genetics. Gene models, ortholog calls, and tissue specific expression results are available at http://github.com/ThorntonLab/GFF or the UCSC browser on the Thornton Lab public track hub at http://genome.ucsc.ed

Genetics of Intraspecies Variation in Avoidance Behavior Induced by a Thermal Stimulus in Caenorhabditis elegans.

Individuals within a species vary in their responses to a wide range of stimuli, partly as a result of differences in their genetic makeup. Relatively little is known about the genetic and neuronal mechanisms contributing to diversity of behavior in natural populations. By studying intraspecies variation in innate avoidance behavior to thermal stimuli in the nematode Caenorhabditis elegans, we uncovered genetic principles of how different components of a behavioral response can be altered in nature to generate behavioral diversity. Using a thermal pulse assay, we uncovered heritable variation in responses to a transient temperature increase. Quantitative trait locus mapping revealed that separate components of this response were controlled by distinct genomic loci. The loci we identified contributed to variation in components of thermal pulse avoidance behavior in an additive fashion. Our results show that the escape behavior induced by thermal stimuli is composed of simpler behavioral components that are influenced by at least six distinct genetic loci. The loci that decouple components of the escape behavior reveal a genetic system that allows independent modification of behavioral parameters. Our work sets the foundation for future studies of evolution of innate behaviors at the molecular and neuronal level

Standard and generalized McDonald–Kreitman test: a website to detect selection by comparing different classes of DNA sites

The McDonald and Kreitman test (MKT) is one of the most powerful and extensively used tests to detect the signature of natural selection at the molecular level. Here, we present the standard and generalized MKT website, a novel website that allows performing MKTs not only for synonymous and nonsynonymous changes, as the test was initially described, but also for other classes of regions and/or several loci. The website has three different interfaces: (i) the standard MKT, where users can analyze several types of sites in a coding region, (ii) the advanced MKT, where users can compare two closely linked regions in the genome that can be either coding or noncoding, and (iii) the multi-locus MKT, where users can analyze many separate loci in a single multi-locus test. The website has already been used to show that selection efficiency is positively correlated with effective population size in the Drosophila genus and it has been applied to include estimates of selection in DPDB. This website is a timely resource, which will presumably be widely used by researchers in the field and will contribute to enlarge the catalogue of cases of adaptive evolution. It is available at http://mkt.uab.es

Engineering & Performance of DuoTurbo: Microturbine with Counter-Rotating Runners

Considering the nuclear phase-out strategy of several European countries and the future tendency to promote renewable energies, the exploitation of small hydropower sites (<10 MW) becomes increasingly important. In this framework DuoTurbo Turbine, a new DuoTurbo-microturbine prototype for drinking water networks has been jointly developed by the HES-SO Valais//Wallis , the EPFL-Laboratory for Hydraulic Machines and industrial partners. The modular in- line “plug & play” technology requires low investment, reaching economic feasibility with an available power between 5 kW and 25 kW. One stage of the microturbine consists of two axial counter-rotating runners that form a compact independent unit. Each runner of the turbine holds its own rim generator, the DuoTurbo-configuration involving that each hydraulic runner is integral with each electrical rotor. The possibility of stacking several stages in series enables covering quite a wide range of hydraulic power and, thus, recovering a maximum of energy dissipated in release valves of water supply systems. The present work introduces the global concept of the implemented prototype of the DuoTurbo-microturbine, to target a maxim al injected power of 5 kW for a discharge of 9 l/ s and a head of 24.5 m per stage. The main features of the hydraulic, the mechanical, the electrical and the electronic design are presented. The hydraulic performance is, then, assessed using CFD simulations for the expected operating range. Finally, the performance measurements of the single-stage prototype installed in the hydraulic test rig of the HES-SO Valais//Wallis are presented

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Genomic signatures of population decline in the malaria mosquito Anopheles gambiae

Population genomic features such as nucleotide diversity and linkage disequilibrium are expected to be strongly shaped by changes in population size, and might therefore be useful for monitoring the success of a control campaign. In the Kilifi district of Kenya, there has been a marked decline in the abundance of the malaria vector Anopheles gambiae subsequent to the rollout of insecticide-treated bed nets. To investigate whether this decline left a detectable population genomic signature, simulations were performed to compare the effect of population crashes on nucleotide diversity, Tajima's D, and linkage disequilibrium (as measured by the population recombination parameter ρ). Linkage disequilibrium and ρ were estimated for An. gambiae from Kilifi, and compared them to values for Anopheles arabiensis and Anopheles merus at the same location, and for An. gambiae in a location 200 km from Kilifi. In the first simulations ρ changed more rapidly after a population crash than the other statistics, and therefore is a more sensitive indicator of recent population decline. In the empirical data, linkage disequilibrium extends 100-1000 times further, and ρ is 100-1000 times smaller, for the Kilifi population of An. gambiae than for any of the other populations. There were also significant runs of homozygosity in many of the individual An. gambiae mosquitoes from Kilifi. These results support the hypothesis that the recent decline in An. gambiae was driven by the rollout of bed nets. Measuring population genomic parameters in a small sample of individuals before, during and after vector or pest control may be a valuable method of tracking the effectiveness of interventions

An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al